HIV Infections
Conditions
Brief summary
Participants will receive an infusion of both study drugs (3BNC117-LS and 10-1074-LS) and will discontinue antiretroviral therapy (which is the treatment for HIV) two days later. Participants will receive a second dose of the first study drug (3BNC117-LS) at week 12 if the HIV infection is maintained and participants remain off of antiretroviral therapy. The study hypothesizes that intravenous infusions (which means medication is delivered directly into a participant's vein) of the combination of study drugs will be safe and well tolerated, will maintain control of the HIV infection without antiretroviral therapy, and may be associated with a decrease in HIV found in cells that were previously infected with HIV but not actively producing HIV in the body.
Interventions
DRUG3BNC117-LS
3BNC117-LS will be administered by intravenous infusion (directly into the participants vein) over a period of 30 to 60 minutes. The total time needed to administer the study drug may be longer, based on factors such as participant tolerance. The participant's dose will be calculated using their most current weight on record.
DRUG10-1074-LS
10-1074-LS will be administered by intravenous infusion (directly into the participants vein) over a period of 30 to 60 minutes. The total time needed to administer the study drug may be longer, based on factors such as participant tolerance. The participant's dose will be calculated using their most current weight on record.
Sponsors
Rockefeller University
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, single-arm, multi-step study
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Step 0 Inclusion Criteria: 1. Ability and willingness of participant to provide informed consent to enter the Screening and Pre-Entry segment of the study. 2. Individuals age ≥18 to ≤70 years. 3. Weight greater than or equal to 50 kg (110 pounds) and less than or equal to 115 kg (253.5 pounds). 4. Documented HIV-1 infection. 5. For participants who can become pregnant, a negative pregnancy test at Screening must be obtained. 6. For participants who can become pregnant, participant must agree to use two methods of contraception. 7. Participants who can impregnate a partner and who are engaging in sexual activity that could lead to pregnancy must agree to use condoms from 10 days prior to the first dose of study drugs, while receiving the study drugs, and for 12 months after the last dose of study drug to avoid impregnating a partner who can get pregnant. 8. Willingness to use barrier protection (male or female) during sexual activity. Step 0
Exclusion criteria
1\. Currently breastfeeding or pregnancy. Step 1 Inclusion Criteria: 1. On stable suppressive Antiretroviral Therapy (ART) for at least 48 weeks prior to Step 1 study entry with no interruption of ART for 7 consecutive days or longer in the 48 weeks prior to entry in Step 1. 2. If on an NNRTI-based regimen, willing to switch to an integrase inhibitor-based regimen at least 4 weeks prior to discontinuing ART. 3. CD4+ cell count \>450 cells/µL obtained within 90 days prior to study Step 1 entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent. 4. CD4+ cell % ≥15% obtained within 90 days prior to study Step 1 entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent. 5. Nadir CD4+ cell count ≥200 cells/µL. (NOTE: If documentation is not available, then participant recall is acceptable.) 6. Plasma HIV-1 RNA levels of \<50 copies/mL for at least 48 weeks prior to Step 1 entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent (NOTE: At least two viral load measurements within 48 weeks prior to the Step 0 screening visit must be available for review. A single plasma HIV-1 RNA \>50 copies/mL but \<200 copies/mL that is followed by an HIV-1 RNA \<50 copies/mL is permitted.) 7. 3BNC117-LS IC90 less than 1 mcg/mL and MPI \>98% in PBMCs or plasma with the Monogram PhenoSense assay. (NOTE: Monogram PhenoSense assay obtained for eligibility to other clinical trials may be used for eligibility.) 8. 10-1074-LS IC90 less than 1 mcg/mL and MPI \>98% in PBMCs or plasma with the Monogram PhenoSense assay. (NOTE: Monogram PhenoSense assay obtained for eligibility to other clinical trials may be used for eligibility.) 9. The following laboratory values obtained within 90 days prior to Step 1 entry by any US laboratory that has a CLIA certification or its equivalent: 1. absolute neutrophil count (ANC) ˃1,000/mm3 2. hemoglobin \>10 g/dL 3. platelet count ˃100,000/mm3 4. eGFR ≥60 mL/min/1.73m2 5. AST (SGOT), ALT (SGPT), and total bilirubin \<1.5 x ULN 6. alkaline phosphatase less than 1.5 x ULN 10. Completion of pre-entry leukapheresis with documentation of at least 1 billion cells of stored PBMC (e.g., ≥20 aliquots of 50,000,000 PBMC). Sites must receive confirmation from the processing lab via phone, email, or fax that specimens have been entered into the ACTG's Laboratory Data Management System (LDMS). 11. For participants who can become pregnant, a negative pregnancy test at Screening must be obtained. Step 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Grade ≥3 systemic AE related to combination of 3BNC117-LS and 10-1074-LS or premature study treatment discontinuation due to an AE (regardless of grade) that is related to combination of 3BNC117-LS and 10-1074-LS. | 72 weeks |
| Viral rebound defined as confirmed HIV-1 RNA >200 copies/mL at or prior to week 24 of ART discontinuation. | 24 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Frequency of induced anti-study drug antibodies (ADA). | 72 weeks |
| CD4+ cell counts (cells/mm3) through entire study follow-up. | 72 weeks |
| Viral suppression (defined as plasma HIV-1 RNA levels <50 copies/mL) at and prior to week 24 after ART discontinuation | 24 weeks |
| Actual body exposure to drug after administration of a dose of the drug (known as the Area under the curve (AUC)) of weeks 0-24 for 3BNC117-LS and 10-1074-LS. | 72 weeks |
| Frequency of participants who maintain off ART and do not meet ART resumption criteria by study week. | 72 weeks |
| Frequency of participants who resume ART based virologic or immunologic criteria (i.e. viral load, CD4 cell, or development of severe acute retroviral syndrome). | 72 weeks |
| Concentration of 3BNC117-LS and 10-1074-LS at the time of viral rebound. | 72 weeks |
| Viral rebound defined as confirmed HIV-1 RNA>200 copies/mL by week 12 and through Step 2. | 72 weeks |
| Actual body exposure to drug after administration of a dose of the drug (known as the Area under the curve (AUC)) of weeks 0-infinity for 3BNC117-LS and 10-1074-LS. | 72 weeks |
Countries
United States
Outcome results
None listed