Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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.
 
ClinicalTrials.gov Identifier: NCT04319367
Recruitment Status : Not yet recruiting
First Posted : March 24, 2020
Last Update Posted : March 30, 2020
Sponsor:
Collaborators:
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 propose 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.

Layout table for study information
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.
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : October 2024

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. The aim is to measure the efficacy/response of dual broadly neutralising antibodies (bNAb -10-1074-LS and 3BNC117-LS) administered intravenously following initial Antiretroviral Therapy (ART) treatment interruption compared with placebo infusion. [ Time Frame: up to 36 weeks ]
    Virological control will be assessed in participants infused with broadly neutralising antibodies and placebo.


Secondary Outcome Measures :
  1. Safety of dual bNAb infusion of 10-1074-LS and 3BNC117-LS [ Time Frame: Through study completion, an average of 4.0 years ]
    Number of Participants with dual bNAb infusion related Adverse Events, Serious Adverse Events (SAEs), Severity, and will assess relationship to study IMPs.


Other Outcome Measures:
  1. Elucidate the mechanisms by which broadly neutralising antibodies infusions can induce sustained virological control after stopping ART. [ Time Frame: Baseline, Week 12, 24, 36, 48 ]
    HIV-specific humoral, cell-mediated and innate immune responses will be assessed by flow cytometry and the enzyme-linked immune absorbent spot . Full length HIV sequencing and HIV integration site analysis to understand viral reservoir.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 4 weeks 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 PCR) or HCV (Ag or PCR) 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
  • 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, Q-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
  • 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 Child-Pugh classification
    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 ClinicalTrials.gov identifier (NCT number): NCT04319367


Contacts
Layout table for location contacts
Contact: Ambreen Ashraf, Ph.D 020 7594 9451 rio_trial@imperial.ac.uk
Contact: Daphne Babalis, Ph.D +44 20 7594 3403 rio_trial@imperial.ac.uk

Sponsors and Collaborators
Imperial College London
Bill and Melinda Gates Foundation
University of Oxford
Rockefeller University
Investigators
Layout table for investigator information
Principal Investigator: Sarah Fidler, MBBS, Ph.D Imperial College London
Publications:

Layout table for additonal information
Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT04319367    
Other Study ID Numbers: 19IC5249
2019-002129-31 ( EudraCT Number )
First Posted: March 24, 2020    Key Record Dates
Last Update Posted: March 30, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual de-identified participant data collected during the trial (including data dictionaries), will be available after publication. Data will be made available to researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal. The study protocol and informed consent form will also be available.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: 6-12 months after study completion.
Access Criteria: Proposals/requests for data should be directed to the Chief Investigator and researchers (or individuals requesting for data) will be asked to sign a data access agreement.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection