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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT01933594

Collaborator

(none)

Enrollment

Locations

Arms

47.4

Actual Duration (Months)

5.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Antiretroviral therapy (ART) can reduce HIV to very low levels in the blood, but it cannot cure HIV infection because a small amount of virus remains in cells as a hidden (latent) form. The purpose of this study was to evaluate the safety and efficacy of single dose and multiple dose administration of romidepsin (RMD) in HIV-infected adults.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Romidepsin Drug: Placebo for Romidepsin	Phase 1/Phase 2

Detailed Description

A major challenge in eradicating HIV-1 infection is the persistence of virus in long-lived cells, such as latently infected memory CD4 T cells. One approach for eliminating the HIV-1 reservoir is to activate viral replication in these latently infected CD4 T cells by targeting cellular mechanisms that repress proviral transcription. Histone deacetylase inhibitors (HDACis), such as RMD, induce HIV-1 expression by increasing acetylation and facilitating transcriptional activation of HIV-1. RMD administered in combination with ART may serve as an important component of a strategy to eradicate the HIV-1 latent reservoir. The purpose of this study was to evaluate the safety and efficacy of single dose and multiple dose administration of RMD in HIV-infected adults.

Participants were sequentially enrolled into four cohorts and randomly assigned to receive either RMD or placebo. The cohorts differed in the dose of RMD given. Participants in Cohorts 1, 2, and 3 had one intravenous (IV) infusion of RMD or placebo at Day 0. Participants in Cohort 4 had four IV infusions of RMD or placebo at Days 0, 14, 28, and 42.

For participants in Cohorts 1, 2, and 3, study duration was 4 weeks. For participants in Cohort 4, study duration was a minimum of 24 weeks and a maximum of 48 weeks.

Participants attended several study visits, which could include a physical examination, blood and urine collection, pharmacokinetic (PK) sampling, and an electrocardiogram (ECG).

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Study of Romidepsin in HIV-Infected Adults With Suppressed Viremia on Antiretroviral Therapy to Assess Safety, Tolerability, and Activation of HIV-1 Expression

Actual Study Start Date :

May 5, 2014

Actual Primary Completion Date :

Apr 16, 2018

Actual Study Completion Date :

Apr 16, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1-Arm 1A (Romidepsin) Participants in Cohort 1, Arm 1A received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of Romidepsin was 0.5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight).	Drug: Romidepsin RMD administered over 4 hours via an intravenous (IV) catheter. Other Names: RMD Istodax
Placebo Comparator: Cohort 1-Arm 1B (Placebo for Romidepsin) Participants in Cohort 1, Arm 1B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of sodium chloride for injection placebo was 0.5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight).	Drug: Placebo for Romidepsin Placebo for RMD administered over 4 hours via an IV catheter. Other Names: 0.9% NaCl 0.9% sodium chloride
Experimental: Cohort 2-Arm 2A (Romidepsin) Participants in Cohort 2, Arm 2A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of Romidepsin was 2 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight).	Drug: Romidepsin RMD administered over 4 hours via an intravenous (IV) catheter. Other Names: RMD Istodax
Placebo Comparator: Cohort 2-Arm 2B (Placebo for Romidepsin) Participants in Cohort 2, Arm 2B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of sodium chloride for injection placebo was 2 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight).	Drug: Placebo for Romidepsin Placebo for RMD administered over 4 hours via an IV catheter. Other Names: 0.9% NaCl 0.9% sodium chloride
Experimental: Cohort 3-Arm 3A (Romidepsin) Participants in Cohort 3, Arm 3A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of Romidepsin was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight).	Drug: Romidepsin RMD administered over 4 hours via an intravenous (IV) catheter. Other Names: RMD Istodax
Placebo Comparator: Cohort 3-Arm 3B (Placebo for Romidepsin) Participants in Cohort 3, Arm 3B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of sodium chloride for injection placebo was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight).	Drug: Placebo for Romidepsin Placebo for RMD administered over 4 hours via an IV catheter. Other Names: 0.9% NaCl 0.9% sodium chloride
Experimental: Cohort 4-Arm 4A (Romidepsin) 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. Dose of Romidepsin was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight).	Drug: Romidepsin RMD administered over 4 hours via an intravenous (IV) catheter. Other Names: RMD Istodax
Placebo Comparator: Cohort 4-Arm 4B (Placebo for Romidepsin) 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. Dose of sodium chloride for injection placebo was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight).	Drug: Placebo for Romidepsin Placebo for RMD administered over 4 hours via an IV catheter. Other Names: 0.9% NaCl 0.9% sodium chloride

Outcome Measures

Primary Outcome Measures

Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohorts 1-3 Romidepsin Arms [Measured from the time of Romidepsin administration (at entry) until 28 days after the administration]
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.
Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohort 4 Romidepsin Arm [Measured from the time of the first Romidepsin administration through 28 days after the last administration (at day 42)]
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.
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3 [Pre-entry, entry, 24 and 48 hours after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4 [Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)]
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.
Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T-cells in Cohorts 1-3 [Pre-entry and 24 hours after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4 [Pre-entry, entry and 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)]
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.

Secondary Outcome Measures

Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3 [Pre-entry, entry, 6 hours, 12 hours, 7 days, 14 days and 28 days after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4 [Pre-entry, entry and 72 hours after the second administration of Romidepsin or placebo (at day 14)]
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.
Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T Cells in Cohorts 1-3 [Pre-entry and 14 days after the administration of RMD or placebo (at entry)]
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.
Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4 [Pre-entry and 72 hours after the second administration of Romidepsin or placebo (at day 14)]
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.
Change From Baseline in Histone Acetylation (Median FITC Ac-Histone) in CD3+ Cells in Cohorts 1-3 [Hour 0 and 24 hours after the single administration of RMD or placebo (at entry)]
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.
Change From Baseline in Histone Acetylation in (Median FITC Ac-histone) in CD3+ Cells in Cohort 4 [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)]
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.
Change From Baseline in Total HIV-1 DNA in Resting or Total CD4 T Cells in Cohorts 1-3 [Pre-entry, 24 hours and 14 days after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Total HIV-1 DNA in PBMCs in Cohort 4 [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)]
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.
PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Efavirenz, Dolutegravir, or Raltegravir) in Cohorts 1-3 [At hours 0, 4, 6, 12 and 24]
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.
PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Dolutegravir or Raltegravi) in Cohort 4 [Pre, post and 24 hours after the third and fourth administrations of Romidepsin or placebo (at days 28 and 42)]
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.
HIV-1 RNA Levels in Cohorts 1-3 [7 days after the administration of Romidepsin or placebo (at entry)]
HIV-1 RNA levels at 7 days after the single administration of Romidepsin or placebo (at entry)
HIV-1 RNA Levels in Cohort 4 [7 days after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)]
HIV-1 RNA levels at 7 days after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Number of Participants With Reported Grade 2-4 AEs in Cohorts 1-3 [Measured from study entry to off study]
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.
Number of Participants With Reported Grade 2-4 AEs in Cohort 4 [Measured from study entry to off study]
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.
Change From Baseline in CD4+ and CD8+ T Cell Percent in Cohorts 1-3 [Measured through participant's last study visit]
Change in CD4+ and CD8+T cell percent from baseline to after the single administration of Romidepsin or placebo
Change From Baseline in CD4+ T Cell Percent in Cohort 4 [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)]
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
Change From Baseline in CD8+ T Cell Percent in Cohort 4 [Measured through 28 days after the single administration of RMD or placebo (at entry, and days 14, 28 and 42)]
Change in CD8+ T cell percent from baseline to after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohorts 1-3 [Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohorts 1-3 [Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohorts 1-3 [Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohorts 1-3 [Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohort 4 [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)]
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.
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohort 4 [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)]
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.
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohort 4 [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)]
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.
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohort 4 [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]
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.
Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3 [Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3 [Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4 [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)]
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.
Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4 [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)]
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.
Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD4+ T-cells in Cohorts 1-3 [Hour 0 and 24 hours after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD8+ T-cells in Cohorts 1-3 [Hour 0 and 24 hours after the single administration of Romidepsin or placebo (at entry)]
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.
Change From Baseline in PTEF-b Phosphorylation (pNFKB+%) in CD4+ T-cells in Cohort 4 [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)]
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.
Change From Baseline in PTEF-b Phosphorylation (pS175+%) in CD4+ T-cells in Cohort 4 [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)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria: Cohorts 1, 2, & 3

HIV-1 infection, documented by any licensed rapid HIV test or HIV E/CIA test kit at any time prior to study entry & confirmed by a licensed Western blot or a 2nd antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA
Receiving 2 (or more) nucleoside or nucleotide reverse transcriptase inhibitors with raltegravir, dolutegravir, or efavirenz for at least 90 days prior to study entry with no intention to change for the duration of the study
Documentation of at least 2 historical HIV-1 RNA measurements <50 copies/mL while on ART obtained by standard ultrasensitive assay. Documentation of the 1st measurement must be from a result obtained between 365-91 days, inclusive, prior to study entry. Documentation of the 2nd measurement must be from a result obtained between 730-366 days, inclusive, prior to study entry. In addition, there must be no HIV-1 RNA values ≥50 copies/mL for at least 365 days prior to study entry.
CD4 cell count ≥300 cells/mm^3 obtained within 90-50 days prior to study entry at any US laboratory that has a CLIA certification or equivalent
HIV-1 RNA level of <50 copies/mL obtained by standard ultrasensitive assay within 90-50 days prior to study entry
HIV-1 RNA level of ≥0.4 copies/mL obtained by SCA within 90-50 days prior to study entry. This result must be available prior to the pre-entry visit
The following laboratory values obtained within 21-0 days prior to study entry by any laboratory that has a CLIA certification or equivalent
ANC ≥1500 cells/mm^3
Hemoglobin ≥12.0 g/dL for men & >11.0 g/dL for women
Platelet count ≥120,000/mm^3
The following laboratory values obtained within 21-7 days prior to study entry by any laboratory that has a CLIA certification or equivalent
CrCl ≥60 mL/min
Potassium & magnesium within normal limits
AST (SGOT) <2.0 x ULN
ALT (SGPT) <2.0 x ULN
Alkaline phosphatase <2.0 x ULN
Total bilirubin <2.5 x ULN
HCV antibody negative result within 90-50 days prior to study entry or, for study candidates who are HCV antibody positive (based on testing performed at any time prior to study entry), a negative HCV RNA result obtained within 90-50 days prior to study entry
Negative HBsAg result obtained within 90-50 days prior to study entry or a positive HBsAb result at any time prior to study entry
For females of reproductive potential, negative serum or urine pregnancy test (latter with sensitivity of ≤25 mIU/mL) at the screening visit, pre-entry visit within 21-7 days prior to study entry, & at entry prior to romidepsin infusion, by any US laboratory that has a CLIA certification or equivalent
Female candidates of reproductive potential must refrain from participating in active attempts to become pregnant, &, if participating in sexual activity that could lead to pregnancy, must agree to use at least 2 reliable forms of contraception that are non-estrogen based. All female participants of reproductive potential must be instructed to use contraceptives for 6 months/180 days after completing RMD or placebo infusion
Karnofsky performance score ≥80 within 21-7 days prior to study entry
Men and women age ≥ 18 years
Ability & willingness to provide written informed consent
Investigator anticipates that a fully active alternative ART regimen could be constructed in the event of virologic failure on the current ART regimen

Exclusion Criteria: Cohorts 1, 2, & 3

History of or current malignancy requiring cytotoxic therapy
Bacterial, fungal, or viral infection (other than HIV) requiring systemic therapy within 30 days prior to entry
History of or current CMV end organ disease (eg, retinitis)
History of or current AIDS-related syndromes or symptoms that pose a perceived excessive risk for study drug-related morbidity, as determined by the investigator
Chronic, acute, or recurrent infections that are current & serious in the opinion of the investigator & for which the participant has not completed at least 14 consecutive days of therapy within 30 days prior to study entry and/or is not clinically stable
Active autoimmune disorders including but not limited to: inflammatory bowel diseases, scleroderma, severe psoriasis as determined by the investigator, systemic lupus erythematosus, rheumatoid arthritis & optic neuritis
History of seizure disorders
History of anticonvulsant use within 60 days prior to study entry
History of MI within 6 months prior to study entry, history of QTc prolongation (defined as ECG with QTc intervals >450 ms) at any time prior to study entry, NYHA class III or IV heart failure at any time prior to study entry, or family history of prolonged QTc syndrome
Breastfeeding
Use of immunomodulators (eg, interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry
Any vaccination within 30 days prior to entry or intent to receive an elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study
Intent to use cytokines (e.g., IL-2 or IL-12) during the course of the study. Prior administration of cytokines is not an exclusion criterion; however, at least 60 days between the most recent cycle of any cytokine and study entry is required
Within 60 days prior to study entry, use of systemic azole antifungals (voriconazole, itraconazole, ketoconazole); dexamethasone; macrolide antibiotics (azithromycin, clarithromycin, erythromycin); ARVs that are inhibitors of, or are metabolized by, CYP3A4 (atazanavir, ritonavir, nelfinavir, indinavir, saquinavir, darunavir, lopinavir, rilpivirine, maraviroc); cobicistat; warfarin; nefazodone; rifamycins (rifabutin, rifampin, rifapentine); St. John's Wort; carbamazepine; phenytoin; phenobarbital; amiodarone; dofetilide; pimozide; procainamide; quinidine; sotalol; & birth control products containing estrogen; drugs that are p-glycoprotein inhibitors; & drugs that prolong the QTc interval with a risk of Torsades de Pointes
Known allergy, sensitivity, or any hypersensitivity to components of RMD or its formulation
Use of histone deacetylase inhibitors (eg, vorinostat, valproic acid) at any time prior to study entry
Active illicit drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
Acute or serious illness requiring systemic treatment and/or hospitalization that is not resolved within 30 days prior to entry
Psychosocial conditions that would prevent study compliance and follow-up, as determined by the investigator
Documented opportunistic infections within 60 days prior to entry

Inclusion Criteria: Cohort 4, Step 1

HIV-1 infection, documented by any licensed rapid HIV test or HIV E/CIA test kit at any time prior to study entry & confirmed by a licensed Western blot or a 2nd antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA
Receiving 2 or more nucleoside or nucleotide reverse transcriptase inhibitors with raltegravir or dolutegravir for at least 90 days prior to study entry with no intention to change for the duration of the study
Documentation of at least 2 historical HIV-1 RNA measurements <50 copies/mL while on ART obtained by standard ultrasensitive assay. Documentation of the first measurement must be from a result obtained between 365-61 days, inclusive, prior to study entry. Documentation of the second measurement must be from a result obtained between 730-366 days, inclusive, prior to study entry. In addition, there must be no HIV-1 RNA values ≥50 copies/mL for at least 365 days prior to study entry
CD4 cell count ≥300 cells/mm^3 obtained between 36-60 days prior to study entry (screening visit) at any US laboratory that has a CLIA certification or equivalent
HIV-1 RNA level of <50 copies/mL obtained by standard ultrasensitive assay at screening (between 36-60 days prior to study entry)
The following laboratory values obtained at pre-entry (between 3-14 days prior to study entry) by any laboratory that has a CLIA certification or equivalent
ANC ≥1500 cells/mm^3
Hemoglobin ≥12.0 g/dL for men & >11.0 g/dL for women
Platelet count ≥120,000/mm^3
CrCl ≥60 mL/min
Potassium & magnesium within normal limits
AST (SGOT) <2.0 x ULN
ALT (SGPT) <2.0 x ULN
Alkaline phosphatase <2.0 x ULN
Total bilirubin <2.5 x ULN
HCV antibody negative result at screening (between 36-60 days prior to study entry) or, for study candidates who are HCV antibody positive (based on testing performed at any time prior to study entry), a negative HCV RNA result obtained at screening
Negative HBsAg result obtained at screening (between 36-60 days prior to study entry) or a positive HBsAb result at any time prior to study entry
For females of reproductive potential, negative urine pregnancy test (with a sensitivity of ≤25 mIU/mL) at screening (between 36-60 days prior to study entry), at pre-entry (between 3-14 days prior to study entry), & at entry prior to infusion, by any US laboratory that has a CLIA certification or equivalent
Female candidates of reproductive potential must refrain from participating in active attempts to become pregnant, &, if participating in sexual activity that could lead to pregnancy, must agree to use at least 2 reliable forms of contraception that are non-estrogen based. All participants of reproductive potential will be instructed to use contraceptives for 6 months or 180 days after completing RMD/placebo infusion
Karnofsky performance score ≥80 at pre-entry (between 3-14 days prior to study entry)
Men and women age ≥ 18 years
Ability & willingness to provide written informed consent
Investigator anticipates that a fully active alternative ART regimen could be constructed in the event of virologic failure on the current ART regimen

Exclusion Criteria: Cohort 4, Step 1

History of or current malignancy requiring cytotoxic therapy
Bacterial, fungal or viral infection (other than HIV) requiring systemic therapy within 30 days prior to entry
History of or current CMV end organ disease (eg, retinitis)
History of or current AIDS-related syndromes or symptoms that pose a perceived excessive risk for study drug-related morbidity, as determined by the investigator
Chronic, acute, or recurrent infections that are current & serious, in the opinion of the investigator, for which the participant has not completed at least 14 consecutive days of therapy within 30 days prior to study entry and/or is not clinically stable
Active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis as determined by the investigator, systemic lupus erythematosus, rheumatoid arthritis, & optic neuritis
History of seizure disorders
History of anticonvulsant use within 60 days prior to study entry
History of MI within 6 months prior to study entry, history of QTc prolongation (defined as ECG with QTc intervals >450 ms) at any time prior to study entry, NYHA class III or IV heart failure at any time prior to study entry, or family history of prolonged QTc syndrome
Breastfeeding
Use of immunomodulators (eg, interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry
Any vaccination within 30 days prior to entry or intent to receive an elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study
Intent to use cytokines (eg, IL-2 or IL-12) during the course of the study
Within 60 days prior to study entry, use of systemic azole antifungals (voriconazole, itraconazole, ketoconazole), dexamethasone, macrolide antibiotics (azithromycin, clarithromycin, erythromycin), antiretrovirals that are inhibitors of, or are metabolized by CYP3A4 (atazanavir, ritonavir, nelfinavir, indinavir, saquinavir, darunavir, lopinavir, rilpivirine, maraviroc), cobicistat, warfarin, nefazodone, rifamycins (rifabutin, rifampin, rifapentine), St. John's Wort, carbamazepine, phenytoin, phenobarbital, amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, & birth control products containing estrogen, drugs that are p-glycoprotein inhibitors, & drugs that prolong the QTc interval with a risk of Torsades de Pointes
Known allergy/sensitivity or any hypersensitivity to components of RMD or its formulation
Use of histone deacetylase inhibitors (eg, vorinostat, valproic acid) at any time prior to study entry
Active illicit drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
Acute or serious illness requiring systemic treatment and/or hospitalization that is not resolved within 30 days prior to entry
Psychosocial conditions that would prevent study compliance & follow-up as determined by the investigator
Documented opportunistic infections within 60 days prior to entry
Use of any of the medications listed in the Prohibited Medications table in the protocol

See the protocol for Inclusion and Exclusion Criteria for Cohort 4, Steps 2, 3, and 4.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama CRS	Birmingham	Alabama	United States	35294
2	UCLA CARE Center CRS	Los Angeles	California	United States	90035
3	University of Colorado Hospital CRS	Aurora	Colorado	United States	80045
4	Massachusetts General Hospital CRS (MGH CRS)	Boston	Massachusetts	United States	02114
5	University of Rochester Adult HIV Therapeutic Strategies Network CRS	Rochester	New York	United States	14642
6	Chapel Hill CRS	Chapel Hill	North Carolina	United States	27599
7	Ohio State University CRS	Columbus	Ohio	United States	43210
8	Penn Therapeutics, CRS	Philadelphia	Pennsylvania	United States	19104
9	University of Pittsburgh CRS	Pittsburgh	Pennsylvania	United States	15213
10	University of Washington AIDS CRS	Seattle	Washington	United States	98104-9929

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair: John Mellors, MD, University of Pittsburgh
Study Chair: Deborah McMahon, MD, University of Pittsburgh

Study Documents (Full-Text)

More Information

Additional Information:

DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014. Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Publications

Responsible Party:

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT01933594

Other Study ID Numbers:

A5315
11892
ACTG 5315

First Posted:

Sep 2, 2013

Last Update Posted:

Nov 1, 2021

Last Verified:

Oct 1, 2021

Additional relevant MeSH terms:

HIV Infections

Romidepsin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

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)
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

Baseline Characteristics

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
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 Participants	12	12	12	7	13	3	59
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	12 100%	11 91.7%	6 85.7%	11 84.6%	3 100%	55 93.2%
>=65 years	0 0%	0 0%	1 8.3%	1 14.3%	2 15.4%	0 0%	4 6.8%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	50	52	51	51	56	45	52
Sex: Female, Male (Count of Participants)
Female	1 8.3%	1 8.3%	1 8.3%	0 0%	4 30.8%	1 33.3%	8 13.6%
Male	11 91.7%	11 91.7%	11 91.7%	7 100%	9 69.2%	2 66.7%	51 86.4%
Race/Ethnicity, Customized (Count of Participants)
White non-Hispanic	8 66.7%	8 66.7%	6 50%	5 71.4%	6 46.2%	2 66.7%	35 59.3%
Black non-Hispanic	4 33.3%	3 25%	5 41.7%	2 28.6%	6 46.2%	1 33.3%	21 35.6%
Hispanic (regardless of race)	0 0%	0 0%	1 8.3%	0 0%	1 7.7%	0 0%	2 3.4%
Asian, Pacific Islander	0 0%	1 8.3%	0 0%	0 0%	0 0%	0 0%	1 1.7%
Region of Enrollment (Count of Participants)
United States	12 100%	12 100%	12 100%	7 100%	13 100%	3 100%	59 100%
Baseline SCA in Cohorts 1-3 (log10 copies/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log10 copies/mL]	0.08	-0.2	0.22	0.38	NA
Baseline SCA in Cohort 4 (log10 copies/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log10 copies/mL]	-0.2	-0.25	NA
Baseline CA RNA in Cohorts 1-3 (log10 copies/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log10 copies/mL]	1.9	2.6	2.3	2.8	NA
Baseline CA RNA in Cohort 4 (log10 copies/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log10 copies/mL]	1.19	1.61	NA

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohorts 1-3 Romidepsin Arms
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

Outcome Measure Data

Analysis Population Description
Participants in Cohorts 1-3 who received Romidepsin

Arm/Group Title	Cohorts 1-3 (Romidepsin)
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.
Measure Participants	36
Number (95% Confidence Interval) [proportion of participants]	0 0%

2. Primary Outcome

Title	Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohort 4 Romidepsin Arm
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)

Outcome Measure Data

Analysis Population Description
Participants in Cohort 4 who received Romidepsin

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)
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.
Measure Participants	13
Number (95% Confidence Interval) [proportion of participants]	0.077 0.6%

3. Primary Outcome

Title	Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Median (Inter-Quartile Range) [log10 copies/mL]	0.12	0.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Primary Outcome

Title	Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	0	-0.11
Change from baseline to 24 hours post infusion 2	0.03	0.15
Change from baseline to 24 hours post infusion 3	0.3	0.47
Change from baseline to 24 hours post infusion 4	0	0.33

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

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 3
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Primary Outcome

Title	Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T-cells in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Median (Inter-Quartile Range) [log10 (copies/10^6 resting CD4 cells)]	-.009	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Primary Outcome

Title	Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	-0.06	-0.16
Change from baseline to 24 hours post infusion 2	-0.07	-0.52
Change from baseline to 24 hours post infusion 3	-0.44	-0.02
Change from baseline to 24 hours post infusion 4	-0.05	-0.3

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

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 3
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change from baseline to 6 hours post infusion	-0.02	0.14
Change from baseline to 12 hours post infusion	0	0.27
Change from baseline to 7 days post infusion	0	0.27
Change from baseline to 14 days post infusion	0	-0.13
Change from baseline to 28 days post infusion	0	-0.08

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

Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	12	3
Median (Inter-Quartile Range) [log10 copies/mL]	0	0.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T Cells in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	34	7
Median (Inter-Quartile Range) [log10 copies/mL]	0.02	-0.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	12	3
Median (Inter-Quartile Range) [log10 copies/mL]	-0.26	-0.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

11. Secondary Outcome

Title	Change From Baseline in Histone Acetylation (Median FITC Ac-Histone) in CD3+ Cells in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	32	6
Median (Inter-Quartile Range) [arbitrary units]	-7	-194

12. Secondary Outcome

Title	Change From Baseline in Histone Acetylation in (Median FITC Ac-histone) in CD3+ Cells in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	2402	749
Change from baseline to 24 hours post infusion 2	2774	8497
Change from baseline to 72 hours post infusion 2	4741	4741
Change from baseline to 24 hours post infusion 3	4522	5665
Change from baseline to 24 hours post infusion 4	4342	2697

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 72 hours post infusion 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

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 3
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Change From Baseline in Total HIV-1 DNA in Resting or Total CD4 T Cells in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change from baseline to 24 hours post infusion	-0.04	0.05
Change from baseline to 14 days post infusion	-0.01	-0.05

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

Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

Title	Change From Baseline in Total HIV-1 DNA in PBMCs in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	-0.06	-0.04
Change from baseline to 24 hours post infusion 2	-0.13	-0.11
Change from baseline to 72 hours post infusion 2	-0.13	-0.07
Change from baseline to 24 hours post infusion 3	-0.06	-0.13
Change from baseline to 24 hours post infusion 4	-0.14	-0.07

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 72 hours post infusion 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

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 3
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

15. Secondary Outcome

Title	PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Efavirenz, Dolutegravir, or Raltegravir) in Cohorts 1-3
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

Outcome Measure Data

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)
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.
Measure Participants	12	12	12	7
RMD PK concentration at Hour 0	NA	NA	NA
RMD PK concentration at Hour 4	12	75.2	89
RMD PK concentration at Hour 6	3.2	2.7	2.6
RMD PK concentration at Hour 12	NA	NA	NA
RMD PK concentration at Hour 24	NA	NA	NA
EFV PK concentration at Hour 0	2030	2560	2612	2520
EFV PK concentration at Hour 24	2105	1870	2886	1600
RAL PK concentration at Hour 0	777	910	401
RAL PK concentration at Hour 24	1234	398	142
DTG PK concentration at Hour 0	4035	2988
DTG PK concentration at Hour 24	2190	2399

16. Secondary Outcome

Title	PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Dolutegravir or Raltegravi) in Cohort 4
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)

Outcome Measure Data

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)
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.
Measure Participants	13	3
RMD PK concentration pre infusion 3	207
RMD PK concentration post infusion 3	69
RMD PK concentration pre infusion 4	NA
RMD PK concentration post infusion 4	134
RAL PK concentration 24 hours post infusion 3	906
RAL PK concentration 24 hours post infusion 4	567
DTG PK concentration 24 hours post infusion 3	2124	913
DTG PK concentration 24 hours post infusion 4	1568	833

17. Secondary Outcome

Title	HIV-1 RNA Levels in Cohorts 1-3
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)

Outcome Measure Data

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)
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.
Measure Participants	12	12	12	7
< 40 copies/mL	11 91.7%	12 100%	12 100%	7 100%
40-199 copies/mL	1 8.3%	0 0%	0 0%	0 0%

18. Secondary Outcome

Title	HIV-1 RNA Levels in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
< 40 copies/mL	13 108.3%	2 16.7%
40 - 199 copies/mL	0 0%	0 0%
< 40 copies/mL	8 66.7%	3 25%
40 - 199 copies/mL	0 0%	0 0%
< 40 copies/mL	11 91.7%	3 25%
40 - 199 copies/mL	0 0%	0 0%
< 40 copies/mL	11 91.7%	3 25%
40 - 199 copies/mL	0 0%	0 0%

19. Secondary Outcome

Title	Number of Participants With Reported Grade 2-4 AEs in Cohorts 1-3
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

Outcome Measure Data

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)
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.
Measure Participants	12	12	12	7
Count of Participants [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
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

Outcome Measure Data

Analysis Population Description
Cohort 4 participants

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Count of Participants [Participants]	5 41.7%	0 0%

21. Secondary Outcome

Title	Change From Baseline in CD4+ and CD8+ T Cell Percent in Cohorts 1-3
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

Outcome Measure Data

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)
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.
Measure Participants	0	0

22. Secondary Outcome

Title	Change From Baseline in CD4+ T Cell Percent in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	-2.5	-2
Change from baseline to 24 hours post infusion 2	-4.5	0.5
Change from baseline to 24 hours post infusion 3	-3.5	1
Change from baseline to 24 hours post infusion 4	-4.5	0.5
Change from baseline to 2 weeks post infusion 4	-0.5	-0.5
Change from baseline to 5 weeks post infusion 4	-1.8	0
Change from baseline to 10 weeks post infusion 4	-2.8	-0.5
Change from baseline to 18 weeks post infusion 4	-0.5	-2.5

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

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 3
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 2 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 5 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 10 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 18 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

23. Secondary Outcome

Title	Change From Baseline in CD8+ T Cell Percent in Cohort 4
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)

Outcome Measure Data

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)
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.
Measure Participants	0	0

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
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change from baseline to 48 hours post infusion	0.5	0.4
Change from baseline to 7 days post infusion	1	-1
Change from baseline to 28 days post infusion	1.2	-1.4

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

Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change from baseline to 48 hours post infusion	0.1	0.3
Change from baseline to 7 days post infusion	0.8	-1.3
Change from baseline to 28 days post infusion	0.3	-0.1

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

Statistical Test of Hypothesis	p-Value	0.89
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

26. Secondary Outcome

Title	Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change from baseline to 48 hours post infusion	0	0
Change from baseline to 7 days post infusion	0	0
Change from baseline to 28 days post infusion	0	0

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

Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

27. Secondary Outcome

Title	Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change from baseline to 48 hours post infusion	0	0
Change from baseline to 7 days post infusion	0	0
Change from baseline to 28 days post infusion	0	0

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

Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

28. Secondary Outcome

Title	Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	0.2	0.5
Change from baseline to 24 hours post infusion 4	1	2
Change from baseline to 10 weeks post infusion 4	0.4	0.7

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 10 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

29. Secondary Outcome

Title	Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	0.6	0.2
Change from baseline to 24 hours post infusion 4	1.1	1.1
Change from baseline to 10 weeks post infusion 4	-0.3	2.8

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	hange from baseline to 24 hours post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 10 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.028
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

30. Secondary Outcome

Title	Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	0	-0.1
Change from baseline to 24 hours post infusion 4	0	-0.1
Change from baseline to 10 weeks post infusion 4	0	-0.1

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 10 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

31. Secondary Outcome

Title	Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohort 4
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

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	0	0
Change from baseline to 24 hours post infusion 4	0	-0.1
Change from baseline to 10 weeks post infusion 4	0	0

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 10 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.81
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change from baseline to 48 hours post infusion	0.2	1.2
Change from baseline to 7 days post infusion	0.6	0
Change from baseline to 28 days post infusion	1.2	-1.3

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

Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change from baseline to 48 hours post infusion	-0.1	1.8
Change from baseline to 7 days post infusion	0.3	-1.1
Change from baseline to 28 days post infusion	0.9	-1.9

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

Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	0.5	-1.4
Change from baseline to 24 hours post infusion 4	-2	0.9
Change from baseline to 10 weeks post infusion 4	0.3	0.1

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 10 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	0.1	-4.1
Change from baseline to 24 hours post infusion 4	-2.5	-.6
Change from baseline to 10 weeks post infusion 4	0.9	-0.8

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 10 weeks post infusion 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

36. Secondary Outcome

Title	Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD4+ T-cells in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change in pNFKB+% on CD4	20	19.3
Change in pS175% on CD4	18.1	6

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

Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

37. Secondary Outcome

Title	Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD8+ T-cells in Cohorts 1-3
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)

Outcome Measure Data

Analysis Population Description
Cohorts 1-3 participants with available data

Arm/Group Title	Cohorts 1-3 (Romidepsin)	Cohorts 1-3 (Placebo for Romidepsin)
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.
Measure Participants	36	7
Change in pNFKB+% on CD8	16.5	3.8
Change in pS175% on CD8	26.5	25.3

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

Statistical Test of Hypothesis	p-Value	0.81
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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

Statistical Test of Hypothesis	p-Value	0.81
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

38. Secondary Outcome

Title	Change From Baseline in PTEF-b Phosphorylation (pNFKB+%) in CD4+ T-cells in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	5.04	0.01
Change from baseline to 24 hours post infusion 2	8.78	0
Change from baseline to 72 hours post infusion 2	6.39	0
Change from baseline to 24 hours post infusion 3	5.78	0
Change from baseline to 24 hours post infusion 4	9.63	0

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 72 hours post infusion 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

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 3
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

39. Secondary Outcome

Title	Change From Baseline in PTEF-b Phosphorylation (pS175+%) in CD4+ T-cells in Cohort 4
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)

Outcome Measure Data

Analysis Population Description
Cohort 4 participants with available data

Arm/Group Title	Cohort 4-Arm 4A (Romidepsin)	Cohort 4-Arm 4B (Placebo for Romidepsin)
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.
Measure Participants	13	3
Change from baseline to 24 hours post infusion 1	9.93	-0.01
Change from baseline to 24 hours post infusion 2	17	-0.01
Change from baseline to 72 hours post infusion 2	11	-0.01
Change from baseline to 24 hours post infusion 3	14.85	0
Change from baseline to 24 hours post infusion 4	16.52	0.01

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 1
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

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 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohorts 1-3 (Romidepsin), Cohorts 1-3 (Placebo for Romidepsin)
	Comments	Change from baseline to 72 hours post infusion 2
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

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 3
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

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 4
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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)
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)
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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		1/3 (33.3%)
Infections and infestations
Abdominal wall abscess	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		1/3 (33.3%)
Other (Not Including 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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/12 (66.7%)		6/12 (50%)		1/12 (8.3%)		3/7 (42.9%)		9/13 (69.2%)		2/3 (66.7%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		1/3 (33.3%)
Cardiac disorders
Bradycardia	0/12 (0%)		0/12 (0%)		0/12 (0%)		1/7 (14.3%)		0/13 (0%)		0/3 (0%)
Ear and labyrinth disorders
Deafness	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Tinnitus	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Eye disorders
Eye discharge	0/12 (0%)		0/12 (0%)		0/12 (0%)		1/7 (14.3%)		0/13 (0%)		0/3 (0%)
Vision blurred	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Gastrointestinal disorders
Abdominal pain	1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		1/3 (33.3%)
Diarrhoea	1/12 (8.3%)		0/12 (0%)		0/12 (0%)		1/7 (14.3%)		0/13 (0%)		0/3 (0%)
Dysphagia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Nausea	1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		2/13 (15.4%)		0/3 (0%)
Vomiting	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
General disorders
Fatigue	3/12 (25%)		1/12 (8.3%)		0/12 (0%)		1/7 (14.3%)		1/13 (7.7%)		0/3 (0%)
Malaise	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		1/3 (33.3%)
Pyrexia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		2/3 (66.7%)
Infections and infestations
Abscess bacterial	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		1/3 (33.3%)
Acute sinusitis	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		1/7 (14.3%)		0/13 (0%)		0/3 (0%)
Bacterial vaginosis	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Escherichia urinary tract infection	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Influenza	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		1/3 (33.3%)
Onychomycosis	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Upper respiratory tract infection	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Viral tonsillitis	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Injury, poisoning and procedural complications
Contusion	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Infusion related reaction	1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Ligament sprain	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Meniscus injury	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Skin abrasion	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Investigations
Blood creatinine increased	2/12 (16.7%)		0/12 (0%)		1/12 (8.3%)		0/7 (0%)		3/13 (23.1%)		0/3 (0%)
Blood glucose increased	1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Blood pressure increased	0/12 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Creatinine renal clearance decreased	0/12 (0%)		0/12 (0%)		0/12 (0%)		1/7 (14.3%)		0/13 (0%)		0/3 (0%)
Electrocardiogram PR prolongation	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Electrocardiogram QT interval normal	1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Electrocardiogram QT prolonged	3/12 (25%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Haemoglobin abnormal	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Haemoglobin decreased	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		1/3 (33.3%)
Neutrophil count decreased	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Metabolism and nutrition disorders
Abnormal loss of weight	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Arthritis	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Bursitis	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Joint effusion	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Joint noise	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Joint swelling	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Mobility decreased	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Myalgia	1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Nervous system disorders
Dysgeusia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Headache	0/12 (0%)		2/12 (16.7%)		0/12 (0%)		1/7 (14.3%)		3/13 (23.1%)		0/3 (0%)
Presyncope	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Psychiatric disorders
Anxiety	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		2/13 (15.4%)		0/3 (0%)
Renal and urinary disorders
Chromaturia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Dysuria	1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Reproductive system and breast disorders
Pelvic pain	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		1/3 (33.3%)
Nasal congestion	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Oropharyngeal pain	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Rhinorrhoea	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Upper-airway cough syndrome	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Wheezing	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Erythema	1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Hyperhidrosis	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Nail discolouration	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		0/3 (0%)
Pruritus	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Swelling face	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)
Surgical and medical procedures
Abdominoplasty	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		0/13 (0%)		1/3 (33.3%)
Vascular disorders
Hypotension	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/7 (0%)		1/13 (7.7%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.

Results Point of Contact

Name/Title	ACTG Clinicaltrials.gov Coordinator
Organization	ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone	(301) 628-3313
Email	ACTGCT.Gov@s-3.com

Responsible Party:

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT01933594

Other Study ID Numbers:

A5315
11892
ACTG 5315

First Posted:

Sep 2, 2013

Last Update Posted:

Nov 1, 2021

Last Verified:

Oct 1, 2021