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Evaluating the Safety and Efficacy of Romidepsin in Combination With Antiretroviral Therapy in HIV-Infected Adults With Suppressed Viral Load

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ClinicalTrials.gov Identifier: NCT01933594
Recruitment Status : Completed
First Posted : September 2, 2013
Results First Posted : May 23, 2019
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: Romidepsin
Drug: Placebo for Romidepsin
Enrollment 59
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1-Arm 1A (Romidepsin) Cohort 2-Arm 2A (Romidepsin) Cohort 3-Arm 3A (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin) Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description Participants in Cohort 1, Arm 1A received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohort 2, Arm 2A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohort 3, Arm 3A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohorts 1-3, received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits. Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Period Title: Overall Study
Started 12 12 12 7 13 3
Completed 11 12 12 7 11 3
Not Completed 1 0 0 0 2 0
Reason Not Completed
Lost to Follow-up             1             0             0             0             1             0
Ineligible for subsequent study step             0             0             0             0             1             0
Arm/Group Title Cohort 1-Arm 1A (Romidepsin) Cohort 2-Arm 2A (Romidepsin) Cohort 3-Arm 3A (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin) Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin) Total
Hide Arm/Group Description Participants in Cohort 1, Arm 1A received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohort 2, Arm 2A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohort 3, Arm 3A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits. Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits. Total of all reporting groups
Overall Number of Baseline Participants 12 12 12 7 13 3 59
Hide Baseline Analysis Population Description
All enrolled participants. The placebo arms of Cohorts 1-3 were combined for the Baseline Characteristics.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 7 participants 13 participants 3 participants 59 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
12
 100.0%
12
 100.0%
11
  91.7%
6
  85.7%
11
  84.6%
3
 100.0%
55
  93.2%
>=65 years
0
   0.0%
0
   0.0%
1
   8.3%
1
  14.3%
2
  15.4%
0
   0.0%
4
   6.8%
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 12 participants 7 participants 13 participants 3 participants 59 participants
50
(29 to 54)
52
(44 to 54)
51
(37 to 58)
51
(44 to 56)
56
(48 to 61)
45
(34 to 53)
52
(41 to 57)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 7 participants 13 participants 3 participants 59 participants
Female
1
   8.3%
1
   8.3%
1
   8.3%
0
   0.0%
4
  30.8%
1
  33.3%
8
  13.6%
Male
11
  91.7%
11
  91.7%
11
  91.7%
7
 100.0%
9
  69.2%
2
  66.7%
51
  86.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White non-Hispanic Number Analyzed 12 participants 12 participants 12 participants 7 participants 13 participants 3 participants 59 participants
8
  66.7%
8
  66.7%
6
  50.0%
5
  71.4%
6
  46.2%
2
  66.7%
35
  59.3%
Black non-Hispanic Number Analyzed 12 participants 12 participants 12 participants 7 participants 13 participants 3 participants 59 participants
4
  33.3%
3
  25.0%
5
  41.7%
2
  28.6%
6
  46.2%
1
  33.3%
21
  35.6%
Hispanic (regardless of race) Number Analyzed 12 participants 12 participants 12 participants 7 participants 13 participants 3 participants 59 participants
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
1
   7.7%
0
   0.0%
2
   3.4%
Asian, Pacific Islander Number Analyzed 12 participants 12 participants 12 participants 7 participants 13 participants 3 participants 59 participants
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 12 participants 12 participants 12 participants 7 participants 13 participants 3 participants 59 participants
12
 100.0%
12
 100.0%
12
 100.0%
7
 100.0%
13
 100.0%
3
 100.0%
59
 100.0%
Baseline SCA in Cohorts 1-3   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Log10 copies/mL
Number Analyzed 12 participants 12 participants 12 participants 7 participants 0 participants 0 participants 43 participants
0.08
(-0.13 to 0.32)
-0.2
(-0.49 to 0.02)
0.22
(-0.6 to 0.57)
0.38
(0.22 to 0.51)
NA [3] 
(NA to NA)
[1]
Measure Description: Baseline HIV-1 RNA levels as detected by single copy assay (SCA) was calculated as the average of the pre-entry and entry SCA measurements for Cohorts 1-3
[2]
Measure Analysis Population Description: Cohorts 1-3 were analyzed separately from Cohort 4
[3]
Cohorts 1-3 and Cohort 4 were conducted as separate studies under the same study protocol. As such, all analyses were conducted separately for Cohorts 1-3 and Cohort 4.
Baseline SCA in Cohort 4   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Log10 copies/mL
Number Analyzed 0 participants 0 participants 0 participants 0 participants 13 participants 3 participants 16 participants
-0.2
(-0.7 to 0.39)
-0.25
(-0.25 to 0.31)
NA [3] 
(NA to NA)
[1]
Measure Description: Baseline HIV-1 RNA levels as detected by single copy assay (SCA) was calculated as the average of the pre-entry and entry SCA measurements for Cohort 4
[2]
Measure Analysis Population Description: Cohorts 1-3 were analyzed separately from Cohort 4
[3]
Cohorts 1-3 and Cohort 4 were conducted as separate studies under the same study protocol. As such, all analyses were conducted separately for Cohorts 1-3 and Cohort 4.
Baseline CA RNA in Cohorts 1-3   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Log10 copies/mL
Number Analyzed 12 participants 12 participants 12 participants 7 participants 0 participants 0 participants 43 participants
1.9
(1.7 to 2.6)
2.6
(2.3 to 3)
2.3
(2.0 to 2.7)
2.8
(2.4 to 3)
NA [3] 
(NA to NA)
[1]
Measure Description: Baseline cell-associated HIV-1 RNA levels (CA-RNA) (log10 copies/mL) were measured in resting CD4 T-cells for Cohorts 1-3. Baseline CA-RNA is the pre-entry measurement for Cohorts 1-3.
[2]
Measure Analysis Population Description: Cohorts 1-3 were analyzed separately from Cohort 4
[3]
Cohorts 1-3 and Cohort 4 were conducted as separate studies under the same study protocol. As such, all analyses were conducted separately for Cohorts 1-3 and Cohort 4.
Baseline CA RNA in Cohort 4   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Log10 copies/mL
Number Analyzed 0 participants 0 participants 0 participants 0 participants 13 participants 3 participants 16 participants
1.19
(0.9 to 1.64)
1.61
(1.49 to 2.44)
NA [3] 
(NA to NA)
[1]
Measure Description: Baseline cell-associated HIV-1 RNA levels (CA-RNA) (log10 copies/mL) were measured in PBMCs for Cohort 4. Baseline CA-RNA was calculated as the average of the pre-entry and entry CA-RNA measurement for Cohort 4.
[2]
Measure Analysis Population Description: Cohorts 1-3 were analyzed separately from Cohort 4
[3]
Cohorts 1-3 and Cohort 4 were conducted as separate studies under the same study protocol. As such, all analyses were conducted separately for Cohorts 1-3 and Cohort 4.
1.Primary Outcome
Title Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohorts 1-3 Romidepsin Arms
Hide Description Proportion of participants with Grade 3 or higher adverse events (AEs) in Cohorts 1-3 Romidepsin Arms, including signs/symptoms, lab toxicities, and /or clinical events probably, possibly, or definitely related to study treatment (as judged by the core team, blinded to treatment arm). The DAIDS AE Grading Table (Version 1.0) was used.
Time Frame Measured from the time of Romidepsin administration (at entry) until 28 days after the administration
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohorts 1-3 who received Romidepsin
Arm/Group Title Cohorts 1-3 (Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0
(0 to 0.097)
2.Primary Outcome
Title Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohort 4 Romidepsin Arm
Hide Description Proportion of participants with Grade 3 or Higher Adverse Events (AEs) in Cohort 4 Romidepsin Arm, including signs/symptoms, lab toxicities, and /or clinical events probably, possibly, or definitely related to study treatment (as judged by the core team, blinded to treatment arm). The DAIDS AE Grading Table (Version 1.0) was used.
Time Frame Measured from the time of the first Romidepsin administration through 28 days after the last administration (at day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 4 who received Romidepsin
Arm/Group Title Cohort 4-Arm 4A (Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4 received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.077
(0.002 to 0.36)
3.Primary Outcome
Title Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3
Hide Description

Baseline is defined as the average of the pre-entry and entry values. Hour 24/48 is defined as the average of values at 24 and 48 hours after the single administration of Romidepsin or placebo (at study entry).

Change was calculated as the value at hour 24/48 minus the value at baseline.
Time Frame Pre-entry, entry, 24 and 48 hours after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: log10 copies/mL
0.12
(-0.18 to 0.42)
0.12
(-0.24 to 0.67)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4
Hide Description Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) minus the value at baseline.
Time Frame Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: log10 copies/mL
Change from baseline to 24 hours post infusion 1 Number Analyzed 12 participants 3 participants
0
(-0.32 to 0.23)
-0.11
(-0.45 to 0.55)
Change from baseline to 24 hours post infusion 2 Number Analyzed 12 participants 3 participants
0.03
(-0.03 to 0.53)
0.15
(-0.23 to 1.24)
Change from baseline to 24 hours post infusion 3 Number Analyzed 11 participants 3 participants
0.3
(0 to 0.45)
0.47
(0.33 to 0.63)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 3 participants
0
(-0.17 to 0.23)
0.33
(0.15 to 0.33)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.74
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Primary Outcome
Title Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T-cells in Cohorts 1-3
Hide Description Baseline is defined as the pre-entry value. Change was calculated as the value at 24 hours after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Time Frame Pre-entry and 24 hours after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: log10 (copies/10^6 resting CD4 cells)
-.009
(-0.38 to 0.26)
0
(-0.22 to 0.36)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Primary Outcome
Title Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4
Hide Description Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) minus the value at baseline.
Time Frame Pre-entry, entry and 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: log10 (copies/10^6 PBMCs)
Change from baseline to 24 hours post infusion 1 Number Analyzed 13 participants 3 participants
-0.06
(-0.14 to 0.07)
-0.16
(-0.36 to 0.43)
Change from baseline to 24 hours post infusion 2 Number Analyzed 12 participants 3 participants
-0.07
(-0.38 to 0.31)
-0.52
(-0.91 to -0.15)
Change from baseline to 24 hours post infusion 3 Number Analyzed 11 participants 3 participants
-0.44
(-0.69 to -0.15)
-0.02
(-1.25 to 0.04)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 2 participants
-0.05
(-0.2 to 0.01)
-0.3
(-0.76 to 0.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.92
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3
Hide Description Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 6 hours, 12 hours, 7 days, 14 days and 28 days after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Time Frame Pre-entry, entry, 6 hours, 12 hours, 7 days, 14 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: log10 copies/mL
Change from baseline to 6 hours post infusion Number Analyzed 35 participants 7 participants
-0.02
(-0.38 to 0.22)
0.14
(-0.37 to 0.48)
Change from baseline to 12 hours post infusion Number Analyzed 35 participants 7 participants
0
(-0.49 to 0.2)
0.27
(0.14 to 0.57)
Change from baseline to 7 days post infusion Number Analyzed 36 participants 7 participants
0
(-0.25 to 0.39)
0.27
(-0.16 to 0.63)
Change from baseline to 14 days post infusion Number Analyzed 34 participants 7 participants
0
(-0.2 to 0.15)
-0.13
(-0.39 to 0.27)
Change from baseline to 28 days post infusion Number Analyzed 35 participants 7 participants
0
(-0.3 to 0.3)
-0.08
(-0.3 to 0.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 6 hours post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.44
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 12 hours post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 7 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 14 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 28 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4
Hide Description Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 72 hours after the second administration of Romidepsin or placebo (at day 14) minus the value at baseline.
Time Frame Pre-entry, entry and 72 hours after the second administration of Romidepsin or placebo (at day 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 12 3
Median (Inter-Quartile Range)
Unit of Measure: log10 copies/mL
0
(-0.54 to 0.1)
0.82
(0.15 to 0.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T Cells in Cohorts 1-3
Hide Description Baseline is defined as the pre-entry value. Change was calculated as the value at 14 days after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Time Frame Pre-entry and 14 days after the administration of RMD or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 34 7
Median (Inter-Quartile Range)
Unit of Measure: log10 copies/mL
0.02
(-0.42 to 0.31)
-0.05
(-0.38 to 0.46)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4
Hide Description Baseline is defined as the pre-entry value. Change was calculated as the value at 72 hours after the second administration of Romidepsin or placebo (at day 14) minus the value at baseline.
Time Frame Pre-entry and 72 hours after the second administration of Romidepsin or placebo (at day 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 12 3
Median (Inter-Quartile Range)
Unit of Measure: log10 copies/mL
-0.26
(-0.48 to 0.17)
-0.16
(-0.25 to 0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Histone Acetylation (Median FITC Ac-Histone) in CD3+ Cells in Cohorts 1-3
Hide Description

Baseline is defined as the value at Hour 0, right before the single administration of Romidepsin or placebo.

Change was calculated as the value at 24 hours after administration of Romidepsin or placebo (at entry) minus the value at baseline.

Median Fluorescent Intensity (MFI) data describes a shift in the expression of a fluorescently labeled marker on a population of cells. The reported MFI is an arbitrary value dependent on the voltage applied to the corresponding flow cytometer detector.
Time Frame Hour 0 and 24 hours after the single administration of RMD or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 32 6
Median (Inter-Quartile Range)
Unit of Measure: arbitrary units
-7
(-969 to 1606)
-194
(-1529 to 1343)
12.Secondary Outcome
Title Change From Baseline in Histone Acetylation in (Median FITC Ac-histone) in CD3+ Cells in Cohort 4
Hide Description

Baseline is defined as the value right before the first administration of Romidepsin or placebo (at entry).

Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration minus the value at baseline.

Median Fluorescent Intensity (MFI) data describes a shift in the expression of a fluorescently labeled marker on a population of cells. The reported MFI is an arbitrary value dependent on the voltage applied to the corresponding flow cytometer detector.
Time Frame Entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42), and 72 hours after the second administration (at day 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: arbitrary units
Change from baseline to 24 hours post infusion 1 Number Analyzed 13 participants 3 participants
2402
(1257 to 3821)
749
(-129 to 1498)
Change from baseline to 24 hours post infusion 2 Number Analyzed 12 participants 3 participants
2774
(1467 to 5086)
8497
(696 to 8684)
Change from baseline to 72 hours post infusion 2 Number Analyzed 10 participants 3 participants
4741
(3065 to 8518)
4741
(2479 to 13283)
Change from baseline to 24 hours post infusion 3 Number Analyzed 11 participants 3 participants
4522
(2388 to 8763)
5665
(1041 to 7154)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 3 participants
4342
(3101 to 26464)
2697
(937 to 4022)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 72 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Total HIV-1 DNA in Resting or Total CD4 T Cells in Cohorts 1-3
Hide Description Baseline is defined as the pre-entry value. Change was calculated as the value at 24 hours and 14 days after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Time Frame Pre-entry, 24 hours and 14 days after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: log10 (copies/10^6 resting CD4 cells)
Change from baseline to 24 hours post infusion Number Analyzed 36 participants 7 participants
-0.04
(-0.18 to 0.06)
0.05
(-0.41 to 0.19)
Change from baseline to 14 days post infusion Number Analyzed 34 participants 7 participants
-0.01
(-0.21 to 0.06)
-0.05
(-0.24 to 0.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 14 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Total HIV-1 DNA in PBMCs in Cohort 4
Hide Description Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration minus the value at baseline.
Time Frame Pre-entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: log10 (copies/10^6 PBMCs)
Change from baseline to 24 hours post infusion 1 Number Analyzed 13 participants 3 participants
-0.06
(-0.1 to -0.03)
-0.04
(-0.26 to 0.03)
Change from baseline to 24 hours post infusion 2 Number Analyzed 12 participants 3 participants
-0.13
(-0.22 to -0.04)
-0.11
(-0.12 to -0.06)
Change from baseline to 72 hours post infusion 2 Number Analyzed 12 participants 3 participants
-0.13
(-0.25 to -0.05)
-0.07
(-0.25 to -0.04)
Change from baseline to 24 hours post infusion 3 Number Analyzed 11 participants 3 participants
-0.06
(-0.46 to -0.03)
-0.13
(-0.14 to -0.07)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 2 participants
-0.14
(-0.28 to -0.02)
-0.07
(-0.1 to -0.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 72 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
15.Secondary Outcome
Title PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Efavirenz, Dolutegravir, or Raltegravir) in Cohorts 1-3
Hide Description

Hour 0 is right before the single administration of Romidepsin or placebo (at entry).

Hour 4 is at the completion of Romidepsin or placebo administration. Hours 6, 12 and 24 are 2, 8 and 20 hours after the completion of Romidepsin or placebo administration.

PK concentration (ng/mL) for Romidepsin at hours 0, 4, 6, 12 and 24. PK concentration (ng/mL) for co-administered antiretroviral drugs (Efavirenz [EFV], Dolutegravir [DTG], or Raltegravir [RAL]) at hours 0 and 24.
Time Frame At hours 0, 4, 6, 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
For Romidepsin PK parameters: Cohorts 1-3 participants who received Romidepsin. For co-administered antiretroviral drugs PK parameters: Cohorts 1-3 participants.
Arm/Group Title Cohort 1-Arm 1A (Romidepsin) Cohort 2-Arm 2A (Romidepsin) Cohort 3-Arm 3A (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 1, Arm 1A received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohort 2, Arm 2A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohort 3, Arm 3A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3, received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 12 12 12 7
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
RMD PK concentration at Hour 0 Number Analyzed 12 participants 12 participants 12 participants 0 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
RMD PK concentration at Hour 4 Number Analyzed 12 participants 12 participants 12 participants 0 participants
12
(6.6 to 16.7)
75.2
(54.1 to 84)
89
(53.3 to 127.5)
RMD PK concentration at Hour 6 Number Analyzed 1 participants 11 participants 12 participants 0 participants
3.2
(3.2 to 3.2)
2.7
(1.7 to 4.2)
2.6
(2 to 5)
RMD PK concentration at Hour 12 Number Analyzed 12 participants 12 participants 12 participants 0 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
RMD PK concentration at Hour 24 Number Analyzed 12 participants 12 participants 12 participants 0 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
EFV PK concentration at Hour 0 Number Analyzed 8 participants 5 participants 9 participants 3 participants
2030
(1570 to 3750)
2560
(2490 to 2640)
2612
(1995 to 3423)
2520
(2000 to 2758)
EFV PK concentration at Hour 24 Number Analyzed 8 participants 5 participants 9 participants 3 participants
2105
(1665 to 3405)
1870
(1700 to 2390)
2886
(2262 to 4016)
1600
(1530 to 1849)
RAL PK concentration at Hour 0 Number Analyzed 4 participants 5 participants 0 participants 3 participants
777
(294 to 1990)
910
(845 to 939)
401
(267 to 726)
RAL PK concentration at Hour 24 Number Analyzed 4 participants 5 participants 0 participants 4 participants
1234
(526 to 3475)
398
(348 to 558)
142
(65 to 390)
DTG PK concentration at Hour 0 Number Analyzed 0 participants 2 participants 3 participants 0 participants
4035
(2740 to 5330)
2988
(2163 to 7867)
DTG PK concentration at Hour 24 Number Analyzed 0 participants 2 participants 2 participants 0 participants
2190
(1010 to 3370)
2399
(1181 to 3618)
[1]
All 12 participants had concentration <= BQL (below quantifiable limit)
16.Secondary Outcome
Title PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Dolutegravir or Raltegravi) in Cohort 4
Hide Description

PK concentration (ng/mL) for Romidepsin pre and post the third and fourth administrations of Romidepsin or placebo.

PK concentration (ng/mL) for co-administered antiretroviral drugs (Dolutegravir [DTG], or Raltegravir [RAL]) 24 hours after the third and fourth administrations of Romidepsin or placebo.
Time Frame Pre, post and 24 hours after the third and fourth administrations of Romidepsin or placebo (at days 28 and 42)
Hide Outcome Measure Data
Hide Analysis Population Description

For Romidepsin PK parameters: Cohort 4 participants who received the third and fourth Romidepsin infusion.

For co-administered antiretroviral drugs PK parameters: Cohort 4 participants who received the third and fourth Romidepsin or placebo infusion.
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
RMD PK concentration pre infusion 3 Number Analyzed 1 participants 0 participants
207
(207 to 207)
RMD PK concentration post infusion 3 Number Analyzed 9 participants 0 participants
69
(64 to 164)
RMD PK concentration pre infusion 4 Number Analyzed 11 participants 0 participants
NA [1] 
(NA to NA)
RMD PK concentration post infusion 4 Number Analyzed 8 participants 0 participants
134
(84 to 211)
RAL PK concentration 24 hours post infusion 3 Number Analyzed 4 participants 0 participants
906
(119 to 3420)
RAL PK concentration 24 hours post infusion 4 Number Analyzed 4 participants 0 participants
567
(75 to 2711)
DTG PK concentration 24 hours post infusion 3 Number Analyzed 7 participants 3 participants
2124
(1147 to 3865)
913
(274 to 1128)
DTG PK concentration 24 hours post infusion 4 Number Analyzed 7 participants 3 participants
1568
(985 to 2779)
833
(274 to 1323)
[1]
All 11 participants had concentration <= BQL (below quantifiable limit)
17.Secondary Outcome
Title HIV-1 RNA Levels in Cohorts 1-3
Hide Description HIV-1 RNA levels at 7 days after the single administration of Romidepsin or placebo (at entry)
Time Frame 7 days after the administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants
Arm/Group Title Cohort 1-Arm 1A (Romidepsin) Cohort 2-Arm 2A (Romidepsin) Cohort 3-Arm 3A (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 1, Arm 1A received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohort 2, Arm 2A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohort 3, Arm 3A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3, received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 12 12 12 7
Measure Type: Count of Participants
Unit of Measure: Participants
< 40 copies/mL
11
  91.7%
12
 100.0%
12
 100.0%
7
 100.0%
40-199 copies/mL
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
18.Secondary Outcome
Title HIV-1 RNA Levels in Cohort 4
Hide Description HIV-1 RNA levels at 7 days after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Time Frame 7 days after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Measure Type: Count of Participants
Unit of Measure: Participants
HIV-1 RNA level at day 7 post infusion 1 Number Analyzed 13 participants 2 participants
< 40 copies/mL
13
 100.0%
2
 100.0%
40 - 199 copies/mL
0
   0.0%
0
   0.0%
HIV-1 RNA level at day 7 post infusion 2 Number Analyzed 8 participants 3 participants
< 40 copies/mL
8
 100.0%
3
 100.0%
40 - 199 copies/mL
0
   0.0%
0
   0.0%
HIV-1 RNA level at day 7 post infusion 3 Number Analyzed 11 participants 3 participants
< 40 copies/mL
11
 100.0%
3
 100.0%
40 - 199 copies/mL
0
   0.0%
0
   0.0%
HIV-1 RNA level at day 7 post infusion 4 Number Analyzed 11 participants 3 participants
< 40 copies/mL
11
 100.0%
3
 100.0%
40 - 199 copies/mL
0
   0.0%
0
   0.0%
19.Secondary Outcome
Title Number of Participants With Reported Grade 2-4 AEs in Cohorts 1-3
Hide Description Number of participants with reported grade 2-4 adverse events including signs/symptoms, lab toxicities, and clinical events that are at least possibly related to study treatment. The DAIDS AE Grading Table (Version 1.0) was used.
Time Frame Measured from study entry to off study
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants
Arm/Group Title Cohort 1-Arm 1A (Romidepsin) Cohort 2-Arm 2A (Romidepsin) Cohort 3-Arm 3A (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 1, Arm 1A received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohort 2, Arm 2A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohort 3, Arm 3A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3, received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 12 12 12 7
Measure Type: Count of Participants
Unit of Measure: Participants
4
  33.3%
2
  16.7%
1
   8.3%
1
  14.3%
20.Secondary Outcome
Title Number of Participants With Reported Grade 2-4 AEs in Cohort 4
Hide Description Number of participants with reported grade 2-4 adverse events including signs/symptoms, lab toxicities, and clinical events that are at least possibly related to study treatment. The DAIDS AE Grading Table (Version 1.0) was used.
Time Frame Measured from study entry to off study
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Measure Type: Count of Participants
Unit of Measure: Participants
5
  38.5%
0
   0.0%
21.Secondary Outcome
Title Change From Baseline in CD4+ and CD8+ T Cell Percent in Cohorts 1-3
Hide Description Change in CD4+ and CD8+T cell percent from baseline to after the single administration of Romidepsin or placebo
Time Frame Measured through participant's last study visit
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants did not have CD4+ and CD8+ T cell percent collected
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
22.Secondary Outcome
Title Change From Baseline in CD4+ T Cell Percent in Cohort 4
Hide Description Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours post each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 2, 5, 10 and 18 weeks post the fourth administration minus the value at baseline
Time Frame Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42), and 2, 5, 10 and 18 weeks after the fourth administration (at day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to 24 hours post infusion 1 Number Analyzed 13 participants 3 participants
-2.5
(-3.5 to -0.5)
-2
(-2 to 2.5)
Change from baseline to 24 hours post infusion 2 Number Analyzed 12 participants 3 participants
-4.5
(-5.9 to -2.4)
0.5
(-1 to 2)
Change from baseline to 24 hours post infusion 3 Number Analyzed 11 participants 3 participants
-3.5
(-6.5 to -2.5)
1
(-0.5 to 3)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 3 participants
-4.5
(-7.5 to -2.5)
0.5
(0 to 3)
Change from baseline to 2 weeks post infusion 4 Number Analyzed 11 participants 3 participants
-0.5
(-4.8 to 0.5)
-0.5
(-1 to 2)
Change from baseline to 5 weeks post infusion 4 Number Analyzed 11 participants 3 participants
-1.8
(-3 to -0.4)
0
(-2.5 to 0)
Change from baseline to 10 weeks post infusion 4 Number Analyzed 11 participants 3 participants
-2.8
(-3.5 to -1.5)
-0.5
(-4 to 2)
Change from baseline to 18 weeks post infusion 4 Number Analyzed 11 participants 3 participants
-0.5
(-3.2 to 1.1)
-2.5
(-6 to 1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 2 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.55
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 5 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 10 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 18 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline in CD8+ T Cell Percent in Cohort 4
Hide Description Change in CD8+ T cell percent from baseline to after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Time Frame Measured through 28 days after the single administration of RMD or placebo (at entry, and days 14, 28 and 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants did not have CD8+ T cell percent collected
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
24.Secondary Outcome
Title Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohorts 1-3
Hide Description

Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).

Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo minus the value at baseline.
Time Frame Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to 48 hours post infusion Number Analyzed 35 participants 7 participants
0.5
(-0.3 to 1.8)
0.4
(-1.2 to 2.8)
Change from baseline to 7 days post infusion Number Analyzed 36 participants 7 participants
1
(-0.1 to 2.7)
-1
(-2 to 0.8)
Change from baseline to 28 days post infusion Number Analyzed 34 participants 7 participants
1.2
(-3.2 to 2.6)
-1.4
(-2.4 to 0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 48 hours post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.95
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 7 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 28 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
25.Secondary Outcome
Title Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohorts 1-3
Hide Description

Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).

Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo minus the value at baseline.
Time Frame Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD8 cells
Change from baseline to 48 hours post infusion Number Analyzed 35 participants 7 participants
0.1
(-1.2 to 1.8)
0.3
(-0.9 to 1.3)
Change from baseline to 7 days post infusion Number Analyzed 36 participants 7 participants
0.8
(-0.8 to 3)
-1.3
(-2 to -0.4)
Change from baseline to 28 days post infusion Number Analyzed 34 participants 7 participants
0.3
(-4.2 to 3.1)
-0.1
(-2.7 to 2.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 48 hours post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.89
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 7 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 28 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.74
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
26.Secondary Outcome
Title Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohorts 1-3
Hide Description

Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).

Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo minus the value at baseline.
Time Frame Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to 48 hours post infusion Number Analyzed 35 participants 7 participants
0
(-0.1 to 0.2)
0
(-0.1 to 0.2)
Change from baseline to 7 days post infusion Number Analyzed 36 participants 7 participants
0
(-0.1 to 0.3)
0
(-0.1 to 0.4)
Change from baseline to 28 days post infusion Number Analyzed 34 participants 7 participants
0
(-0.1 to 0.1)
0
(0 to 0.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 48 hours post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 7 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 28 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.38
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
27.Secondary Outcome
Title Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohorts 1-3
Hide Description

Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).

Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo minus the value at baseline.
Time Frame Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD8 cells
Change from baseline to 48 hours post infusion Number Analyzed 35 participants 7 participants
0
(0 to 0.1)
0
(-0.1 to 0.1)
Change from baseline to 7 days post infusion Number Analyzed 36 participants 7 participants
0
(-0.1 to 0.1)
0
(-0.1 to 0.1)
Change from baseline to 28 days post infusion Number Analyzed 34 participants 7 participants
0
(-0.1 to 0.1)
0
(-0.1 to 0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 48 hours post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 7 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.92
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 28 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
28.Secondary Outcome
Title Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohort 4
Hide Description Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at entry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Time Frame Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to 24 hours post infusion 1 Number Analyzed 12 participants 3 participants
0.2
(-0.1 to 1.2)
0.5
(-1.4 to 1.1)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 2 participants
1
(0.4 to 3.5)
2
(1.6 to 2.3)
Change from baseline to 10 weeks post infusion 4 Number Analyzed 10 participants 3 participants
0.4
(-0.5 to 1.3)
0.7
(0.6 to 2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 10 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
29.Secondary Outcome
Title Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohort 4
Hide Description Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at entry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Time Frame Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD8 cells
Change from baseline to 24 hours post infusion 1 Number Analyzed 12 participants 3 participants
0.6
(-0.2 to 1.8)
0.2
(-0.2 to 0.2)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 2 participants
1.1
(-0.5 to 2.1)
1.1
(-0.3 to 2.4)
Change from baseline to 10 weeks post infusion 4 Number Analyzed 10 participants 3 participants
-0.3
(-2.8 to 0.4)
2.8
(1.6 to 8.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments hange from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 10 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.028
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
30.Secondary Outcome
Title Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohort 4
Hide Description Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at etnry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Time Frame Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at etnry and day 42), and 10 weeks after the fourth administration (at day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to 24 hours post infusion 1 Number Analyzed 12 participants 3 participants
0
(0 to 0.1)
-0.1
(-0.1 to 0.1)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 2 participants
0
(0 to 0.4)
-0.1
(-0.1 to 0)
Change from baseline to 10 weeks post infusion 4 Number Analyzed 10 participants 3 participants
0
(-0.2 to 0.5)
-0.1
(-0.1 to 0.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 10 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
31.Secondary Outcome
Title Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohort 4
Hide Description Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at etnry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Time Frame Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at etnry and day 42), and 10 weeks after the fourth administration (at day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD8 cells
Change from baseline to 24 hours post infusion 1 Number Analyzed 12 participants 3 participants
0
(0 to 0.1)
0
(-0.1 to 0)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 2 participants
0
(0 to 0.1)
-0.1
(-0.2 to 0)
Change from baseline to 10 weeks post infusion 4 Number Analyzed 10 participants 3 participants
0
(0 to 0.1)
0
(-0.2 to 0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 10 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
32.Secondary Outcome
Title Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3
Hide Description

Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).

Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry) minus the value at baseline.
Time Frame Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to 48 hours post infusion Number Analyzed 35 participants 7 participants
0.2
(-0.6 to 1)
1.2
(0.1 to 7)
Change from baseline to 7 days post infusion Number Analyzed 36 participants 7 participants
0.6
(-1.2 to 2)
0
(-3.7 to 0.3)
Change from baseline to 28 days post infusion Number Analyzed 35 participants 7 participants
1.2
(0.1 to 3.9)
-1.3
(-3.6 to 0.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 48 hours post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 7 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 28 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.031
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
33.Secondary Outcome
Title Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3
Hide Description

Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).

Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry) minus the value at baseline.
Time Frame Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD8 cells
Change from baseline to 48 hours post infusion Number Analyzed 35 participants 7 participants
-0.1
(-2.1 to 0.6)
1.8
(-1 to 4.3)
Change from baseline to 7 days post infusion Number Analyzed 36 participants 7 participants
0.3
(-1.4 to 3.1)
-1.1
(-4.6 to 3.3)
Change from baseline to 28 days post infusion Number Analyzed 35 participants 7 participants
0.9
(-1.7 to 3)
-1.9
(-4.1 to 2.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 48 hours post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 7 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change from baseline to 28 days post infusion
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
34.Secondary Outcome
Title Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4
Hide Description Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at entry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Time Frame Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to 24 hours post infusion 1 Number Analyzed 13 participants 3 participants
0.5
(-2.7 to 1.3)
-1.4
(-2.2 to 7)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 3 participants
-2
(-4.5 to 3.1)
0.9
(-0.7 to 2.4)
Change from baseline to 10 weeks post infusion 4 Number Analyzed 10 participants 3 participants
0.3
(-2.9 to 1.5)
0.1
(-3.7 to 5.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 10 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
35.Secondary Outcome
Title Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4
Hide Description Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at entry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Time Frame Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD8 cells
Change from baseline to 24 hours post infusion 1 Number Analyzed 13 participants 3 participants
0.1
(-3.7 to 1.3)
-4.1
(-5.1 to 8)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 3 participants
-2.5
(-3.3 to 15.4)
-.6
(-1.5 to 0.3)
Change from baseline to 10 weeks post infusion 4 Number Analyzed 10 participants 3 participants
0.9
(-4.1 to 4.3)
-0.8
(-6.5 to 10.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 10 weeks post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
36.Secondary Outcome
Title Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD4+ T-cells in Cohorts 1-3
Hide Description

Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).

Change was calculated as the value at 24 hours after the single administration of Romidepsin or placebo (at entry) minus the value at baseline.
Time Frame Hour 0 and 24 hours after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change in pNFKB+% on CD4 Number Analyzed 35 participants 7 participants
20
(9.4 to 35.1)
19.3
(2.4 to 39.1)
Change in pS175% on CD4 Number Analyzed 35 participants 7 participants
18.1
(8.5 to 28.3)
6
(-3.5 to 31.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change in pNFKB+% on CD4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change in pS175% on CD4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.27
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
37.Secondary Outcome
Title Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD8+ T-cells in Cohorts 1-3
Hide Description

Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).

Change was calculated as the value at 24 hours after the single administration of Romidepsin or placebo (at entry) minus the value at baseline.
Time Frame Hour 0 and 24 hours after the single administration of Romidepsin or placebo (at entry)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohorts 1-3 participants with available data
Arm/Group Title Cohorts 1-3 (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohorts 1-3 who received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit.
Overall Number of Participants Analyzed 36 7
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD8 cells
Change in pNFKB+% on CD8 Number Analyzed 35 participants 7 participants
16.5
(1.4 to 29)
3.8
(-8.3 to 29.9)
Change in pS175% on CD8 Number Analyzed 35 participants 7 participants
26.5
(18.1 to 38.8)
25.3
(14.9 to 37.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change in pNFKB+% on CD8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
Comments Change in pS175% on CD8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
38.Secondary Outcome
Title Change From Baseline in PTEF-b Phosphorylation (pNFKB+%) in CD4+ T-cells in Cohort 4
Hide Description Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14) minus the value at baseline.
Time Frame Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to 24 hours post infusion 1 Number Analyzed 13 participants 3 participants
5.04
(0 to 8.63)
0.01
(0 to 0.01)
Change from baseline to 24 hours post infusion 2 Number Analyzed 12 participants 3 participants
8.78
(4.77 to 13.69)
0
(0 to 0.03)
Change from baseline to 72 hours post infusion 2 Number Analyzed 12 participants 3 participants
6.39
(0 to 9.83)
0
(0 to 0.02)
Change from baseline to 24 hours post infusion 3 Number Analyzed 11 participants 3 participants
5.78
(0.02 to 11.22)
0
(0 to 0.08)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 2 participants
9.63
(4.95 to 11.74)
0
(-0.01 to 0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 72 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
39.Secondary Outcome
Title Change From Baseline in PTEF-b Phosphorylation (pS175+%) in CD4+ T-cells in Cohort 4
Hide Description Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14) minus the value at baseline.
Time Frame Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort 4 participants with available data
Arm/Group Title Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description:
Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
Overall Number of Participants Analyzed 13 3
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to 24 hours post infusion 1 Number Analyzed 13 participants 3 participants
9.93
(0.01 to 17.06)
-0.01
(-0.01 to 0.01)
Change from baseline to 24 hours post infusion 2 Number Analyzed 12 participants 3 participants
17
(12.87 to 18.66)
-0.01
(-0.01 to 0)
Change from baseline to 72 hours post infusion 2 Number Analyzed 12 participants 3 participants
11
(0.01 to 15.36)
-0.01
(-0.01 to 0)
Change from baseline to 24 hours post infusion 3 Number Analyzed 11 participants 3 participants
14.85
(5.29 to 15.58)
0
(-0.01 to 0.05)
Change from baseline to 24 hours post infusion 4 Number Analyzed 11 participants 2 participants
16.52
(6.82 to 18.21)
0.01
(0 to 0.02)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 72 hours post infusion 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 4-Arm 4A (Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin)
Comments Change from baseline to 24 hours post infusion 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame Adverse event data were collected from study entry until the end of study (28 days for Cohorts 1-3 and up to 48 weeks for Cohort 4).
Adverse Event Reporting Description The protocol required reporting of all diagnoses, all signs/symptoms/laboratory values Grade ≥ 2, and all signs/symptoms/laboratory values that led to treatment change and/or Grade ≥ 3 and/or met EAE or ICH reporting requirements. For grading, sites referred to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009), http://rsc.tech-res.com/clinical-research-sites/safety-reporting.
 
Arm/Group Title Cohort 1-Arm 1A (Romidepsin) Cohort 2-Arm 2A (Romidepsin) Cohort 3-Arm 3A (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin) Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Hide Arm/Group Description Participants in Cohort 1, Arm 1A received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohort 2, Arm 2A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohort 3, Arm 3A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohorts 1-3 who received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits. Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits.
All-Cause Mortality
Cohort 1-Arm 1A (Romidepsin) Cohort 2-Arm 2A (Romidepsin) Cohort 3-Arm 3A (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin) Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/12 (0.00%)   0/12 (0.00%)   0/7 (0.00%)   0/13 (0.00%)   0/3 (0.00%) 
Hide Serious Adverse Events
Cohort 1-Arm 1A (Romidepsin) Cohort 2-Arm 2A (Romidepsin) Cohort 3-Arm 3A (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin) Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/12 (0.00%)   0/12 (0.00%)   0/7 (0.00%)   0/13 (0.00%)   1/3 (33.33%) 
Infections and infestations             
Abdominal wall abscess † 1  0/12 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/7 (0.00%)  0/13 (0.00%)  1/3 (33.33%) 
1
Term from vocabulary, MedDRA 21.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1-Arm 1A (Romidepsin) Cohort 2-Arm 2A (Romidepsin) Cohort 3-Arm 3A (Romidepsin) Cohorts 1-3 (Placebo for Romidepsin) Cohort 4-Arm 4A (Romidepsin) Cohort 4-Arm 4B (Placebo for Romidepsin)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/12 (66.67%)   6/12 (50.00%)   1/12 (8.33%)   3/7 (42.86%)   9/13 (69.23%)   2/3 (66.67%) 
Blood and lymphatic system disorders             
Iron deficiency anaemia † 1  0/12 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/7 (0.00%)  0/13 (0.00%)  1/3 (33.33%) 
Cardiac disorders             
Bradycardia † 1  0/12 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/7 (14.29%)  0/13 (0.00%)  0/3 (0.00%) 
Ear and labyrinth disorders             
Deafness † 1  0/12 (0.00%)  1/12 (8.33%)  0/12 (0.00%)  0/7 (0.00%)  0/13 (0.00%)  0/3 (0.00%) 
Tinnitus † 1  0/12 (0.00%)  1/12 (8.33%)  0/12 (0.00%)  0/7 (0.00%)  0/13 (0.00%)  0/3 (0.00%) 
Eye disorders             
Eye discharge † 1  0/12 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  1/7 (14.29%)  0/13 (0.00%)  0/3 (0.00%) 
Vision blurred † 1  0/12 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/7 (0.00%)  1/13 (7.69%)  0/3 (0.00%) 
Gastrointestinal disorders             
Abdominal pain † 1  1/12 (8.33%)  0/12 (0.00%)  0/12 (0.00%)  0/7 (0.00%)  0/13 (0.00%)  1/3 (33.33%) 
Diarrhoea † 1  1/12 (8.33%)  0/12 (0.00%)  0/12 (0.00%)  1/7 (14.29%)  0/13 (0.00%)  0/3 (0.00%) 
Dysphagia † 1  0/12 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/7 (0.00%)  1/13 (7.69%)  0/3 (0.00%) 
Nausea † 1  1/12 (8.33%)  0/12 (0.00%)  0/12 (0.00%)  0/7 (0.00%)  2/13 (15.38%)  0/3 (0.00%) 
Vomiting † 1  0/12 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/7 (0.00%)  1/13 (7.69%)  0/3 (0.00%) 
General disorders             
Fatigue † 1  3/12 (25.00%)  1/12 (8.33%)  0/12 (0.00%)  1/7 (14.29%)  1/13 (7.69%)  0/3 (0.00%) 
Malaise † 1  0/12 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/7 (0.00%)  0/13 (0.00%)  1/3 (33.33%) 
Pyrexia † 1  0/12 (0.00%)  0/12 (0.00%)  0/12 (0.00%)  0/7 (0.00%)  0/13 (0.00%)  2/3 (66.67%) 
Infections and infestations