Phase 2
Completed N=59
Evaluating the Safety and Efficacy of Romidepsin in Combination With Antiretroviral Therapy in HIV-Infected Adults With Suppressed Viral Load
Source: ClinicalTrials.gov NCT01933594 ↗Enrolled (actual)
59
Serious AEs
1.7%
Results posted
May 2019
Primary outcomePrimary: Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohorts 1-3 Romidepsin Arms — 0 proportion of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohorts 1-3 Romidepsin Arms |
— | — |
| PRIMARY Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohort 4 Romidepsin Arm |
0.077 | — |
| PRIMARY Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3 |
-0.02; 0.14; 0; 0.27; 0; 0.27 | 0.44 |
| PRIMARY Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4 |
0; 0.82 | 0.029 sig |
| PRIMARY Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T-cells in Cohorts 1-3 |
-.009; 0 | 0.37 |
| PRIMARY Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4 |
-0.26; -0.16 | 0.54 |
| SECONDARY Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3 |
-0.02; 0.14; 0; 0.27; 0; 0.27 | 0.44 |
| SECONDARY Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4 |
0; 0.82 | 0.029 sig |
| SECONDARY Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T Cells in Cohorts 1-3 |
0.02; -0.05 | 0.96 |
| SECONDARY Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4 |
-0.26; -0.16 | 0.54 |
| SECONDARY Change From Baseline in Histone Acetylation (Median FITC Ac-Histone) in CD3+ Cells in Cohorts 1-3 |
-7; -194 | — |
| SECONDARY Change From Baseline in Histone Acetylation in (Median FITC Ac-histone) in CD3+ Cells in Cohort 4 |
2402; 749; 2774; 8497; 4741; 4741 | 0.19 |
| SECONDARY Change From Baseline in Total HIV-1 DNA in Resting or Total CD4 T Cells in Cohorts 1-3 |
-0.04; 0.05; -0.01; -0.05 | 0.73 |
| SECONDARY Change From Baseline in Total HIV-1 DNA in PBMCs in Cohort 4 |
-0.06; -0.04; -0.13; -0.11; -0.13; -0.07 | 0.8 |
| SECONDARY PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Efavirenz, Dolutegravir, or Raltegravir) in Cohorts 1-3 |
NA; NA; NA; 12; 75.2; 89 | — |
| SECONDARY PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Dolutegravir or Raltegravi) in Cohort 4 |
207; 69; NA; 134; 906; 567 | — |
| SECONDARY HIV-1 RNA Levels in Cohorts 1-3 |
11; 12; 12; 7; 1; 0 | — |
| SECONDARY HIV-1 RNA Levels in Cohort 4 |
13; 2; 0; 0; 8; 3 | — |
| SECONDARY Number of Participants With Reported Grade 2-4 AEs in Cohorts 1-3 |
4; 2; 1; 1 | — |
| SECONDARY Number of Participants With Reported Grade 2-4 AEs in Cohort 4 |
5; 0 | — |
| SECONDARY Change From Baseline in CD4+ and CD8+ T Cell Percent in Cohorts 1-3 |
— | — |
| SECONDARY Change From Baseline in CD4+ T Cell Percent in Cohort 4 |
-2.5; -2; -4.5; 0.5; -3.5; 1 | 0.34 |
| SECONDARY Change From Baseline in CD8+ T Cell Percent in Cohort 4 |
— | — |
| SECONDARY Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohorts 1-3 |
0.5; 0.4; 1; -1; 1.2; -1.4 | 0.95 |
| SECONDARY Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohorts 1-3 |
0.1; 0.3; 0.8; -1.3; 0.3; -0.1 | 0.89 |
| SECONDARY Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohorts 1-3 |
0; 0; 0; 0; 0; 0 | 0.71 |
| SECONDARY Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohorts 1-3 |
0; 0; 0; 0; 0; 0 | 1 |
| SECONDARY Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohort 4 |
0.2; 0.5; 1; 2; 0.4; 0.7 | 1 |
| SECONDARY Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohort 4 |
0.6; 0.2; 1.1; 1.1; -0.3; 2.8 | 0.63 |
| SECONDARY Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohort 4 |
0; -0.1; 0; -0.1; 0; -0.1 | 0.62 |
| SECONDARY Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohort 4 |
0; 0; 0; -0.1; 0; 0 | 0.28 |
| SECONDARY Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3 |
0.2; 1.2; 0.6; 0; 1.2; -1.3 | 0.13 |
| SECONDARY Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3 |
-0.1; 1.8; 0.3; -1.1; 0.9; -1.9 | 0.13 |
| SECONDARY Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4 |
0.5; -1.4; -2; 0.9; 0.3; 0.1 | 0.7 |
| SECONDARY Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4 |
0.1; -4.1; -2.5; -.6; 0.9; -0.8 | 0.78 |
| SECONDARY Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD4+ T-cells in Cohorts 1-3 |
20; 19.3; 18.1; 6 | 0.69 |
| SECONDARY Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD8+ T-cells in Cohorts 1-3 |
16.5; 3.8; 26.5; 25.3 | 0.81 |
| SECONDARY Change From Baseline in PTEF-b Phosphorylation (pNFKB+%) in CD4+ T-cells in Cohort 4 |
5.04; 0.01; 8.78; 0; 6.39; 0 | 0.37 |
| SECONDARY Change From Baseline in PTEF-b Phosphorylation (pS175+%) in CD4+ T-cells in Cohort 4 |
9.93; -0.01; 17; -0.01; 11; -0.01 | 0.027 sig |
Eligibility Criteria
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 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) 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 11.0 g/dL for women
- Platelet count ≥120,000/mm^3
- CrCl ≥60 mL/min
- Potassium & magnesium within normal limits
- AST (SGOT) 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 vacc
Data sourced from ClinicalTrials.gov (NCT01933594). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.