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CD101 Compared to Caspofungin Followed by Oral Step Down in Subjects With Candidemia and/or Invasive Candidiasis-Bridging Extension (STRIVE)

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ClinicalTrials.gov Identifier: NCT02734862
Recruitment Status : Completed
First Posted : April 12, 2016
Results First Posted : December 8, 2020
Last Update Posted : December 8, 2020
Sponsor:
Information provided by (Responsible Party):
Cidara Therapeutics Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Candidemia
Mycoses
Fungal Infection
Fungemia
Invasive Candidiasis
Interventions Drug: CD101
Drug: Caspofungin
Drug: Fluconazole
Drug: intravenous placebo
Drug: oral placebo
Enrollment 207
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group 1 Group 2 Group 3
Hide Arm/Group Description

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).

After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.

Caspofungin: Intravenous antifungal therapy

Fluconazole: oral antifungal therapy

intravenous placebo: normal saline

Period Title: Part A
Started [1] 35 36 36
Completed 23 28 22
Not Completed 12 8 14
Reason Not Completed
Death             3             4             6
Lost to Follow-up             2             1             1
Withdrawal by Subject             1             1             2
Physician Decision             2             0             1
Adverse Event             2             0             1
Noncompliance             1             1             0
Other             1             1             3
[1]

The Intent-to-Treat (ITT) population analyzed consisted of all subjects randomized to treatment. Subjects were analyzed based on the treatment group to which they were randomized.

In Part A, subjects were randomized in a 1:1:1 ratio to receive rezafungin treatment Group 1, rezafungin Treatment Group 2 (defined below), or IV caspofungin Group 3. Enrollment into Part A closed and Part B began.

Period Title: Part B
Started [1] 46 21 33
Completed 33 14 28
Not Completed 13 7 5
Reason Not Completed
Death             8             3             5
Lost to Follow-up             2             2             0
Withdrawal by Subject             3             1             0
Other             0             1             0
[1]

The Intent-to-Treat (ITT) population analyzed consisted of all subjects randomized to treatment. Subjects were analyzed based on the treatment group to which they were randomized.

In Part B, subjects were randomized 2:1 to receive rezafungin treatment or IV caspofungin.

Arm/Group Title Group 1 Group 2 Group 3 Total
Hide Arm/Group Description

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).

After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.

Caspofungin: Intravenous antifungal therapy

Fluconazole: oral antifungal therapy

intravenous placebo: normal saline

Total of all reporting groups
Overall Number of Baseline Participants 81 57 69 207
Hide Baseline Analysis Population Description
The Intent-to-Treat (ITT) population analyzed consisted of all subjects randomized to treatment. Subjects were analyzed based on the treatment group to which they were randomized.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 57 participants 69 participants 207 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
49
  60.5%
32
  56.1%
40
  58.0%
121
  58.5%
>=65 years
32
  39.5%
25
  43.9%
29
  42.0%
86
  41.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 81 participants 57 participants 69 participants 207 participants
59.4  (15.86) 60.0  (15.90) 59.4  (15.85) 59.6  (15.79)
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 81 participants 57 participants 69 participants 207 participants
61.0
(24.0 to 88.0)
63.0
(24.0 to 91.0)
63.0
(24.0 to 93.0)
62.0
(24.0 to 93.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 57 participants 69 participants 207 participants
Female
37
  45.7%
21
  36.8%
31
  44.9%
89
  43.0%
Male
44
  54.3%
36
  63.2%
38
  55.1%
118
  57.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 57 participants 69 participants 207 participants
Hispanic or Latino
8
   9.9%
9
  15.8%
7
  10.1%
24
  11.6%
Not Hispanic or Latino
73
  90.1%
46
  80.7%
59
  85.5%
178
  86.0%
Unknown or Not Reported
0
   0.0%
2
   3.5%
3
   4.3%
5
   2.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 57 participants 69 participants 207 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   1.8%
3
   4.3%
4
   1.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
8
   9.9%
7
  12.3%
4
   5.8%
19
   9.2%
White
69
  85.2%
44
  77.2%
59
  85.5%
172
  83.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
   4.9%
5
   8.8%
3
   4.3%
12
   5.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Greece Number Analyzed 81 participants 57 participants 69 participants 207 participants
6 6 8 20
Canada Number Analyzed 81 participants 57 participants 69 participants 207 participants
1 1 3 5
Romania Number Analyzed 81 participants 57 participants 69 participants 207 participants
2 0 3 5
Belgium Number Analyzed 81 participants 57 participants 69 participants 207 participants
9 9 12 30
Hungary Number Analyzed 81 participants 57 participants 69 participants 207 participants
2 0 0 2
United States Number Analyzed 81 participants 57 participants 69 participants 207 participants
26 22 23 71
Italy Number Analyzed 81 participants 57 participants 69 participants 207 participants
7 2 5 14
Bulgaria Number Analyzed 81 participants 57 participants 69 participants 207 participants
4 1 2 7
Russia Number Analyzed 81 participants 57 participants 69 participants 207 participants
2 1 0 3
Spain Number Analyzed 81 participants 57 participants 69 participants 207 participants
22 15 13 50
Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 57 participants 69 participants 207 participants
Candidemia
62
  76.5%
46
  80.7%
56
  81.2%
164
  79.2%
Invasive Candidiasis
19
  23.5%
11
  19.3%
13
  18.8%
43
  20.8%
Estimated Normalized Creatinine Clearance   [1] 
Mean (Standard Deviation)
Unit of measure:  mL/min/1.73m^2
Number Analyzed 79 participants 50 participants 64 participants 193 participants
90.8  (52.03) 72.8  (52.14) 87.1  (59.29) 84.9  (54.78)
[1]
Measure Analysis Population Description: Data was not captured at baseline for all subjects, preventing calculation of the normalized creatinine clearance.
Estimated Normalized Creatinine Clearance   [1] 
Median (Full Range)
Unit of measure:  mL/min/1.73m^2
Number Analyzed 79 participants 50 participants 64 participants 193 participants
81.8
(8.1 to 255.4)
57.7
(5.9 to 294.7)
74.4
(7.7 to 278.8)
74.8
(5.9 to 294.7)
[1]
Measure Analysis Population Description: Data was not captured at baseline for all subjects, preventing calculation of the normalized creatinine clearance.
Acute Physiology and Chronic Health Evaluation (APACHE) II Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 79 participants 55 participants 63 participants 197 participants
13.4  (7.13) 14.1  (6.72) 14.0  (7.39) 13.8  (7.07)
[1]
Measure Description:

The APACHE II score is a validated predictor of mortality in critically ill patients. It can be used as a surrogate measure for severity of illness in a patient and can be used in clinical trials at baseline to estimate the overall severity of illness in a patient population.

Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Critical Care Medicine 1985 13(10):818-29.

APACHE II score = acute physiology score + age points + chronic health points. Minimum score = 0; maximum score = 71.

[2]
Measure Analysis Population Description: Data was not captured for all subjects, as some subjects did not have the APACHE II calculation performed.
Acute Physiology and Chronic Health Evaluation (APACHE) II Score   [1] [2] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 79 participants 55 participants 63 participants 197 participants
12.0
(2.0 to 31.0)
14.0
(2.0 to 28.0)
13.0
(1.0 to 35.0)
12.0
(1.0 to 35.0)
[1]
Measure Description:

The APACHE II score is a validated predictor of mortality in critically ill patients. It can be used as a surrogate measure for severity of illness in a patient and can be used in clinical trials at baseline to estimate the overall severity of illness in a patient population.

Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Critical Care Medicine 1985 13(10):818-29.

APACHE II score = acute physiology score + age points + chronic health points. Minimum score = 0; maximum score = 71.

[2]
Measure Analysis Population Description: Data was not captured for all subjects, as some subjects did not have the APACHE II calculation performed.
Acute Physiology and Chronic Health Evaluation (APACHE) II Category   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 57 participants 69 participants 207 participants
0-9
23
  28.4%
15
  26.3%
17
  24.6%
55
  26.6%
10-19
39
  48.1%
26
  45.6%
37
  53.6%
102
  49.3%
≥20
17
  21.0%
14
  24.6%
9
  13.0%
40
  19.3%
Missing
2
   2.5%
2
   3.5%
6
   8.7%
10
   4.8%
[1]
Measure Description:

The APACHE II score is a validated predictor of mortality in critically ill patients. It can be used as a surrogate measure for severity of illness in a patient and can be used in clinical trials at baseline to estimate the overall severity of illness in a patient population.

Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Critical Care Medicine 1985 13(10):818-29.

APACHE II score = acute physiology score + age points + chronic health points. Minimum score = 0; maximum score = 71.

1.Primary Outcome
Title Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]
Hide Description Number of Subjects with Incidence of Treatment Emergent Adverse Events based on clinical chemistry, hematology and urine analysis laboratory test, vital sign, physical exams and ECG abnormalities.
Time Frame From first dose of study drug through Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population includes all subjects randomized to treatment and who received any amount of study drug. A total of 202 subjects were included in the Safety Population.
Arm/Group Title Group 1 Group 2 Group 3
Hide Arm/Group Description:

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).

After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.

Caspofungin: Intravenous antifungal therapy

Fluconazole: oral antifungal therapy

intravenous placebo: normal saline

Overall Number of Participants Analyzed 81 53 68
Measure Type: Count of Participants
Unit of Measure: Participants
71
  87.7%
49
  92.5%
55
  80.9%
2.Primary Outcome
Title Resolution of Systemic Signs Attributable to Candidemia and/or Invasive Candidiasis and Mycological Eradication [Overall Success]
Hide Description Number of subjects with mycological eradication and complete resolution of all systemic signs of candidemia and/or invasive candidiasis which were present at baseline
Time Frame Day 14 (± 1 day)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3
Hide Arm/Group Description:

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).

After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.

Caspofungin: Intravenous antifungal therapy

Fluconazole: oral antifungal therapy

intravenous placebo: normal saline

Overall Number of Participants Analyzed 76 46 61
Measure Type: Count of Participants
Unit of Measure: Participants
46
  60.5%
35
  76.1%
41
  67.2%
3.Secondary Outcome
Title Mycological Eradication and Resolution of Systemic Signs
Hide Description Evaluate overall success signs (mycological eradication and resolution of systemic signs attributable to candidemia and/or IC) in the mITT population.
Time Frame Day 5, and Follow-up (FU Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3
Hide Arm/Group Description:

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).

After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.

Caspofungin: Intravenous antifungal therapy

Fluconazole: oral antifungal therapy

intravenous placebo: normal saline

Overall Number of Participants Analyzed 76 46 61
Measure Type: Count of Participants
Unit of Measure: Participants
Day 5
42
  55.3%
34
  73.9%
34
  55.7%
Follow-up
36
  47.4%
30
  65.2%
36
  59.0%
4.Secondary Outcome
Title Mycological Eradication
Hide Description Evaluate mycological success (eradication) in the mITT population.
Time Frame Day 5, Day 14 (±1 day), and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3
Hide Arm/Group Description:

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).

After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.

Caspofungin: Intravenous antifungal therapy

Fluconazole: oral antifungal therapy

intravenous placebo: normal saline

Overall Number of Participants Analyzed 76 46 61
Measure Type: Count of Participants
Unit of Measure: Participants
Day 5
50
  65.8%
35
  76.1%
38
  62.3%
Day 14
50
  65.8%
35
  76.1%
42
  68.9%
Follow-up
39
  51.3%
30
  65.2%
36
  59.0%
5.Secondary Outcome
Title Clinical Cure
Hide Description

Evaluate clinical cure as assessed by the Investigator in the mITT population. Subjects must meet all of the following requirements:

  • Resolution of attributable systemic signs and symptoms of candidemia/IC that were present at baseline
  • No new systemic signs or symptoms attributable to candidemia/IC
  • No additional systemic antifungal therapy administered for candidemia/IC
  • The subject is alive
Time Frame Day 14 (±1 day) and FU (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia).
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3
Hide Arm/Group Description:

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).

After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.

Caspofungin: Intravenous antifungal therapy

Fluconazole: oral antifungal therapy

intravenous placebo: normal saline

Overall Number of Participants Analyzed 76 46 61
Measure Type: Count of Participants
Unit of Measure: Participants
Day 14
53
  69.7%
37
  80.4%
43
  70.5%
Follow-up
42
  55.3%
32
  69.6%
38
  62.3%
6.Secondary Outcome
Title Evaluate PK (Cmax)
Hide Description Evaluate maximum plasma concentration (Cmax) (Part A only)
Time Frame Day 1, 10 minutes before end of infusion (EOI)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population: all rezafungin-treated subjects from Part A with at least 1 plasma sample obtained for PK analysis.
Arm/Group Title Group 1 Group 2
Hide Arm/Group Description:

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Overall Number of Participants Analyzed 29 30
Mean (Standard Deviation)
Unit of Measure: μg/mL
15.258  (5.5430) 14.743  (5.6450)
7.Secondary Outcome
Title Evaluate PK (Cmin)
Hide Description Evaluate minimum plasma concentration (Cmin) (Part A only)
Time Frame Day 8, predose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population: all rezafungin-treated subjects from Part A with at least 1 plasma sample obtained for PK analysis.
Arm/Group Title Group 1 Group 2
Hide Arm/Group Description:

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Overall Number of Participants Analyzed 25 28
Mean (Standard Deviation)
Unit of Measure: μg/mL
2.050  (0.9767) 2.313  (1.2165)
8.Secondary Outcome
Title Evaluate PK (Cmin)
Hide Description Evaluate minimum plasma concentration (Cmin) (Part A only)
Time Frame Day 15, predose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population: all rezafungin-treated subjects from Part A with at least 1 plasma sample obtained for PK analysis.
Arm/Group Title Group 1 Group 2
Hide Arm/Group Description:

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Overall Number of Participants Analyzed 21 21
Mean (Standard Deviation)
Unit of Measure: μg/mL
3.068  (1.4565) 2.131  (0.8506)
Time Frame Adverse events were collected following the signing of the informed consent at screening and throughout the study until the follow up visit (Days 45-52 for subjects with candidemia only or Days 52-59 for subjects with IC, with or without candidemia).
Adverse Event Reporting Description All-Cause Mortality was assessed in the Intent-to-Treat (ITT) Population. The ITT Population consisted of all subjects randomized to treatment. Serious and Other Adverse Events were assessed in the Safety Population. The Safety Population consisted of all subjects randomized who received any amount of study drug. All safety analyses were performed by actual treatment received.
 
Arm/Group Title Group 1 Group 2 Group 3
Hide Arm/Group Description

Subjects in the CD101 IV treatment group 1 (Part A Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 400 mg on Day 15 (for all subjects) and an optional dose of 400 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the CD101 IV treatment group 2 (Part B Only - up to 30 mITT subjects) will receive CD101 IV 400 mg on Day 1 and Day 8, with an optional dose of 200 mg on Day 15 (for all subjects) and an optional dose of 200 mg on Day 22 (only for subjects with IC), if needed.

Daily intravenous placebo infusion when not administered CD101. Daily oral placebo as step down.

CD101: Intravenous antifungal therapy

intravenous placebo: normal saline

oral placebo: microcrystalline cellulose

Subjects in the caspofungin group will receive IV caspofungin (a single 70 mg loading dose on Day 1 followed by 50 mg once daily) for ≥3 days up to a maximum of 21 days for subjects with candidemia only and up to a maximum of 28 days for subjects with IC (with or without candidemia).

After ≥3 days of IV therapy, subjects in the caspofungin group can be switched to oral step-down therapy of fluconazole (a loading dose of 800 mg [4 capsules] on the first day followed by 400 mg [2 capsules]/day thereafter). After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.

Caspofungin: Intravenous antifungal therapy

Fluconazole: oral antifungal therapy

intravenous placebo: normal saline

All-Cause Mortality
Group 1 Group 2 Group 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/81 (17.28%)   7/57 (12.28%)   13/69 (18.84%) 
Hide Serious Adverse Events
Group 1 Group 2 Group 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   35/81 (43.21%)   28/53 (52.83%)   29/68 (42.65%) 
Blood and lymphatic system disorders       
Disseminated intravascular coagulation   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Haemorrhagic anaemia   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Iron deficiency anaemia   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Sickle cell anaemia with crisis   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Cardiac disorders       
Angina pectoris   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Atrial flutter   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Atrioventricular block   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Bradycardia   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Cardiac arrest   0/81 (0.00%)  1/53 (1.89%)  1/68 (1.47%) 
Cardiac failure   0/81 (0.00%)  1/53 (1.89%)  1/68 (1.47%) 
Right ventricular failure   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Ventricular tachycardia   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Gastrointestinal disorders       
Abdominal pain   0/81 (0.00%)  1/53 (1.89%)  1/68 (1.47%) 
Colonic fistula   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Gastrointestinal haemorrhage   2/81 (2.47%)  1/53 (1.89%)  0/68 (0.00%) 
Haemorrhagic ascites   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Impaired gastric emptying   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Peritoneocutaneous fistula   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Rectal haemorrhage   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Upper gastrointestinal haemorrhage   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Vomiting   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
General disorders       
Generalised oedema   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Multiple organ dysfunction syndrome   2/81 (2.47%)  0/53 (0.00%)  2/68 (2.94%) 
Hepatobiliary disorders       
Biloma   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Drug-induced liver injury   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Infections and infestations       
Abdominal abscess   1/81 (1.23%)  1/53 (1.89%)  0/68 (0.00%) 
Abscess limb   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Bacteraemia   0/81 (0.00%)  2/53 (3.77%)  1/68 (1.47%) 
Bronchitis   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Candida sepsis   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Clostridium difficile colitis   2/81 (2.47%)  0/53 (0.00%)  0/68 (0.00%) 
Diverticulitis   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Endocarditis candida   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Escherichia bacteraemia   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Pelvic abscess   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Peritonitis   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Peritonitis bacterial   2/81 (2.47%)  0/53 (0.00%)  0/68 (0.00%) 
Pneumonia   2/81 (2.47%)  0/53 (0.00%)  1/68 (1.47%) 
Pulmonary sepsis   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Renal abscess   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Sepsis   1/81 (1.23%)  2/53 (3.77%)  2/68 (2.94%) 
Septic embolus   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Septic shock   9/81 (11.11%)  1/53 (1.89%)  2/68 (2.94%) 
Staphylococcal bacteraemia   0/81 (0.00%)  2/53 (3.77%)  0/68 (0.00%) 
Systemic candida   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Urosepsis   1/81 (1.23%)  1/53 (1.89%)  0/68 (0.00%) 
Injury, poisoning and procedural complications       
Fall   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Femur fracture   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Gastrointestinal stoma complication   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Post procedural fistula   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Post procedural haemorrhage   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Tracheal haemorrhage   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Vascular pseudoaneurysm   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Investigations       
Aspiration bronchial   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Metabolism and nutrition disorders       
Diabetes mellitus   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Hyperkalaemia   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Hyponatraemia   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Metabolic acidosis   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Malignant neoplasm progression   2/81 (2.47%)  0/53 (0.00%)  1/68 (1.47%) 
Malignant pleural effusion   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Neoplasm malignant   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Post transplant lymphoproliferative disorder   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Nervous system disorders       
Depressed level of consciousness   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Encephalopathy   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Metabolic encephalopathy   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Neurodegenerative disorder   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Neurological symptom   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Peroneal nerve palsy   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Seizure   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Renal and urinary disorders       
Acute kidney injury   1/81 (1.23%)  1/53 (1.89%)  0/68 (0.00%) 
Haematuria   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory distress syndrome   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Acute respiratory failure   1/81 (1.23%)  0/53 (0.00%)  3/68 (4.41%) 
Apnoea   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Aspiration   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Atelectasis   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Dyspnoea   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Pleural effusion   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Pneumonia aspiration   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Pneumothorax   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Pulmonary embolism   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Respiratory arrest   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Respiratory failure   2/81 (2.47%)  1/53 (1.89%)  1/68 (1.47%) 
Skin and subcutaneous tissue disorders       
Henoch-Schonlein purpura   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Vascular disorders       
Arterial haemorrhage   0/81 (0.00%)  1/53 (1.89%)  0/68 (0.00%) 
Deep vein thrombosis   0/81 (0.00%)  0/53 (0.00%)  1/68 (1.47%) 
Shock   1/81 (1.23%)  0/53 (0.00%)  0/68 (0.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1 Group 2 Group 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   70/81 (86.42%)   49/53 (92.45%)   53/68 (77.94%) 
Blood and lymphatic system disorders       
Anaemia   6/81 (7.41%)  7/53 (13.21%)  4/68 (5.88%) 
Gastrointestinal disorders       
Diarrhoea   7/81 (8.64%)  11/53 (20.75%)  10/68 (14.71%) 
Vomiting   6/81 (7.41%)  8/53 (15.09%)  5/68 (7.35%) 
Nausea   4/81 (4.94%)  8/53 (15.09%)  6/68 (8.82%) 
Abdominal pain   5/81 (6.17%)  5/53 (9.43%)  4/68 (5.88%) 
General disorders       
Pyrexia   9/81 (11.11%)  4/53 (7.55%)  6/68 (8.82%) 
Oedema peripheral   6/81 (7.41%)  2/53 (3.77%)  0/68 (0.00%) 
Metabolism and nutrition disorders       
Hypokalaemia   13/81 (16.05%)  9/53 (16.98%)  9/68 (13.24%) 
Psychiatric disorders       
Insomnia   4/81 (4.94%)  4/53 (7.55%)  2/68 (2.94%) 
Skin and subcutaneous tissue disorders       
Decubitus ulcer   4/81 (4.94%)  3/53 (5.66%)  3/68 (4.41%) 
Vascular disorders       
Hypotension   6/81 (7.41%)  2/53 (3.77%)  4/68 (5.88%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Taylor Sandison, M.D., MPH
Organization: Cidara Therapeutics, Inc.
Phone: 858-888-7868
EMail: clinicaltrialinfo@cidara.com
Layout table for additonal information
Responsible Party: Cidara Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT02734862    
Other Study ID Numbers: CD101.IV.2.03
2015-005599-51 ( EudraCT Number )
First Submitted: March 16, 2016
First Posted: April 12, 2016
Results First Submitted: September 4, 2020
Results First Posted: December 8, 2020
Last Update Posted: December 8, 2020