Clinical Trials

MainTitle

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

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified March 2020 by Imperial College London

Sponsor
Imperial College London

Collaborator
Bill and Melinda Gates Foundation
University of Oxford
Rockefeller University

Information provided by (Responsible Party)
Imperial College London
ClinicalTrials.gov Identifier
NCT04319367

First received: March 2, 2020
Last updated: March 26, 2020
Last Verified: March 2020
History of Changes
Purpose

Purpose

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 Intervention Phase
HIV/AIDS and Infections

Drug : Investigational Medicinal Product
Phase 2

Study Type: Interventional
Study Design: 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.

Further study details as provided by Imperial College London:

Primary Outcome Measures

  • 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:
  • 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:
  • 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.

Estimated Enrollment: 72
Study Start Date: May 2020
Estimated Study Completion Date: October 2024
Estimated Primary Completion Date: November 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 60 Years  
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

contacts and locations

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT04319367

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

Principal Investigator: Sarah Fidler, MBBS, Ph.D Imperial College London
More Information

More Information


Responsible Party: Imperial College London  
ClinicalTrials.gov Identifier: NCT04319367   History of Changes  
Other Study ID Numbers: 19IC5249  
  2019-002129-31  
Study First Received: March 2, 2020  
Last Updated: March 26, 2020  
Individual Participant Data    
Plan to Share IPD: Yes  

Studies a U.S. FDA-regulated Drug Product: No  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
Infection

ClinicalTrials.gov processed this data on July 10, 2020
This information is provided by ClinicalTrials.gov.