Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-002129-31
    Sponsor's Protocol Code Number:19IC5249
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2019-09-26
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2019-002129-31
    A.3Full title of the trial
    The RIO Trial: 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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The RIO Trial: 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
    A.3.2Name or abbreviated title of the trial where available
    The RIO Trial
    A.4.1Sponsor's protocol code number19IC5249
    A.5.4Other Identifiers
    Name:Funder referenceNumber:OPP1210792
    Name:IRAS IDNumber:266322
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorImperial College London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBill & Melinda Gates Foundation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationImperial College London
    B.5.2Functional name of contact pointAmbreen Ashraf
    B.5.3 Address:
    B.5.3.1Street AddressImperial Clinical Trials Unit
    B.5.3.2Town/ cityStadium House
    B.5.3.3Post codeW12 7RH
    B.5.4Telephone number07593516744
    B.5.6E-maila.ashraf@imperial.ac.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product name3BNC117-LS
    D.3.2Product code 3BNC117-LS
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor code3BNC117-LS
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product name10-1074-LS
    D.3.2Product code 10-1074-LS
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor code10-1074-LS
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HIV infection
    E.1.1.1Medical condition in easily understood language
    HIV infection
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10000808
    E.1.2Term Acute human immunodeficiency virus type I infection
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the efficacy of dual bNAb infusion of 10-1074-LS and 3BNC117-LS at sustaining virological control within 36 weeks following initial ATI compared with placebo infusion.
    E.2.2Secondary objectives of the trial
    • To evaluate the safety of dual bNAb infusion of 10-1074-LS and 3BNC117-LS
    • To determine the role of viraemia at the time of bNAb administration in subsequent virological control.
    • To determine the contribution of circulating bNAbs to virological control compared with a sustained impact following antibody elimination.
    • To document the experiences and determine the attitudes of participants to the interventions and the treatment interruption.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    A qualitative sub-study is planned and is included in this amendment. This involves RIO participants, members of staff, Community Advisory Board members (CAB), including CAB not involved in RIO and non-RIO participants being interviewed by a researcher about their experience in the RIO study. This sub-study aims to understand what trial participants hope to achieve through experimental care as opposed to current treatment regimens. (Refer to attached documents)
    E.3Principal inclusion 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 three months of confirmed primary HIV infection, based on one of the following six criteria
    a. 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)
    b. A positive p24 antigen result and a negative HIV antibody test
    c. Negative antibody test with either detectable HIV RNA or proviral DNA
    d. PHE RITA test algorithm reported as “Incident” confirming the HIV-1 antibody avidity is consistent with recent infection (within the preceding 16 weeks).
    e. Weakly reactive or equivocal 4th generation HIV antibody antigen test
    f. 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 HBV DNA, HCV Ag or HCV RNA negative or anti core antibody 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 the duration of the trial.

    *Complete abstinence (defined as refraining from heterosexual intercourse) must be in line with the preferred and usual lifestyle of the participant. Barrier contraception, periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods), withdrawal and progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of action are not acceptable methods of contraception.
    E.4Principal exclusion criteria
    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
    • 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
    • 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
    • Clinically significant abnormal blood test results at screening including
    a. Moderate to severe hepatic impairment as defined by significant liver impairment with evidence of advanced fibrosis or cirrhosis with decompensation
    b. ALT >5 x ULN
    c. eGFR <60
    d. uPCR >30 mg/mmol
    e. 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
    E.5 End points
    E.5.1Primary end point(s)
    Time to viral rebound within 36 weeks after initial ATI, in the absence of detectable ART.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Within 36 weeks
    E.5.2Secondary end point(s)
    For both Stage 1 and Stage 2, these are:

    1. Safety defined as Adverse Events and Serious Adverse Events by group
    2. Length of time undetectable in days following ATI in the absence of detectable ART (Arm A vs B and Arm B Stage 1 AI vs Stage 2 ATI)
    3. CD4 T cell counts and CD4:CD8 ratios at weeks 12, 24, 36 and 48 after randomisation, and 12 weekly until the end of study participation.
    4. Percentage of participants with undetectable VL at weeks 12, 24, 36 and 48 post randomisation (Stage 1; Arm A vs B) and then for Arm B participants post second ATI
    5. Quantitation of proviral HIV DNA and cell associated RNA
    6. Duration of remission by different parameters (eg VL<40, <400, <1000, +/- blips copies HIV per ml)
    7. Time to re-starting ART after start of ATI
    8. Time to undetectable HIV VL after re-starting ART
    9. ART presence in blood during ATI
    10. bNAb levels in blood
    11. bNAb sensitivity/resistance at viral rebound
    12. HIV Quality of Life measure

    TERTIARY / EXPLORATORY ENDPOINTS
    For both Stage 1 and Stage 2, these are:
    1. HIV-specific (humoral and cell-mediated) and innate immune responses
    2. Immune phenotyping and activation/exhaustion
    3. Host gene expression
    4. Viral sequence and integration site analyses
    5. Measures of the HIV reservoir in blood
    E.5.2.1Timepoint(s) of evaluation of this end point
    Baseline, Week 12, 24, 36, 48
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the trial will occur when the final participant has completed the final follow up visit and all trial data, including results of sample analyses, have been captured on the trial database.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days31
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days31
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 72
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state72
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 0
    F.4.2.2In the whole clinical trial 0
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Participants will return to the expected normal treatment at the end of the study: they will be recommended to re-start ART irrespective of HIV viral load.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-11-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-12-12
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 12:34:30 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA