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HIV/AIDS and InfectionsPhase 2RIONCT04319367

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

A Phase 2 study testing Investigational Medicinal Product in people with HIV/AIDS and Infections, run by Imperial College London at 12 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
HIV/AIDS and Infections
What is being tested?
Investigational Medicinal Product
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
72 participants
Where
12 sitesin 2 countries
Study dates
17 May 2021to 31 Jul 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
Show all 21Show fewer
  • 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
  • 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.

Who cannot join

  • 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)
Show all 22Show fewer
  • 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
  • uPCR >30 mg/mmol
  • 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

Trial locations and contacts

12 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Stephen Fletcher contact

+44 (0) 20 7594 7324

rio_trial@imperial.ac.uk

12 sites in 2 countries

United Kingdom11 sites, 11 recruiting

  • University Hospitals Sussex NHS Foundation Trust

    Brighton

    Amanda Clarke

    Amanda Clarke

    Recruiting

  • Western General Hospital

    Edinburgh

    Rebecca Sutherland

    Rebecca Sutherland

    Recruiting

  • Imperial College NHS Healthcare Trust

    London, W2 1NY

    Sarah Fidler

    Sarah Fidler

    Recruiting

  • Barts Health NHS Trust

    London

    Chloe Orkin

    Chloe Orkin

    Recruiting

  • Chelsea And Westminster Hospital NHS Foundation Trust

    London

    Marta Boffito

    Marta Boffito

    Recruiting

  • Guy's and St Thomas' NHS Foundation Trust

    London

    Julie Fox

    Julie Fox

    Recruiting

  • Mortimer Market CNWL Hospital NHS Foundation Trust

    London

    Sarah Pett

    Sarah Pett

    Recruiting

  • Royal Free London NHS Foundation Trust

    London

    Sabine Kinloch

    Sabine Kinloch

    Recruiting

  • St Georges Hospital NHS Foundation Trust

    London

    Lisa Hamzah

    Lisa Hamzah

    Recruiting

  • Manchester University NHS Foundation Trust

    Manchester

    Alison Uriel

    Alison Uriel

    Recruiting

  • Oxford University Hospitals

    Oxford

    Paola Cicconi

    Paola Cicconi

    Recruiting

Other trials in United Kingdom

Denmark1 site, 1 recruiting

  • Aarhus University Hospital

    Aarhus

    Ole Schmeltz Søgaard

    Ole Schmeltz Søgaard

    Recruiting

Other trials in Denmark

About this study

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 or Early Stage HIV Infection on Viral Control Off ART

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).

Read the 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.

Being tested
Investigational Medicinal Product
Medical subject headings
Acquired Immunodeficiency Syndrome, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Investigational Medicinal ProductDrug

    Also called 10-1074-LS and 3BNC117-LS

    Recombinant human monoclonal antibody (mAb) or placebo

Study groups in NCT04319367
Study groupRoleWhat they receive
Arm AActive comparatorART plus dual long-acting (LS) broadly neutralising antibodies (bNAbs) infusion followed by intensively monitored Antiretroviral Treatment Interruption (ATI)
Receives: Drug: Investigational Medicinal Product
Arm BPlacebo comparatorART 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.
Receives: Drug: Investigational Medicinal Product

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 20 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2020
  2. Study start17 May 2021
  3. Primary completion31 Jul 2027 (estimated)
  4. Study completion31 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
72 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04319367
Sponsor's protocol ID
19IC5249
Other IDs
2019-002129-31, 2019
Acronym
RIO
Status last verified
Apr 2024
First submitted
2 Mar 2020
Last updated
17 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 28289286

  • 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.

    PubMed 30258136

  • 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.

    PubMed 27338952

  • 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.

    PubMed 23323897

  • 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.

    PubMed 30085241

  • Fumagalli MJ, Kaczynska A, Allombert M, Lopes-Ribeiro A, de Oliveira Silva M, Hernandez BJ, Lavine C, Espinosa SM, Brown H, Box H, Falaschetti E, Cherrill LR, Elliott T, Lee M, Fox J, Pett S, Clarke A, Uriel A, Sogaard O, Sutherland R, Boffito M, Kinloch-Loes S, Orkin C, Collins S, Zacharopoulou P, Robison N, Bittar C, Oliveira T, Gazumyan A, Jankovic M, Seaman MS, Frater J, Caskey M, Fidler S, Nussenzweig MC. Broadly neutralizing antibodies in adult males living with HIV undergoing analytical treatment interruption: secondary and exploratory outcomes of the phase II randomized controlled RIO trial. Nat Med. 2026 Sep 15. doi: 10.1038/s41591-026-04644-8. Online ahead of print.

    PubMed 42744897

  • Lee MJ, Cherrill LR, Zacharopoulou P, Collins S, Fumagalli M, Falaschetti E, Altaf M, Tipoe T, Godakandaarachi P, Fox J, Uriel A, Clarke A, Loes SK, Pett S, Boffito M, Whitlock G, Sogaard OS, Ring K, Mangawa I, Gohil J, Elliott T, Nielsen H, Gunst JD, Orkin C, Sutherland R, Hamzah L, Cicconi P, Taylor GP, Ujetz J, Jahan I, Brown H, Robinson N, Fletcher S, Box H, Seaton KE, Tomaras GD, Ackerman ME, Weiner JA, Kaczynska A, Bittar C, Horowitz J, Nussenzweig MC, Caskey M, Frater J, Fidler S; RIO Study Team. Time to HIV rebound after infusion of long-acting broadly neutralising antibodies 3BNC117-LS and 10-1074-LS and analytical treatment interruption (the RIO trial): a double-blind, randomised, placebo-controlled trial. Lancet HIV. 2026 Aug;13(8):e527-e537. doi: 10.1016/S2352-3018(26)00059-7. Epub 2026 May 27.

    PubMed 42202839

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Investigational Medicinal Product in people with HIV/AIDS and Infections, run by Imperial College London at 12 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United Kingdom, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Stephen Fletcher (+44 (0) 20 7594 7324, rio_trial@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to viral rebound within 20 weeks after initial ATI (time frame: up to 20 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04319367, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.

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