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A Randomised Placebo Controlled Trial of ART Plus Dual Long-acting HIV-specific Broadly Neutralising Antibodies (bNAbs). (RIO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04319367
Recruitment Status : Recruiting
First Posted : March 24, 2020
Last Update Posted : July 9, 2021
Bill and Melinda Gates Foundation
University of Oxford
Rockefeller University
Information provided by (Responsible Party):
Imperial College London

Brief Summary:
RIO is a placebo-controlled double-blinded two arm prospective phase II randomised controlled trial . This study will test the use of broadly neutralising antibodies (bNAbs) in participants with treated primary HIV infection (PHI).

Condition or disease Intervention/treatment Phase
HIV/AIDS and Infections Drug: Investigational Medicinal Product Phase 2

Detailed Description:

This study proposes a trial of a novel combination of long-acting broadly neutralising antibodies in participants initiating ART early after HIV acquisition, during primary HIV infection (PHI). The aim of this study is to investigate the effect of dual long-acting versions of bNABs (3BNC117-LS and 10-1074-LS) in a randomised clinical trial powered to answer the question whether these bNAbs are effective at controlling HIV replication in the absence of ART.

The study aims to enrol 72 individuals across multiple UK collaborating clinical centres. Participants will have been previously diagnosed with primary HIV-1 infection, will have started ART during early phase of Primary HIV infection, and who have remained on suppressive ART without interruption for at least 12 months. Study duration will vary by participant, depending on the time to viral rebound.

The results from this trial will demonstrate whether or not the combination of two long-acting (LS) broadly neutralising antibodies, 3BNC117-LS and 10-1074-LS, will prevent HIV viral rebound after stopping antiretroviral therapy for an extended period of time in adults living with HIV who initiated ART during early HIV infection.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Placebo Controlled Trial of ART Plus Dual Long-acting HIV-specific Broadly Neutralising Antibodies (bNAbs) vs ART Plus Placebo in Treated Primary HIV Infection on Viral Control Off ART.
Actual Study Start Date : May 17, 2021
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : March 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: Arm A
ART plus dual long-acting (LS) broadly neutralising antibodies (bNAbs) infusion followed by intensively monitored Antiretroviral Treatment Interruption (ATI)
Drug: Investigational Medicinal Product
Recombinant human monoclonal antibody (mAb) or placebo
Other Name: 10-1074-LS and 3BNC117-LS

Placebo Comparator: Arm B
ART plus placebo infusion followed by an ATI (control arm). On re-starting ART, participants will receive immediate dual LS bNAbs and then a second ATI 24 weeks after bNAb infusion.
Drug: Investigational Medicinal Product
Recombinant human monoclonal antibody (mAb) or placebo
Other Name: 10-1074-LS and 3BNC117-LS

Primary Outcome Measures :
  1. Time to viral rebound within 36 weeks after initial ATI [ Time Frame: up to 36 weeks ]
    Virological control will be assessed in participants infused with broadly neutralising antibodies compared to placebo.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Aged ≥18 to ≤60 years old at screening
  • Able to give informed written consent including consent to long-term follow-up
  • Willing and able to comply with visit schedule and provide blood sampling
  • Started ART within maximum of 3 months of confirmed primary HIV infection, based on one of the following six criteria

    1. Positive HIV-1 serology within a maximum of 24 weeks of a documented negative HIV-1 serology test result (can include point of care test (POCT) using blood for both tests)
    2. A positive p24 antigen result and a negative HIV antibody test
    3. Negative antibody test with either detectable HIV RNA or proviral DNA
    4. PHE RITA test algorithm reported as "Incident" confirming the HIV-1 antibody avidity is consistent with recent infection (within the preceding 16 weeks).
    5. Weakly reactive or equivocal 4th generation HIV antibody antigen test
    6. Equivocal or reactive antibody test with <4 bands on western blot
  • Stable on ART with suppressed undetectable HIV VL 'target not detected' (TND) using local assays for >= 1 years
  • No evidence of viral insensitivity to either 10-1074 or 3BNC117 antibodies based on proviral sequencing algorithm
  • HBV sAg or HBV DNA, HCV Ag or HCV RNA negative or anti-core antibody negative
  • No significant co-morbidities
  • Nadir CD4 > 350 cells/µL
  • Current CD4 count > 500 cells/µL or CD4:CD8 ratio >1
  • On integrase inhibitor (INSTI) or boosted protease inhibitor (PI) based regimen at time of randomisation, if previously on non-nucleoside reverse transcriptase inhibitor (NNRTI) has switched at least 4 weeks prior to randomisation
  • Adequate haemoglobin (Hb≥12 g/dL for males, ≥11 g/dL for females)
  • Weight ≥50 kg
  • Have been vaccinated against coronavirus (COVID-19), at least 4 weeks prior to enrolment
  • Females capable of becoming pregnant* must agree to use hormonal contraception, intrauterine device, intrauterine hormone-releasing system, or to complete abstinence** from at least two weeks before the first bNAb/placebo infusion and for 20 months after the last bNAb infusion.

Exclusion Criteria:

  • Previous ischaemic heart disease (ST or non-ST myocardial infarction, Q3-risk > 20, stable angina, unstable angina, stroke)
  • Any current or past history of malignancy, excluding squamous cell skin cancers
  • Concurrent opportunistic infection or other comorbidity or comorbidity likely to occur during the trial e.g. malabsorption syndromes, autoimmune disease
  • Any contraindication to receipt of BHIVA recommended combination antiretrovirals
  • HTLV-1 co-infection
  • SARS-Cov-2 infection confirmed by SARS-Cov-2 RT-PCR positive result from nasopharyngeal swab up to 72 hours prior to randomisation/dosing visit
  • Individuals at high risk from severe COVID-19 disease who maybe defined in accordance with NHSE guidance as vulnerable and shielded (as per the view of participant's physician)
  • Current or planned systemic immunosuppressive therapy (inhaled or topical corticosteroids are allowed)
  • Participation in any other clinical trial of an experimental agent or any non-interventional study where additional blood draws are required; participation in an observational studies is permitted
  • History of anaphylaxis or severe adverse reaction to antibody infusions, or hypersensitivity to 3BNC117-LS or 10-1074-LS or to or any constituent products or excipients thereof
  • Treatment with IV immunoglobulin or other monoclonal antibody treatments planned during the duration of the trial
  • Clinically significant abnormal blood test results at screening including

    1. Moderate to severe hepatic impairment as defined by significant liver impairment with evidence of advanced fibrosis or cirrhosis with decompensation
    2. ALT >5 x ULN
    3. eGFR <60
    4. uPCR >30 mg/mmol
    5. INR >1.5
  • Physical examination findings: Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination and/or vital signs that the investigator believes is a preclusion from enrolment into the study.
  • Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate adherence with study requirements
  • Insufficient venous access that will allow scheduled blood draws as per protocol
  • Concern regarding likelihood of participant not taking precautions to prevent HIV transmission during treatment interruption period
  • Pregnancy or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04319367

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Contact: Daphne Babalis +44 20 7594 3403

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United Kingdom
Imperial College NHS Healthcare Trust Recruiting
London, United Kingdom, W2 1NY
Contact: Sarah Fidler         
Principal Investigator: Sarah Fidler         
Sponsors and Collaborators
Imperial College London
Bill and Melinda Gates Foundation
University of Oxford
Rockefeller University
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Principal Investigator: Sarah Fidler, MBBS, Ph.D Imperial College London

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Responsible Party: Imperial College London Identifier: NCT04319367    
Other Study ID Numbers: 19IC5249
2019-002129-31 ( EudraCT Number )
First Posted: March 24, 2020    Key Record Dates
Last Update Posted: July 9, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Final versions of the anonymised databases, data files, including data dictionaries will be made available to the wider research community after publication.

Data will be made available to researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal.

Imperial College London retains copyright of the databases and data files. A Data User Agreement must be signed before access to the data is permitted.

Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: 12-18 months after study completion.
Access Criteria: Proposals/requests for data should be directed to the Chief Investigator and researchers. Individuals requesting for data will be asked to sign a data access agreement.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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