A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117
1 other identifier
interventional
49
2 countries
4
Brief Summary
The proposed study is a first-in-man phase I study that aims to evaluate the safety, tolerability and pharmacokinetics of 3BNC117 in HIV-infected and HIV-uninfected subjects, and its antiretroviral activity in HIV-infected subjects.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 healthy
Started Jan 2014
Longer than P75 for phase_1 healthy
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 17, 2013
CompletedFirst Posted
Study publicly available on registry
December 23, 2013
CompletedStudy Start
First participant enrolled
January 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2016
CompletedDecember 26, 2016
December 1, 2016
2 years
December 17, 2013
December 23, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Safety and tolerability
To evaluate the safety and tolerability profile of one or two intravenous infusions of 3BNC117 at 3 increasing dose levels in HIV-infected and HIV-uninfected individuals.
24 weeks
Secondary Outcomes (1)
Pharmacokinetic profile
24 hours post infusion
Study Arms (15)
Group 1A
EXPERIMENTALHIV-uninfected individuals 1 mg/kg, single dose IV administration of 3BNC117
Groups 1B
EXPERIMENTALHIV-uninfected individuals 3 mg/kg, single dose IV administration of 3BNC117
Group 1C
EXPERIMENTALHIV-uninfected individuals 10 mg/kg, single dose IV administration of 3BNC117
Group 1D
EXPERIMENTALHIV-uninfected individuals 10 mg/kg, two doses IV of 3BNC117
Group 1E
EXPERIMENTALHIV-uninfected individuals 30 mg/kg, single dose IV administration of 3BNC117
Group 1F
EXPERIMENTALHIV-uninfected individuals 30 mg/kg, two doses IV of 3BNC117
Group 2A
EXPERIMENTALHIV-infected individuals on or off ART 1 mg/kg, single dose IV administration of 3BNC117
Group 2B
EXPERIMENTALHIV-infected individuals on or off ART 3 mg/kg, single dose IV administration of 3BNC117
Group 2C
EXPERIMENTALHIV-infected individuals on or off ART 10 mg/kg, single dose IV administration of 3BNC117
Group 2D
EXPERIMENTALHIV-infected individuals on or off ART 30 mg/kg, single dose IV administration of 3BNC117
Group 2E
EXPERIMENTALHIV-infected individuals off ART, VL 2,000-100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
Group 3
EXPERIMENTALHIV-infected individuals off ART, VL \< 2,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
Group 4
EXPERIMENTALHIV-infected individuals on ART, VL \< 100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
Group 5A
EXPERIMENTALHIV-infected individuals on ART, VL \< 20 copies/ml 10 mg/kg, single dose IV administration of 3BNC117
Group 5B
EXPERIMENTALHIV-infected individuals on ART, VL \< 20 copies/ml 30 mg/kg, single dose IV administration of 3BNC117
Interventions
1 mg/kg, single dose IV administration of 3BNC117
3 mg/kg, single dose IV administration of 3BNC117
10 mg/kg, single dose IV administration of 3BNC117
30 mg/kg, single dose IV administration of 3BNC117
10 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12
30 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12
Eligibility Criteria
You may qualify if:
- Group 1 (HIV-uninfected):
- Adult males and females, age 18 to 65
- Amenable to HIV risk reduction counseling and agrees to maintaining behavior consistent with low risk of HIV exposure;
- If a sexually active male or female, participating in sexual activity that could lead to pregnancy, agrees to use an effective method of contraception throughout the study.
- Groups 2-5 (HIV-infected):
- Age 18 to 65
- HIV infection confirmed by ELISA and immunoblot
- Groups 2A-D - on ART with HIV-1 plasma RNA levels below 100,000 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA level between 2,000-100,000 copies/ml by standard assays on 2 occasions at least 1 week apart;
- Group 2E - Untreated HIV-infected (not on ART for at least 8 weeks): HIV-1 RNA plasma levels between 2,000 - 100,000 copies/ml;
- Group 3 - Untreated HIV controllers (not on ART for at least 8 weeks): HIV-1 RNA plasma level of \< 2,000 copies/ml by standard assays, on 2 occasions, at least 1 week apart, and ART-naive.
- Group 4 - ART treated with HIV-1 RNA plasma level of \> 20 copies/ml by standard assays on 2 occasions, at least 1 week apart, while on combination antiretroviral therapy;
- Groups 5A and 5B - ART treated with HIV-1 RNA plasma level of \< 20 copies/ml by standard assays on 2 occasions, at least 1 week apart, while on combination antiretroviral therapy;
- Current CD4 cell count \> 300 cells/µl
- If sexually active male and female, participating in sexual activity that could lead to pregnancy, agrees to use an effective method of contraception throughout the study.
You may not qualify if:
- Group 1 (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 that in the opinion of the investigator would preclude participation;
- Within the 12 months prior to enrollment, the volunteer has a history of sexually transmitted disease;
- Hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies);
- Laboratory abnormalities in the parameters listed below:
- Absolute neutrophil count ≤ 2,000
- Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male
- Platelet count ≤ 140,000
- ALT ≥ 1.25 x ULN
- AST ≥ 1.25 x ULN
- Total bilirubin ≥ 1.1 ULN
- Creatinine ≥ 1.1 x ULN
- Coagulation parameters (PT, PTT, INR) ≥ 1.1 x ULN
- +23 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Rockefeller Universitylead
- Weill Medical College of Cornell Universitycollaborator
- Brigham and Women's Hospitalcollaborator
- University of Colognecollaborator
Study Sites (4)
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
The Rockefeller University
New York, New York, 10065, United States
Weill Cornell Medical Center
New York, New York, 10065, United States
University of Cologne
Cologne, 50937, Germany
Related Publications (1)
Schoofs T, Klein F, Braunschweig M, Kreider EF, Feldmann A, Nogueira L, Oliveira T, Lorenzi JC, Parrish EH, Learn GH, West AP Jr, Bjorkman PJ, Schlesinger SJ, Seaman MS, Czartoski J, McElrath MJ, Pfeifer N, Hahn BH, Caskey M, Nussenzweig MC. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science. 2016 May 20;352(6288):997-1001. doi: 10.1126/science.aaf0972. Epub 2016 May 5.
PMID: 27199429DERIVED
Study Officials
- PRINCIPAL INVESTIGATOR
Marina Caskey, MD
Rockefeller Univesrity
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 17, 2013
First Posted
December 23, 2013
Study Start
January 1, 2014
Primary Completion
January 1, 2016
Study Completion
January 1, 2016
Last Updated
December 26, 2016
Record last verified: 2016-12
Data Sharing
- IPD Sharing
- Will not share