Romidepsin Plus 3BNC117 Phase 2a Study

NCT02850016 | Completed Phase 2 Results DMC

• 1 other identifier: MCA-0896
• Study Type: interventional
• Target: 48
• Locations: 3 countries
• Sites: 3

Brief Summary

The aim of this protocol is to evaluate the effects of romidepsin plus 3BNC117 or romidepsin alone on delaying or preventing viral rebound in ART-treated HIV-1-infected individuals during an analytical interruption of ART.

Conditions

Human Immunodeficiency Virus (HIV)

Keywords

Romidepsin; 3BNC117; Broadly neutralizing antibody

Outcome Measures

Primary Outcomes (1)

• Days to Viral Rebound During Analytical Treatment Interruption (ATI)

  Viral rebound is defined as HIV-1 RNA ≥ 200 copies/mL on 2 consecutive measurements during ATI. If viral rebound occurs, the date of the first measurement of HIV-1 RNA ≥ 200 copies/mL will be defined as "date of viral rebound

  Week 24 to Week 36

Secondary Outcomes (3)

• Number of of Adverse Events (AE), Serious Adverse Events (SAE), and Serious Unexpected Serious Adverse Reactions (SUSAR).

  48 weeks

• Change in the Size of the Proviral HIV-1 Reservoir

  baseline and week 24

• Plasma HIV-1 RNA

  48 weeks

Other Outcomes (1)

• HIV-1 Transcriptional Activity as Determined by Unspliced HIV-1 RNA (CA usHIV-1 RNA) in Circulating Total CD4+ T Cells.

  baseline and week 24

Study Arms (2)

Group A

EXPERIMENTAL

Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .

Drug: 3BNC117; Drug: Romidepsin

Group B

EXPERIMENTAL

Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .

Drug: Romidepsin

Interventions

3BNC117 DRUG

Intravenous Infusion of 3BNC117

Also known as: Monoclonal Antibody

Group A

Romidepsin DRUG

Intravenous Infusion of Romidepsin

Also known as: HDAC inhibitor

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults age 18-65 years with documented HIV-1 infection
• CD4+ T-cell count \>500 cells/mm3 at screening
• On ART for a minimum of 24 months and HIV-1 RNA plasma level of \< 50 copies/ml by standard assays for at least 18 months (a single viral load measurement \> 50 but \< 500 copies/ml during this time period is allowable).
• Individuals on protease inhibitor or NNRTI-based regimens, or regimens containing cobicistat must be willing to switch to an integrase-inhibitor-based regimen (raltegravir or dolutegravir) prior to enrollment.

You may not qualify if:

• Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the investigators within the last 6 months
• Pregnancy as determined by a positive urine or serum beta-hCG.
• Participant unwilling to use two reliable contraception methods (i.e. condom with spermicide, diaphragm with spermicide, progestin-only containing intrauterine device (IUD) (eg, Mirena, Implanon, Nuva Ring), non-estrogen containing formulations of hormonal birth control drugs with condom) for the study duration.
• Currently breast-feeding.
• History of resistance to 2 or more classes of antiretroviral medications
• Any medical, psychiatric, social, or occupational condition that, as judged by the investigators, would interfere with the evaluation of study objectives (such as severe alcohol or drug abuse, dementia).
• Acute or chronic hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
• A history of AIDS-defining illness within 3 years prior to enrollment.
• History of B-cell lymphoma, including CNS lymphoma
• CD4 nadir \< 200 cells/mm3
• History of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents, or family history of sudden death at age \< 50 years.
• ECG at screening that shows QTc \>450 msec when calculated using the Fridericia formula from either lead V3 or V4, pathological Q-waves (Q-wave \> 40 msec or depth \> 0.4-0.5 mV), evidence of a ventricular pre-excitation syndromes, complete or incomplete LBBB or RBBB, second or third degree heart block, QRS duration \> 120 msec, or bradycardia defined by sinus rate \< 50 bps
• Use of QT-prolonging medication, renal or hepatic disease, structural heart disease or left ventricular dysfunction
• Any symptomatic or asymptomatic arrhythmia excluding sinus arrhythmia and bradycardia ≥ 50 bps.
• Laboratory abnormalities in the parameters listed below:

Sponsors & Collaborators

• Rockefeller University: lead
• University Hospital of Cologne: collaborator
• Aarhus University Hospital: collaborator

Study Sites (3)

The Rockefeller University

New York, New York, 10065, United States

Location

Aarhus University Hospital

Aarhus, Denmark

Location

University of Cologne

Cologne, 50937, Germany

Location

Related Publications (2)

• Gruell H, Gunst JD, Cohen YZ, Pahus MH, Malin JJ, Platten M, Millard KG, Tolstrup M, Jones RB, Conce Alberto WD, Lorenzi JCC, Oliveira TY, Kummerle T, Suarez I, Unson-O'Brien C, Nogueira L, Olesen R, Ostergaard L, Nielsen H, Lehmann C, Nussenzweig MC, Fatkenheuer G, Klein F, Caskey M, Sogaard OS. Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial. Lancet Microbe. 2022 Mar;3(3):e203-e214. doi: 10.1016/S2666-5247(21)00239-1. Epub 2022 Jan 24.

  PMID: 35544074 DERIVED

• Valente PK, Wu Y, Cohen YZ, Caskey M, Meyers K. Behavioral and social science research to support development of educational materials for clinical trials of broadly neutralizing antibodies for HIV treatment and prevention. Clin Trials. 2021 Feb;18(1):17-27. doi: 10.1177/1740774520948042. Epub 2020 Aug 24.

  PMID: 32838558 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

3BNC117 antibody; Antibodies, Monoclonal; romidepsin; Histone Deacetylase Inhibitors

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Marina Caskey
• Organization: The Rockefeller University

mcaskey@rockefeller.edu

212-327-7396

Study Officials

• Marina Caskey, MD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: July 29, 2016
• Study Start: January 6, 2017
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: July 14, 2022
• Results First Posted: July 14, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); DK (1); DE (1)