Human Immunodeficiency Virus (HIV)Phase 2ROADMAPNCT02850016
Romidepsin Plus 3BNC117 Phase 2a Study
A Phase 2 study testing 3BNC117 and Romidepsin in people with Human Immunodeficiency Virus (HIV), run by Rockefeller University at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Human Immunodeficiency Virus (HIV)
- What is being tested?
- 3BNC117 and Romidepsin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 6 Jan 2017to 31 Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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:
- Absolute neutrophil count ≤ 1,000 cells/μl
- Hemoglobin < 11 gm/dL
- Platelet count < 125,000 cells/μl
- Alanine Aminotransferase (ALT) ≥ 1.25 x ULN
- Aspartate Aminotransferase (AST) ≥ 1.25 x ULN
- Total bilirubin > 1.0 ULN
- Creatinine > 1.0 ULN
- Any vaccination within 14 days prior to 3BNC117 administration
- Receipt of any therapeutic HIV vaccine in the past
- Receipt of any monoclonal antibody or HDAC inhibitor of any kind in the past.
- Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
The Rockefeller University
New York, New York, 10065
About this study
Official title: A Phase 2a, Randomized Study of Romidepsin With or Without 3BNC117 to Evaluate the Effects on the HIV-1 Reservoir (ROADMAP)
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.
Read the detailed description
This is a randomized interventional phase 2a trial of 3BNC117 and romidepsin in human immunodeficiency (HIV-1) infected patients on ART, conducted as a multi-center study at the Department of Infectious Diseases, Aarhus University Hospital, Denmark, the Rockefeller University Hospital, USA, and the University Hospital of Cologne, Germany.
Participants will be randomized 1:1 in a non-blinded fashion to receive one of two regimens:
- Two treatment cycles each consisting of one 3BNC117 infusion (30mg/kg) + three romidepsin infusions (5mg/m2); or
- Two treatment cycles each consisting of three romidepsin infusions (5mg/m2).
ART will be discontinued 16 weeks after the start of the second treatment cycle (analytical treatment interruption, ATI) and subjects will be monitored weekly for safety and viral rebound. The targeted enrollment is 30 subjects (15 per arm).
Leukapheresis will be performed before and after the two treatment cycles to guarantee sufficient material to investigate changes in the reservoir after the interventions.
The following criteria will require resumption of ART:
- CD4+ T cell-count <350 cells/mm³ (confirmed by repeat measurement)
- 2 consecutive plasma HIV-1 RNA measurements ≥ 200 copies/mL or above their setpoint viremia (if documented)
- Subject request
- Continued ART interruption will, in the opinion of the investigator or study advisers, pose an unacceptable risk to the subject.
If HIV-1 RNA remains undetectable at week 36, subjects will be offered to continue off ART with close monitoring, in conjunction with the subject's primary medical provider, as long as HIV-1 viral rebound does not occur. ART resumption will follow same criteria as detailed above. All subjects will be followed for a total of 48 weeks from enrollment.
- Conditions
- Human Immunodeficiency Virus (HIV)
- Being tested
- 3BNC117, Romidepsin
- Keywords
- Romidepsin, 3BNC117, Broadly neutralizing antibody
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3BNC117Drug
Also called Monoclonal Antibody
Intravenous Infusion of 3BNC117
RomidepsinDrug
Also called HDAC inhibitor
Intravenous Infusion of Romidepsin
| Study group | Role | What they receive |
|---|---|---|
| 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 . Receives: 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 . Receives: Drug: Romidepsin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
The occurrence of adverse events was assessed during each follow up visit. Adverse events of grades 1 or higher were reported.
Measured: 48 weeks
Change in the Size of the Proviral HIV-1 Reservoir
Determined by total HIV-1 DNA and episomal HIV-1 DNA (2-LTR) in circulating total CD4+ T cells at baseline and prior to the ATI period (week 24).
Measured: baseline and week 24
Plasma HIV-1 RNA
As measured by a routine clinical assay (Cobas Taqman; detection limit 20 copies/mL), a transcription mediated amplification (TMA)-based assay (detection limit 12 copies/ml) and/or a single copy assay (detection limit 1-2 copies/mL)
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2016 (estimated)
- Study start6 Jan 2017
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency Virus (HIV)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rockefeller University
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital of Cologne, Aarhus University Hospital
- Responsible party
- Sponsor
- Investigators
- Marina Caskey, MD, Principal investigator, Rockefeller University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02850016
- Sponsor's protocol ID
- MCA-0896
- Acronym
- ROADMAP
- Status last verified
- Jul 2022
- First submitted
- 26 Jul 2016
- Last updated
- 14 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 35544074Valente 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.
PubMed 32838558
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Randomized Study of Romidepsin With or Without 3BNC117 to Evaluate the Effects on the HIV-1 Reservoir (ROADMAP)
- ClinicalTrials.gov ID
- NCT02850016
- Acronym / sponsor ID
- ROADMAP / MCA-0896
- Conditions
- Human Immunodeficiency Virus (HIV)
- Keywords
- Romidepsin, 3BNC117, Broadly neutralizing antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Rockefeller UniversityUniversity, hospital or other
- Collaborators
- University Hospital of Cologne, Aarhus University Hospital
- Study start
- 6 Jan 2017 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 29 Jul 2016 (estimated)
- Results
- Posted 14 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a randomized interventional phase 2a trial of 3BNC117 and romidepsin in human immunodeficiency (HIV-1) infected patients on ART, conducted as a multi-center study at the Department of Infectious Diseases, Aarhus University Hospital, Denmark, the Rockefeller University Hospital, USA, and the University Hospital of Cologne, Germany.
Participants will be randomized 1:1 in a non-blinded fashion to receive one of two regimens:
- Two treatment cycles each consisting of one 3BNC117 infusion (30mg/kg) + three romidepsin infusions (5mg/m2); or
- Two treatment cycles each consisting of three romidepsin infusions (5mg/m2).
ART will be discontinued 16 weeks after the start of the second treatment cycle (analytical treatment interruption, ATI) and subjects will be monitored weekly for safety and viral rebound. The targeted enrollment is 30 subjects (15 per arm).
Leukapheresis will be performed before and after the two treatment cycles to guarantee sufficient material to investigate changes in the reservoir after the interventions.
The following criteria will require resumption of ART:
- CD4+ T cell-count <350 cells/mm³ (confirmed by repeat measurement)
- 2 consecutive plasma HIV-1 RNA measurements ≥ 200 copies/mL or above their setpoint viremia (if documented)
- Subject request
- Continued ART interruption will, in the opinion of the investigator or study advisers, pose an unacceptable risk to the subject.
If HIV-1 RNA remains undetectable at week 36, subjects will be offered to continue off ART with close monitoring, in conjunction with the subject's primary medical provider, as long as HIV-1 viral rebound does not occur. ART resumption will follow same criteria as detailed above. All subjects will be followed for a total of 48 weeks from enrollment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: 3BNC117, Drug: RomidepsinTwo 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 . |
| Group B | Experimental | Drug: RomidepsinTwo treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 . |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3BNC117Also: Monoclonal AntibodyIntravenous Infusion of 3BNC117 | Drug | Group A |
| RomidepsinAlso: HDAC inhibitorIntravenous Infusion of Romidepsin | Drug | Group A, Group B |
Primary outcome
Days to Viral Rebound During Analytical Treatment Interruption (ATI)
Time frame: Week 24 to Week 36
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
3 secondary outcomes
Number of of Adverse Events (AE), Serious Adverse Events (SAE), and Serious Unexpected Serious Adverse Reactions (SUSAR).
Time frame: 48 weeks
Change in the Size of the Proviral HIV-1 Reservoir
Time frame: baseline and week 24
Plasma HIV-1 RNA
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35544074Gruell 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.
- Derived from this study: PubMed 32838558Valente 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marina Caskey, MD principal investigator
Rockefeller University
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 3BNC117 and Romidepsin in people with Human Immunodeficiency Virus (HIV), run by Rockefeller University at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Denmark, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days to Viral Rebound During Analytical Treatment Interruption (ATI) (time frame: Week 24 to Week 36). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02850016, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2022; AzTrials last refreshed its copy on 27 Oct 2026.