- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03254277
3BNC117-LS First-in-Human Phase 1 Study
A Phase 1 First-in-human Study of the Safety and Pharmacokinetics of 3BNC117-LS in HIV-infected and HIV-uninfected Individuals
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The proposed study is a Phase 1, open label, dose escalation cohort study of 3BNC117-LS administered intravenously in HIV-uninfected and HIV-1 infected participants.
This study consists of two parts. In part A, study participants will be enrolled in an open label manner to receive a single intravenous infusion of 3BNC117-LS at one of three increasing dose levels (3 mg/kg, 10 mg/kg and 30 mg/kg). Participants in Part B will also receive a single administration of 3BNC117-LS, however, the product administered in Part B of the study derives from a new manufacturing lot. The manufacturing lot used in Part A had incomplete glycosylation of the 3BNC117-LS light chain, which has been corrected in the new lot. Participants in Part B will receive 3BNC117-LS intravenously at 30 mg/kg in an open label manner (HIV-uninfected and HIV-infected) or will be randomized to receive a subcutaneous injection of 3BNC117-LS or placebo in a double-blinded fashion (HIV-uninfected only).
Part A has already been enrolled with 21 participants. Part B has a planned enrollment of 22 participants.
Part A
- Group 1A (n=3-6) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 3 mg/kg.
- Group 1B (n=3-6) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.
- Group 1C (n=3-6) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
- Group 2B (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.
- Group 2C (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
Part B
- Group 1D (n=3) - HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
- Group 2D (n=3) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
- Group 1E (n=8) - HIV-uninfected individuals will be administered a single 1 mL (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.
- Group 1F (n=8) - HIV-uninfected individuals will be administered a single 2 mL (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.
Following 3BNC117-LS infusion, study participants will return for safety assessments at weeks 1, 2 and 4 following infusion, then bi-monthly or monthly until the end of study follow up.
Serum samples for PK (pharmacokinetic) measurements will be collected before 3BNC117-LS infusion, at the end of the infusion, and at multiple time points during study follow up.
Samples will also be collected for measurement of HIV-1 plasma RNA levels before 3BNC117-LS infusion (screen, pre-infusion and day 0) and at all follow up visits in Groups 2B and 2C.
All participants will be followed for 48 weeks after 3BNC117-LS administration.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10065
- The Rockefeller University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Groups 1A-1F (HIV-uninfected):
- Males and females, age 18 to 65
- Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent with low risk of HIV exposure.
If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.
- Female study participants of reproductive potential are defined as pre-menopausal women who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.
Groups 2B-2D (HIV-infected):
- Males and females, age 18 to 65.
- HIV-1 infection confirmed by two laboratory assays.
- HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml by standard assays (ART-naïve or off ART due to intolerance or by choice), or on ART with HIV-1 plasma RNA levels < 20 copies/ml. HIV-1 RNA levels should be measured on 2 occasions, at least 1 week apart. At least one measurement must be performed within 49 days prior to enrollment (day 0). Group 2D will only enroll HIV-infected individuals on ART.
- Current CD4+ T cell count > 300 cells/μl.
- If sexually active male or female, and participating in sexual activity that could lead to pregnancy or transmission of HIV, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.
Exclusion Criteria:
Groups 1A-1F (HIV-uninfected):
- Confirmed HIV-1 or HIV-2 infection.
- History of immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
- Any clinically significant acute or chronic medical condition (such as autoimmune diseases) that in the opinion of the investigator would preclude participation.
- Within the 12 months prior to enrollment, the participant has a history of sexually transmitted infection.
- Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
Laboratory abnormalities in the parameters listed:
- Absolute neutrophil count ≤ 1,500 cells/µL;
- Hemoglobin ≤ 11 gm/dL if female; ≤ 12.5 gm/dL if male;
- Platelet count ≤ 125,000 cells/µL;
- Alanine transaminase (ALT) ≥ 1.25 x ULN;
- Aspartate transaminase (AST) ≥ 1.25 x ULN;
- Alkaline phosphatase ≥ 1.5 x ULN;
- Total bilirubin > 1 x ULN;
- Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2.
- Pregnancy or lactation.
- Any vaccination within 14 days prior to 3BNC117-LS infusion.
- Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
- History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
- Individuals with known hypersensitivity to any constituent of the investigational product.
- Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.
Groups 2B-2D (HIV-infected):
- Have a history of AIDS-defining illness within 3 years prior to enrollment.
- History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
- Any clinically significant acute or chronic medical condition (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.
- Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
Laboratory abnormalities in the parameters listed below:
- Absolute neutrophil count ≤ 1,000 cells/μl;
- Hemoglobin ≤ 10 gm/dL;
- Platelet count ≤ 100,000 cells/μl;
- ALT ≥ 1.5 x ULN;
- AST ≥ 1.5 x ULN;
- Alkaline phosphatase ≥ 1.5 x ULN;
- Total bilirubin > 1 x ULN;
- eGFR < 60 mL/min/1.73m2.
- Pregnancy or lactation.
- Any vaccination within 14 days prior to 3BNC117-LS infusion.
- Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
- History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
- Individuals with known hypersensitivity to any constituent of the investigational product.
- Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1A
HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 3 mg/kg.
|
Intravenous infusion of 3BNC117-LS
Other Names:
|
Experimental: Group 1B
HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.
|
Intravenous infusion of 3BNC117-LS
Other Names:
|
Experimental: Group 1C
HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
|
Intravenous infusion of 3BNC117-LS
Other Names:
|
Experimental: Group 2B
HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.
|
Intravenous infusion of 3BNC117-LS
Other Names:
|
Experimental: Group 2C
HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
|
Intravenous infusion of 3BNC117-LS
Other Names:
|
Experimental: Group 1D
HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
|
Intravenous infusion of 3BNC117-LS
Other Names:
|
Experimental: Group 2D
HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20 copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.
|
Intravenous infusion of 3BNC117-LS
Other Names:
|
Experimental: Group 1E
HIV-uninfected individuals will be administered a single 1 mL (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.
|
Placebo
Intravenous infusion of 3BNC117-LS
Other Names:
|
Experimental: Group 1F
HIV-uninfected individuals will be administered a single 2 mL (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.
|
Placebo
Intravenous infusion of 3BNC117-LS
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The number of participants who experience adverse events within 2 weeks after 3BNC117-LS infusion in all study groups
Time Frame: 2 weeks following the 3BNC117-LS infusion
|
Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.
|
2 weeks following the 3BNC117-LS infusion
|
Elimination half-life (t1/2) of 3BNC117-LS in all study groups
Time Frame: 48 weeks
|
Elimination half-life (t1/2) of 3BNC117-LS in all study groups
|
48 weeks
|
Clearance (CL/F) of 3BNC117-LS in all study groups
Time Frame: 48 weeks
|
Clearance (CL/F) of 3BNC117-LS in all study groups
|
48 weeks
|
Volume of distribution (Vz/F) of 3BNC117-LS in all study groups
Time Frame: 48 weeks
|
Volume of distribution (Vz/F) of 3BNC117-LS in all study groups
|
48 weeks
|
Area under the curve of 3BNC117-LS in all study groups
Time Frame: 48 weeks
|
Area under the curve of 3BNC117-LS in all study groups
|
48 weeks
|
Decay curve of 3BNC117-LS in all study groups
Time Frame: 48 weeks
|
Decay curve of 3BNC117-LS in all study groups
|
48 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency of induced anti-3BNC117-LS antibodies in all study groups.
Time Frame: 48 weeks
|
Frequency of induced anti-3BNC117-LS antibodies in all study groups.
|
48 weeks
|
Levels of induced anti-3BNC117-LS antibodies in all study groups.
Time Frame: 48 weeks
|
Levels of induced anti-3BNC117-LS antibodies in all study groups.
|
48 weeks
|
The number of participants who experience adverse events during study follow-up
Time Frame: 48 weeks
|
Adverse events include signs, symptoms and laboratory abnormalities
|
48 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
3BNC117-LS levels in cervicovaginal and rectal fluids
Time Frame: Day 0 and 2 weeks following 3BNC117-LS infusion
|
3BNC117-LS levels in cervicovaginal and rectal fluids
|
Day 0 and 2 weeks following 3BNC117-LS infusion
|
The decline in plasma HIV-1 RNA level after 3BNC117-LS infusion in viremic HIV-infected individuals
Time Frame: 48 weeks
|
The decline in plasma HIV-1 RNA level after 3BNC117-LS infusion in viremic HIV-infected individuals
|
48 weeks
|
Analysis of escape viruses in individuals not on ART
Time Frame: 48 weeks
|
Phenotypic and genotypic analysis of escape viruses in individuals not on ART.
|
48 weeks
|
Levels of cell-associated HIV-1 RNA and DNA before and after 3BNC117-LS infusion.
Time Frame: 48 weeks
|
Levels of cell-associated HIV-1 RNA and DNA before and after 3BNC117-LS infusion.
|
48 weeks
|
Serum neutralizing activity against a panel of HIV-1 isolates before and after 3BNC117-LS infusion.
Time Frame: 48 weeks
|
Serum neutralizing activity against a panel of HIV-1 isolates before and after 3BNC117-LS infusion.
|
48 weeks
|
HIV-specific T and B cell immune responses following 3BNC117-LS infusion
Time Frame: 48 weeks
|
HIV-specific T and B cell immune responses following 3BNC117-LS infusion
|
48 weeks
|
T cell counts after 3BNC117-LS infusion
Time Frame: 48 weeks
|
Absolute and relative CD4 + and CD8+ T cell counts after 3BNC117-LS infusion.
|
48 weeks
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
Other Study ID Numbers
- YCO-0946
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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