Safety and Efficacy of Romidepsin and the Therapeutic Vaccine Vacc-4x for Reduction of the Latent HIV‐1 Reservoir (REDUC)

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition:	HIV I Infection
Interventions:	Drug: Romidepsin; Biological: Vacc-4x; Biological: rhuGM-CSF

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First subject screened 6 March 2014 and last subject last visit 25 June 2014 for Part A. First subject screened 19 May 2014 and last subject last visit 29 May 2015 for Part B. One clinical trial site at Aarhus University Hospital, Denmark

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
7 patients were screened and 6 patients were enrolled in Part A. 24 patients were screened and 20 patients were enrolled in Part B.

Reporting Groups

	Description
Part A	Pre-treatment phase of 2-4 weeks (Visit 1- Visit 2a) followed by viral reactivation phase of 3 weeks (Visit 2 to Visit 7) consisting of one cycle of romidepsin infusions at a dosing of 5 mg/m2 on days 0, 7, and 14. Post-activation phase of ~9 weeks (Visit 8 to Visit 11) to assess the effect of romidepsin on the size of latent HIV-1 reservoir.
Part B	Pre-treatment phase of 2-4 weeks (Visit 1-Visit 2) followed by a therapeutic HIV-1 immunization phase of 12 weeks (Visit 2 to Visit 7) in which 1.2 mg Vacc-4x was administered together with 0.06 mg rhuGM-CSF at Visits 2, 3, 4, 5, 6 and 7 follow by a follow-up period of 2 weeks (Visit 8). A viral reactivation phase of 3 weeks (Visit 9-Visit 11) consisting of one cycle of 3 romidepsin infusions (5 mg/m2) followed by a post-treatment observation phase of ~9 weeks (Visit 12-Visit 13) to assess the effect of the investigational treatment on the size of the latent HIV-1 reservoir. A monitored antiretroviral pause of up to 16 weeks (Visit 14-Visit 33).

Participant Flow:   Overall Study

	Part A	Part B
STARTED	6	20
COMPLETED	6	16
NOT COMPLETED	0	4
Withdrawal by Subject	0	3
Adverse Event	0	1

  Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
Part A	Pre-treatment phase of 2-4 weeks (Visit 1- Visit 2a) followed by viral reactivation phase of 3 weeks (Visit 2 to Visit 7) consisting of one cycle of romidepsin infusions at a dosing of 5 mg/m2 on days 0, 7, and 14. Post-activation phase of ~9 weeks (Visit 8 to Visit 11) to assess the effect of romidepsin on the size of latent HIV-1 reservoir.
Part B	Pre-treatment phase of 2-4 weeks (Visit 1-Visit 2) followed by a therapeutic HIV-1 immunization phase of 12 weeks (Visit 2 to Visit 7) in which 1.2 mg Vacc-4x was administered together with 0.06 mg rhuGM-CSF at Visits 2, 3, 4, 5, 6 and 7 follow by a follow-up period of 2 weeks (Visit 8). A viral reactivation phase of 3 weeks (Visit 9-Visit 11) consisting of one cycle of 3 romidepsin infusions (5 mg/m2) followed by a post-treatment observation phase of ~9 weeks (Visit 12-Visit 13) to assess the effect of the investigational treatment on the size of the latent HIV-1 reservoir. A monitored antiretroviral pause of up to 16 weeks (Visit 14-Visit 33).
Total	Total of all reporting groups

Baseline Measures

	Part A	Part B	Total
Overall Participants Analyzed; [Units: Participants]	6	20	26
Age, Customized; [Units: Participants]
>18 years
Participants Analyzed	6	20	26
>18 years	6	20	26
Gender; [Units: Participants]; Count of Participants
Participants Analyzed	6	20	26
Female	1 16.7%	3 15.0%	4 15.4%
Male	5 83.3%	17 85.0%	22 84.6%
Race (NIH/OMB); [Units: Participants]; Count of Participants
Participants Analyzed	6	20	26
American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
Asian	0 0.0%	1 5.0%	1 3.8%
Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
Black or African American	0 0.0%	1 5.0%	1 3.8%
White	6 100.0%	17 85.0%	23 88.5%
More than one race	0 0.0%	0 0.0%	0 0.0%
Unknown or Not Reported	0 0.0%	1 5.0%	1 3.8%
Region of Enrollment; [Units: Participants]
Denmark
Participants Analyzed	6	20	26
Denmark	6	20	26
Time since HIV diagnosis; [Units: Years]; Median (Full Range)
Participants Analyzed	6	20	26
	13.3; (7.0 to 22.6)	9.6; (2.6 to 28.7)	9.85; (2.6 to 28.7)
Time since HIV infection [1]; [Units: Years]; Median (Full Range)
Participants Analyzed	4	19	23
	13.5; (10.7 to 23.1)	10.2; (2.7 to 31.7)	12.2; (2.7 to 31.7)
[1] Information was not available for 2 patients in Part A and for 1 patient in Part B.
Time since ART initiation; [Units: Years]; Median (Full Range)
Participants Analyzed	6	20	26
	10.05; (4.2 to 14.5)	6.3; (2.4 to 18.1)	6.9; (2.4 to 18.1)
Latest pre-ART viral load [1]; [Units: copies/mL]; Median (Full Range)
Participants Analyzed	6	18	24
	123300; (1977 to 2450000)	67024; (3674 to 10000000)	72597.5; (1977 to 10000000)
[1] Pre-ART viral load was not availabel for 2 patrients in Part B.
Nadir CD4+ T-cell count; [Units: 10^6 cells/L]; Median (Full Range)
Participants Analyzed	6	20	26
	246.5; (40 to 340)	280; (60 to 710)	267.5; (40 to 710)
Mean CD4+ T-cell counts; [Units: 10^6 cells/L]; Median (Full Range)
Participants Analyzed	6	20	26
	807.5; (570 to 1015)	669.8; (465 to 1645)	712.3; (465 to 1645)

  Outcome Measures

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1. Primary:

Part A: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: 3 weeks ]

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2. Primary:

Part B: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. [ Time Frame: Day 161/175 ]

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3. Secondary:

Part A: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. Estimates of Change From Baseline of the Size of the Latent HIV-1 Reservoir in CD4+ Cells. [ Time Frame: Day 56/84 ]

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4. Secondary:

Part B: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: 287 days ]

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5. Secondary:

Part B: Level of HIV-1 Transcription. [ Time Frame: Day 105, 112 and 119 ]

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  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information

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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.

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: The Sponsor (or designee) will prepare a final report on the study. The Investigator may not publish or present any information on this study without the express written approval of the Sponsor. Additionally, the Sponsor, may, for any reason, withhold approval for publication or presentation.

Results Point of Contact:  

Name/Title: Maja Sommerfelt
Organization: Bionor Pharma ASA
phone: +4723010960
e-mail: ms@bionorpharma.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Leth S, Schleimann MH, Nissen SK, Højen JF, Olesen R, Graversen ME, Jørgensen S, Kjær AS, Denton PW, Mørk A, Sommerfelt MA, Krogsgaard K, Østergaard L, Rasmussen TA, Tolstrup M, Søgaard OS. Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV. 2016 Oct;3(10):e463-72. doi: 10.1016/S2352-3018(16)30055-8. Epub 2016 Jul 7.

Søgaard OS, Graversen ME, Leth S, Olesen R, Brinkmann CR, Nissen SK, Kjaer AS, Schleimann MH, Denton PW, Hey-Cunningham WJ, Koelsch KK, Pantaleo G, Krogsgaard K, Sommerfelt M, Fromentin R, Chomont N, Rasmussen TA, Østergaard L, Tolstrup M. The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. PLoS Pathog. 2015 Sep 17;11(9):e1005142. doi: 10.1371/journal.ppat.1005142. eCollection 2015 Sep.

Responsible Party:	Bionor Immuno AS
ClinicalTrials.gov Identifier:	NCT02092116 History of Changes
Other Study ID Numbers:	BPC01-001; 2013-004747-23 ( EudraCT Number )
First Submitted:	March 3, 2014
First Posted:	March 19, 2014
Results First Submitted:	November 8, 2016
Results First Posted:	March 1, 2017
Last Update Posted:	March 1, 2017