TEROPAVIMAB for HIV infection|Primary HIV infection

Inclusion criteria

• {"criterion_text":"- Aged ≥18 to ≤60 years old at screening\n- Current CD4 count > 500 cells/μl or CD4: CD8 ratio >1.0\n- 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\n- Adequate haemoglobin (Hb≥12 g/dL for males, ≥11 g/dL for females)\n- Weight ≥ 50kg\n- Have been vaccinated against coronavirus (COVID-19), at least 4 weeks prior to enrolment\n- 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\n- Able to give informed written consent including consent to long-term follow-up\n- Willing and able to comply with visit schedule and provide blood sampling\n- 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\n- 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)\n- No evidence of viral insensitivity to either 10-1074 or 3BNC117 antibodies based on proviral sequencing algorithm\n- HBV sAg or HBV DNA, HCV Ag or HCV RNA negative or anti core antibody negative\n- No significant co-morbidities\n- Nadir CD4 > 250 cells/μl for those diagnosed with confirmed PHI"}

Exclusion criteria

• {"criterion_text":"- Previous ischaemic heart disease (ST or non-ST myocardial infarction, Q3-risk > 20, stable angina, unstable angina, stroke)\n- 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\n- Treatment with IV immunoglobulin or other monoclonal antibody treatments planned during the duration of the trial\n- 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\n- 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\n- Active alcohol or substance use that, in the Investigator’s opinion, will prevent adequate adherence with study requirements\n- Insufficient venous access that will allow scheduled blood draws as per protocol\n- Concern regarding likelihood of participant not taking precautions to prevent HIV transmission during treatment interruption period\n- Pregnancy or breastfeeding\n- Any current or past history of malignancy, excluding squamous cell skin cancers\n- Concurrent opportunistic infection or other comorbidity or comorbidity likely to occur during the trial e.g. malabsorption syndromes, autoimmune disease\n- Any contraindication to receipt of BHIVA recommended combination antiretrovirals\n- HTLV-1 co-infection\n- 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)\n- 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)\n- Current or planned systemic immunosuppressive therapy (inhaled and topical corticosteroids are allowed)\n- 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"}

Primary endpoints

• {"endpoint_text":"- Time to viral rebound within 20 weeks after initial ATI","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Safety defined as Adverse Events and Serious Adverse Events by group\n- 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)\n- 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.\n- 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\n- Quantitation of proviral HIV DNA and cell associated RNA\n- Duration of remission by different parameters (e.g. VL <40, <400, <1000, +/- blips copies HIV per ml)\n- Time to re-starting ART after start of ATI\n- Time to undetectable HIV VL after re-starting ART\n- ART presence in blood during ATI\n- bNAb levels in blood\n- bNAb resistance/sensitivity\n- HIV Quality of Life measure","definition_or_measurement_approach":""}

Denmark

Earliest CTIS Part Ii Submission Date

13-12-2024

Latest Decision Or Authorization Date

16-05-2025

Processing Time Days

154

Number Of Sites

1

Number Of Participants

6

Germany

Earliest CTIS Part Ii Submission Date

22-08-2025

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

20

Number Of Sites

1

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

27-06-2025

Latest Decision Or Authorization Date

29-09-2025

Processing Time Days

94

Number Of Sites

1

Number Of Participants

5

Netherlands

Earliest CTIS Part Ii Submission Date

25-08-2025

Latest Decision Or Authorization Date

29-09-2025

Processing Time Days

35

Number Of Sites

1

Number Of Participants

3

Sweden

Earliest CTIS Part Ii Submission Date

10-07-2025

Latest Decision Or Authorization Date

03-09-2025

Processing Time Days

55

Number Of Sites

1

Number Of Participants

2

Belgium

Earliest CTIS Part Ii Submission Date

15-09-2025

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

193

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Imperial College London Limited

Organisation Type

Educational Institution

Country Of Registered Address

United Kingdom

Third parties

• {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"sponsorDuties code: 1; contact email gcp@clin.au.dk","organisation_type":"Educational Institution"}