Early Administration of Romidepsin and 3BNC117 in Treatment-naïve HIV Patients Starting ART

NCT ID: NCT03041012

Last Updated: 2025-04-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-20

Study Completion Date

2022-12-30

Brief Summary

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To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (ART)

Detailed Description

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The study will be conducted among ART naïve HIV-1-infected patients.

Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.

Conditions

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Hiv

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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antiretrovirals

Standard of care

Group Type PLACEBO_COMPARATOR

Antiretrovirals

Intervention Type DRUG

Combination antiretroviral therapy

antiretrovirals + romidepsin

Standard of care + LRA

Group Type ACTIVE_COMPARATOR

Romidepsin

Intervention Type DRUG

5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART

Antiretrovirals

Intervention Type DRUG

Combination antiretroviral therapy

antiretrovirals + 3BNC117

Standard of care + bNAb

Group Type ACTIVE_COMPARATOR

3BNC117

Intervention Type DRUG

30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART

Antiretrovirals

Intervention Type DRUG

Combination antiretroviral therapy

antiretrovirals + romidepsin + 3BNC117

Standard of care + LRA + bNAb

Group Type ACTIVE_COMPARATOR

Romidepsin

Intervention Type DRUG

5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART

3BNC117

Intervention Type DRUG

30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART

Antiretrovirals

Intervention Type DRUG

Combination antiretroviral therapy

Interventions

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Romidepsin

5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART

Intervention Type DRUG

3BNC117

30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART

Intervention Type DRUG

Antiretrovirals

Combination antiretroviral therapy

Intervention Type DRUG

Other Intervention Names

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Istodax Broadly neutralizing antibody ART

Eligibility Criteria

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Inclusion Criteria

* Documented HIV-1 infection
* CD4+ T cell count \>200/µL on last visit prior to study entry
* ART naïve
* Able to give informed consent

Exclusion Criteria

* Any significant acute medical illness (not including primary HIV infection) in the past 8 weeks
* Any evidence of an active AIDS-defining opportunistic infection
* Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy
* The following laboratory values at screening, but the values can be repeated within the screening period, but test results must be available before baseline (day 0) and checked for eligibility:

* Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)
* Serum total bilirubin ≥3 ULN
* Estimated glomerular filtration rate (eGFR) ≤60 mL/min (based on serum creatinine or other appropriate validated markers)
* Platelet count ≤100 x10\^9/L
* Absolute neutrophil count ≤1x10\^9/L
* Serum potassium, magnesium, phosphorus outside ≥1.5 ULN/LLN
* Total calcium (corrected for serum albumin) or ionized calcium ≥1.5 ULN/LLN
* 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
* ECG at screening that shows QTc \>450 ms when calculated using the Fridericia formula from either lead V3 or V4 \[86\]
* Use of:

* Warfarin or warfarin-derivatives
* HDACi
* An agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening
* Drugs that induce or inhibit CYP3A4 or P-gp
* History of:

* Clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)
* Malignancy or transplantation, including skin cancers or Kaposi sarcoma
* Diabetes mellitus
* Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to study entry
* Known resistance to \>2 classes of ART
* Known hypersensitivity to the components of romidepsin, 3BNC117 or their analogues
* Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of non-estrogen containing contraceptions (according to the Danish Medicines Agency guidelines) to avoid pregnancy for the 3 week study period and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays
* Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the 3-week study period, and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rigshospitalet, Denmark

OTHER

Sponsor Role collaborator

Hvidovre University Hospital

OTHER

Sponsor Role collaborator

Odense University Hospital

OTHER

Sponsor Role collaborator

Aalborg University Hospital

OTHER

Sponsor Role collaborator

Herning Hospital

OTHER

Sponsor Role collaborator

Hammersmith Hospitals NHS Trust

OTHER

Sponsor Role collaborator

St Mary's Hospital, London

OTHER

Sponsor Role collaborator

Aarhus University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ole S Søgaard, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital

Locations

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Department of Infectious Diseases

Aalborg, , Denmark

Site Status

Dept. of Infectious Diseases, Aarhus University Hospital

Aarhus, , Denmark

Site Status

Department of Infectious Diseases

Copenhagen, , Denmark

Site Status

Department of Infectious Diseases

Hvidovre, , Denmark

Site Status

Department of Infectious Diseases

Odense, , Denmark

Site Status

Guy's and St Thomas'

London, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

Countries

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Denmark United Kingdom

References

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Gunst JD, Pahus MH, Rosas-Umbert M, Lu IN, Benfield T, Nielsen H, Johansen IS, Mohey R, Ostergaard L, Klastrup V, Khan M, Schleimann MH, Olesen R, Stovring H, Denton PW, Kinloch NN, Copertino DC, Ward AR, Alberto WDC, Nielsen SD, Puertas MC, Ramos V, Reeves JD, Petropoulos CJ, Martinez-Picado J, Brumme ZL, Jones RB, Fox J, Tolstrup M, Nussenzweig MC, Caskey M, Fidler S, Sogaard OS. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. Nat Med. 2022 Nov;28(11):2424-2435. doi: 10.1038/s41591-022-02023-7. Epub 2022 Oct 17.

Reference Type DERIVED
PMID: 36253609 (View on PubMed)

Other Identifiers

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2015-002234-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

eCLEAR-001

Identifier Type: -

Identifier Source: org_study_id

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