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

NCT04319367 | Recruiting Phase 2 DMC

• 2 other identifiers: 19IC52492019-002129-31
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 12

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).

Conditions

HIV/AIDS and Infections

Outcome Measures

Primary Outcomes (1)

• Time to viral rebound within 20 weeks after initial ATI

  Virological control will be assessed in participants infused with broadly neutralising antibodies compared to placebo.

  up to 20 weeks

Study Arms (2)

Arm A

ACTIVE COMPARATOR

ART plus dual long-acting (LS) broadly neutralising antibodies (bNAbs) infusion followed by intensively monitored Antiretroviral Treatment Interruption (ATI)

Drug: Investigational Medicinal Product

Arm B

PLACEBO COMPARATOR

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

Interventions

Investigational Medicinal Product DRUG

Recombinant human monoclonal antibody (mAb) or placebo

Also known as: 10-1074-LS and 3BNC117-LS

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 a maximum of six months of estimated time of primary infection. Estimated time of primary infection will be based on one of the following six criteria
• 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) - The estimated time of infection is taken as the midpoint between the dates of the negative HIV-1 serology or POCT test and positive HIV test at diagnosis
• The date of a positive p24 antigen result with or without a negative HIV antibody test depending on local laboratory reports
• The date of a negative antibody test with either detectable HIV RNA or proviral DNA
• PHE RITA test algorithm reported as "Incident" confirming the HIV-1 antibody avidity is consistent with recent infection (within the preceding 16 weeks). The estimated date of infection is assumed to be two months prior to the date of the incident test result. Asanté™ HIV-1 Rapid Recency® Assay can also be used for recency testing.
• The date of a weakly reactive or equivocal 4th generation HIV antibody antigen test
• Equivocal or reactive antibody test with \<4 bands on western blot
• OR, started ART in early stage infection, with nadir CD4 \> 500 cells and stable on ART with suppressed undetectable HIV VL 'target not detected' (TND) using local assays for \>= 1 years (a single viral load measurement \> 50 but \< 500 copies/mL during this time period is allowable)
• 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 \> 250 cells/μL for those diagnosed with confirmed PHI

You may not qualify if:

• 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 (as per current local NHS guidelines or until such guidelines/practices are no longer applicable/relevant)
• 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
• Moderate to severe hepatic impairment as defined by significant liver impairment with evidence of advanced fibrosis or cirrhosis with decompensation
• ALT \>5 x ULN
• eGFR \<60

Sponsors & Collaborators

• Imperial College London: lead
• Bill and Melinda Gates Foundation: collaborator
• University of Oxford: collaborator
• Rockefeller University: collaborator

Study Sites (12)

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

University Hospitals Sussex NHS Foundation Trust

Brighton, United Kingdom

RECRUITING

Western General Hospital

Edinburgh, United Kingdom

RECRUITING

Imperial College NHS Healthcare Trust

London, W2 1NY, United Kingdom

RECRUITING

Barts Health NHS Trust

London, United Kingdom

RECRUITING

Chelsea And Westminster Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

RECRUITING

Mortimer Market CNWL Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

Royal Free London NHS Foundation Trust

London, United Kingdom

RECRUITING

St Georges Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

Manchester University NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Oxford University Hospitals

Oxford, United Kingdom

RECRUITING

Related Publications (5)

• Nishimura Y, Gautam R, Chun TW, Sadjadpour R, Foulds KE, Shingai M, Klein F, Gazumyan A, Golijanin J, Donaldson M, Donau OK, Plishka RJ, Buckler-White A, Seaman MS, Lifson JD, Koup RA, Fauci AS, Nussenzweig MC, Martin MA. Early antibody therapy can induce long-lasting immunity to SHIV. Nature. 2017 Mar 23;543(7646):559-563. doi: 10.1038/nature21435. Epub 2017 Mar 13.

  PMID: 28289286 BACKGROUND

• Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, Lehmann C, Suarez I, Oliveira TY, Lorenzi JCC, Cohen YZ, Wyen C, Kummerle T, Karagounis T, Lu CL, Handl L, Unson-O'Brien C, Patel R, Ruping C, Schlotz M, Witmer-Pack M, Shimeliovich I, Kremer G, Thomas E, Seaton KE, Horowitz J, West AP Jr, Bjorkman PJ, Tomaras GD, Gulick RM, Pfeifer N, Fatkenheuer G, Seaman MS, Klein F, Caskey M, Nussenzweig MC. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018 Sep;561(7724):479-484. doi: 10.1038/s41586-018-0531-2. Epub 2018 Sep 26.

  PMID: 30258136 BACKGROUND

• Scheid JF, Horwitz JA, Bar-On Y, Kreider EF, Lu CL, Lorenzi JC, Feldmann A, Braunschweig M, Nogueira L, Oliveira T, Shimeliovich I, Patel R, Burke L, Cohen YZ, Hadrigan S, Settler A, Witmer-Pack M, West AP Jr, Juelg B, Keler T, Hawthorne T, Zingman B, Gulick RM, Pfeifer N, Learn GH, Seaman MS, Bjorkman PJ, Klein F, Schlesinger SJ, Walker BD, Hahn BH, Nussenzweig MC, Caskey M. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016 Jul 28;535(7613):556-60. doi: 10.1038/nature18929. Epub 2016 Jun 22.

  PMID: 27338952 BACKGROUND

• SPARTAC Trial Investigators; Fidler S, Porter K, Ewings F, Frater J, Ramjee G, Cooper D, Rees H, Fisher M, Schechter M, Kaleebu P, Tambussi G, Kinloch S, Miro JM, Kelleher A, McClure M, Kaye S, Gabriel M, Phillips R, Weber J, Babiker A. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med. 2013 Jan 17;368(3):207-17. doi: 10.1056/NEJMoa1110039.

  PMID: 23323897 BACKGROUND

• Namazi G, Fajnzylber JM, Aga E, Bosch RJ, Acosta EP, Sharaf R, Hartogensis W, Jacobson JM, Connick E, Volberding P, Skiest D, Margolis D, Sneller MC, Little SJ, Gianella S, Smith DM, Kuritzkes DR, Gulick RM, Mellors JW, Mehraj V, Gandhi RT, Mitsuyasu R, Schooley RT, Henry K, Tebas P, Deeks SG, Chun TW, Collier AC, Routy JP, Hecht FM, Walker BD, Li JZ. The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies. J Infect Dis. 2018 Nov 5;218(12):1954-1963. doi: 10.1093/infdis/jiy479.

  PMID: 30085241 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Infections

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Sarah Fidler, MBBS, Ph.D

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen Fletcher

CONTACT

+44 (0) 20 7594 7324; rio_trial@imperial.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 24, 2020
• Study Start: May 17, 2021
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

DK (1); GB (11)