RIO Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Imperial College London Limited

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Virus Diseases [C02]

Trial duration

2 Jan 2025 → ongoing

Decision date (initial)

2025-11-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bill and Melinda Gates Foundation

External identifiers

EU CT number

2024-514564-13-00

EudraCT number

2019-002129-31

ClinicalTrials.gov

NCT04319367

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To determine the efficacy of dual bNAb infusion of 10-1074-LS and 3BNC117-LS at sustaining virological control within 20 weeks following initial ATI compared with placebo infusion.

Secondary objectives 4

1. To evaluate the safety of dual bNAb infusion of 10-1074-LS and 3BNC117-LS.
2. To determine the role of viraemia at the time of bNAb administration in subsequent virological control.
3. To determine the contribution of circulating bNAbs to virological control compared with a sustained impact following antibody elimination.
4. To document the experiences and determine the attitudes of participants to the interventions and the treatment interruption.

Conditions and MedDRA coding

HIV

Study design 3 periods

Regulatory references

Plan to share IPD

Yes

IPD plan description

The investigator must ensure that the participant's confidentiality is maintained. On the CRF or other documents submitted to the Sponsors, participants will be identified by a participant ID number only. Documents that are not submitted to the Sponsor (e.g., signed informed consent form) should be kept in a strictly confidential file by the investigator. The investigator shall permit direct access to participants’ records and source documents for the purposes of monitoring, auditing, or inspection by the Sponsor, authorised representatives of the Sponsor, Regulatory Authorities and RECs. Individual de-identified participant data collected during the trial (including data dictionaries), will be available to share after publication. Data will be made available to researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal. Proposals/requests should be directed to the Chief Investigator and requestors will be asked to sign a data access agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Aged ≥18 to ≤60 years old at screening
2. Able to give informed written consent including consent to long-term follow-up
3. Willing and able to comply with visit schedule and provide blood sampling
4. Started ART within a maximum of six months of estimated time of primary or Early stage infection. Estimated time of primary infection will be 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) – 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. b. The date of a positive p24 antigen result with or without a negative HIV antibody test depending on local lab reporting c. The date of a 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). 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. e. The date of a weakly reactive or equivocal 4th generation HIV antibody antigen test f. The date of an equivocal or reactive antibody test with <4 bands on western blot
5. 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)
6. No evidence of viral insensitivity to either 10-1074 or 3BNC117 antibodies based on proviral sequencing algorithm
7. HBV sAg or HBV DNA, HCV Ag or HCV RNA negative or anti core antibody negative
8. No significant co-morbidities
9. Nadir CD4 > 250 cells/μl for those diagnosed with confirmed PHI
10. Current CD4 count > 500 cells/μl or CD4: CD8 ratio >1.0
11. On integrase inhibitor (INSTI) or boosted protease inhibitor (bPI) based regimen at time of randomisation, if previously on non-nucleoside reverse transcriptase inhibitor (NNRTI) has switched at least 4 weeks prior to randomisation
12. Adequate haemoglobin (Hb≥12 g/dL for males, ≥11 g/dL for females)
13. Weight ≥ 50kg
14. Have been vaccinated against coronavirus (COVID-19), at least 4 weeks prior to enrolment
15. 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/placebo infusion

Exclusion criteria 17

1. Previous ischaemic heart disease (ST or non-ST myocardial infarction, Q3-risk > 20, stable angina, unstable angina, stroke)
2. Any current or past history of malignancy, excluding squamous cell skin cancers
3. Concurrent opportunistic infection or other comorbidity or comorbidity likely to occur during the trial e.g. malabsorption syndromes, autoimmune disease
4. Any contraindication to receipt of BHIVA recommended combination antiretrovirals
5. HTLV-1 co-infection
6. 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)
7. Individuals at high risk from severe COVID-19 disease who may be defined in accordance with NHSE guidance as vulnerable and shielded (as per the view of participant’s physician)
8. Current or planned systemic immunosuppressive therapy (inhaled and topical corticosteroids are allowed)
9. Participation in any other clinical trial of an experimental agent or any non-interventional study where additional blood draws are required; participation in observational studies is permitted
10. History of anaphylaxis or severe adverse reaction to antibody infusions, or hypersensitivity to 3BNC117-LS or 10-1074-LS or to any constituent products or excipients thereof
11. Treatment with IV immunoglobulin or other monoclonal antibody treatments planned during the duration of the trial
12. 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
13. 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
14. Active alcohol or substance use that, in the Investigator’s opinion, will prevent adequate adherence with study requirements
15. Insufficient venous access that will allow scheduled blood draws as per protocol
16. Concern regarding likelihood of participant not taking precautions to prevent HIV transmission during treatment interruption period
17. Pregnancy or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to viral rebound within 20 weeks after initial ATI

Secondary endpoints 12

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 ATI vs Stage 2 ATI)
3. CD4 T cell counts and CD4:CD8 ratios at weeks 12, 20, 32 and 44 after randomisation, and 12 weekly until the end of study (Refer to Section 9.13) 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 (e.g. 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 resistance/sensitivity
12. HIV Quality of Life measure

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Imperial College London Limited

Sponsor organisation

Imperial College London Limited

Address

Paddington, Norfolk Place Norfolk Place

City

London

Postcode

W2 1PG

Country

United Kingdom

Scientific contact point

Organisation

Imperial College London Limited

Contact name

RIO Clinical Trial Manager

Public contact point

Organisation

Imperial College London Limited

Contact name

RIO Clinical Trial Manager

Third parties 1

Locations

6 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications