HIV infection MedDRA version: 20.1 Level: LLT Classification code 10000808 Term: Acute human immunodeficiency virus type I infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: 3BNC117-LS
Product Code: 3BNC117-LS
Pharmaceutical Form: Solution for infusion
Current Sponsor code: 3BNC117-LS
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equa
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
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 = 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: • 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.;Primary end point(s): Time to viral rebound within 36 weeks after initial ATI, in the absence of detectable ART.;Timepoint(s) of evaluation of this end point: Within 36 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary 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;Timepoint(s) of evaluation of this end point: Baseline, Week 12, 24, 36, 48 | — |
Countries
United Kingdom
Contacts
Public ContactAmbreen Ashraf
Imperial College London
Outcome results
None listed