Skip to main content
UK clinical trials - updated daily from ClinicalTrials.gov
TrialConnect
← Back to Search
Looking for participantsPhase2

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

Sponsor: Imperial College London

NCT ID: NCT04319367

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
Investigational Medicinal Product (drug)
How long the study runs
Study runs about 74 months (dates as stated)
About the drug or intervention
Investigational Medicinal Product — drug: Recombinant human monoclonal antibody (mAb) or placebo
Patient visit burden
Not specified by the sponsor

In plain English

This trial, run by Imperial College London, is testing whether two long-acting laboratory-made antibodies against HIV (called broadly neutralising antibodies, or bNAbs) can help people living with HIV when added to their standard HIV treatment (antiretroviral therapy, or ART). People who join are chosen at random (by chance) to receive either the antibodies or a placebo (a dummy infusion with no active medicine). The placebo-controlled design means neither the researchers nor participants choose which group they go into.

Who can take part

  • Adults aged 18 to 60
  • Able to give written informed consent, including agreeing to long-term follow-up
  • Willing and able to attend visits and give blood samples
  • Started HIV treatment within six months of when they were first estimated to have caught HIV, based on specific test results — or started treatment early in infection, have never had a CD4 count (a type of immune cell) below 500, and have had an undetectable HIV viral load for at least one year on stable treatment (one reading between 50 and 500 copies/mL in that time is allowed)
  • No signs that the virus is insensitive to the two antibodies used (10-1074 or 3BNC117), based on a gene-sequencing test
  • Negative tests for hepatitis B and hepatitis C
  • No major other health conditions
  • Lowest-ever CD4 count above 250 for those diagnosed with early (primary) HIV infection
  • Current CD4 count above 500, or a CD4 to CD8 ratio above 1
  • On certain types of standard HIV treatment (an integrase inhibitor or boosted protease inhibitor based regimen); if previously on a different type (an NNRTI), must have switched at least 4 weeks before joining
  • Good enough haemoglobin (iron) levels in the blood (at least 12 g/dL for males, 11 g/dL for females)
  • Weigh at least 50 kg
  • Vaccinated against COVID-19 at least 4 weeks before joining
  • If able to become pregnant, must use contraception (hormonal, a coil, or complete abstinence) from 2 weeks before the first infusion until 20 months after the last infusion

Who may not be able to

  • Past heart disease such as heart attack, angina, or stroke
  • Any current or past cancer, apart from certain skin cancers (squamous cell skin cancers are allowed)
  • An ongoing infection or other health condition likely to cause problems during the trial, such as malabsorption syndromes or autoimmune disease
  • Any reason they cannot take standard recommended HIV combination medicines
  • Infection with HTLV-1 (another virus)
  • A positive COVID-19 test within 72 hours before joining
  • Being at high risk of severe COVID-19, as defined by NHS England guidance (per the participant's doctor)
  • Current or planned treatment that suppresses the immune system (inhaled or skin steroid treatments are allowed)
  • Taking part in another trial of an experimental medicine, or any study needing extra blood draws (observational studies are allowed)
  • Past severe allergic reactions (anaphylaxis) or bad reactions to antibody infusions, or allergy to the trial antibodies or their ingredients
  • Planned treatment with IV immunoglobulin or other monoclonal antibody treatments during the trial
  • Certain abnormal blood test results at screening, including serious liver problems, raised liver enzymes (ALT over 5 times the normal limit), reduced kidney function (eGFR under 60), protein in the urine, or abnormal clotting (INR over 1.5)
  • Physical examination findings that, in the researcher's view, should prevent joining
  • Alcohol or drug use that, in the researcher's view, would stop the person following the study requirements
  • Veins not suitable for the scheduled blood draws
  • Concern that the person may not take precautions to prevent passing HIV to others during a treatment interruption period
  • Pregnancy or breastfeeding

What taking part involves

  • • Random assignment (by chance) to receive either two long-acting HIV-specific broadly neutralising antibodies (bNAbs) or a placebo (dummy infusion)
  • • Receiving the study medicine or placebo by infusion (drip) into a vein
  • • Continuing or adjusting standard HIV treatment (ART) — participants must be on an integrase inhibitor or boosted protease inhibitor based regimen
  • • A period of treatment interruption is mentioned as part of the study; further details of what happens during it: Not stated — ask the trial team

Time commitment: Taking part involves attending scheduled visits, regular blood sampling, receiving infusions of the antibodies or placebo, and long-term follow-up; the total trial duration and number of visits: Not stated — ask the trial team.

Plain-English summary (AI-generated) from registry data. Not eligibility advice — only the trial team can confirm whether you can take part. Use the eligibility checker to see how your health profile matches this trial.

Type of study
Testing a treatment
Ages
18 Years to 60 Years
Who
All
Number of participants
72
Started
2021-05-17
Last checked
2024-04

Plain English Summary

What is this study?

  • • Testing a new treatment for hiv/aids and infections
  • • Phase2 - 72 participants
  • • RIO is a placebo-controlled double-blinded two arm prospective phase II randomised controlled trial

Who can take part?

  • • Ages 18 Years to 60 Years
  • • Diagnosed with hiv/aids and infections

Where?

  • • Brighton - University Hospitals Sussex NHS Foundation Trust
  • • Edinburgh - Western General Hospital
  • • London - Imperial College NHS Healthcare Trust
  • • London - Barts Health NHS Trust
  • • +7 more UK sites

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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).

More detail

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.

HIV/AIDS and Infections

How this trial compares with your answers

Answer 2 more questions to improve match

What we know so far

Condition· Matched your search
Age· Tell us your age for better matching
Gender· Tell us your sex for better matching

Still need:

  • • Tell us your age for better matching
  • • Tell us your sex for better matching

Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 18 Years - 60 Years
  • Who can join: All genders

Biomarkers mentioned

documented negativethe negativeand positiveof a positivewithout a negativeof a negativeCD4RNA negative

What the study is looking for

  • ✓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...
  • ✓The date of a positive p24 antigen result with or without a negative HIV antibody test depending on local laboratory...

Who cannot take part

  • ✗Previous ischaemic heart disease (ST or non-ST myocardial infarction, Q3-risk \> 20, stable angina, unstable angina,...
  • ✗Any current or past history of cancer, excluding squamous cell skin cancers
  • ✗Concurrent opportunistic infection or other other health condition or other health condition likely to occur during the trial e.g....
  • ✗Any safety concern to receipt of BHIVA recommended combination antiretrovirals
  • ✗HTLV-1 co-infection
See the full 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 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 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) - 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 2. The date of a positive p24 antigen result with or without a negative HIV antibody test depending on local laboratory reports 3. The date of a 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). 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. 5. The date of a weakly reactive or equivocal 4th generation HIV antibody antigen test 6. 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. 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 (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 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

Where Is This Study? (11 UK sites)

University Hospitals Sussex NHS Foundation Trust

Brighton, United Kingdom

Recruiting
Site contact (verified)
Amanda ClarkePrincipal Investigator

Western General Hospital

Edinburgh, United Kingdom

Recruiting
Site contact (verified)
Rebecca SutherlandPrincipal Investigator

Imperial College NHS Healthcare Trust

London W2 1NY, United Kingdom

Recruiting
Site contact (verified)
Sarah FidlerPrincipal Investigator

Barts Health NHS Trust

London, United Kingdom

Recruiting
Site contact (verified)
Chloe OrkinPrincipal Investigator

Chelsea And Westminster Hospital NHS Foundation Trust

London, United Kingdom

Recruiting
Site contact (verified)
Marta BoffitoPrincipal Investigator

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Recruiting
Site contact (verified)
Julie FoxPrincipal Investigator

Mortimer Market CNWL Hospital NHS Foundation Trust

London, United Kingdom

Recruiting
Site contact (verified)
Sarah PettPrincipal Investigator

Royal Free London NHS Foundation Trust

London, United Kingdom

Recruiting
Site contact (verified)
Sabine KinlochPrincipal Investigator

St Georges Hospital NHS Foundation Trust

London, United Kingdom

Recruiting
Site contact (verified)
Lisa HamzahPrincipal Investigator

Manchester University NHS Foundation Trust

Manchester, United Kingdom

Recruiting
Site contact (verified)
Alison UrielPrincipal Investigator

Oxford University Hospitals

Oxford, United Kingdom

Recruiting
Site contact (verified)
Paola CicconiPrincipal Investigator

How to Get in Touch

Stephen Fletcher

Sponsor contact

CONTACT

+44 (0) 20 7594 7324 rio_trial@imperial.ac.uk
Data sourced from ClinicalTrials.gov · Last verified: 2024-04