3BNC117 and 10-1074 in HIV Uninfected Adults
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| ClinicalTrials.gov Identifier: NCT02824536 |
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Recruitment Status :
Completed
First Posted : July 6, 2016
Last Update Posted : April 17, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Human Immunodeficiency Virus | Drug: 3BNC117 Drug: 10-1074 Drug: Placebo | Phase 1 |
The study will be conducted under a placebo-controlled, double blind, randomized allocation of the study products. Study participants in each study group will be randomized to receive intravenous infusions of 3BNC117 and 10-1074 or placebo. 3BNC117 and 10-1074 will be administered at 2 dose levels (3 mg/kg and 10 mg/kg). These doses were selected based on the planned development of subcutaneous formulations for the prophylactic use of these products. The study will consist of 3 groups. Enrollment in Group 1 will begin first and participants will be enrolled at least one day apart. Eight participants will be enrolled in each group; 6 will be randomized receive the study drugs and 2 will be randomized to receive placebo. Participants in Group 1 will receive a single infusion of each antibody at 10mg/kg at Week 0. Enrollment in Group 2 will begin only after Day 28 safety data from all participants in Group 1, including ophthalmologic exams, are available. Enrollment in Group 3 will begin only after the Day 28 safety data from all participants in Group 2 is available. If > 1 grade 3 or higher adverse events deemed probably or definitely related to the study drugs occurs in a single group, the next group will not be enrolled pending safety monitoring committee (SMC) review. Participants in Groups 2 and 3 will receive 3 infusions of each antibody at Weeks 0, 8, and 16, at a dose of either 3mg/kg or 10mg/kg. The antibodies will be administered sequentially via intravenous infusion. Each antibody will be administered over 60 minutes.
Following product infusions, study participants will return for safety assessments at multiple time points. Blood samples will be collected for safety testing at weeks 1, 2, and 4 following each infusion, then at multiple time points until the end of study follow up.
Baseline pharmacokinetic (PK) assessments will be performed before the start of the first infusion. Peak PK sampling for 3BNC117 will occur following the completion of the 3BNC117 infusion prior to the start of the 10-1074 infusion. Peak PK sampling for 10-1074 will occur following the completion of the 10-1074 infusion. Additional PK assessments will occur at multiple time points during study follow up. Study participants will be followed for a total of 24 weeks following the final antibody infusion.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 24 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Prevention |
| Official Title: | A Phase 1 Study of the Safety and Pharmacokinetics of the Combination of 3BNC117 and 10-1074 in HIV-uninfected Adults |
| Actual Study Start Date : | June 23, 2016 |
| Actual Primary Completion Date : | January 9, 2018 |
| Actual Study Completion Date : | January 9, 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Group 1
Participants will be randomized in a 3:1 ratio to receive one intravenous infusion of 3BNC117 and one intravenous infusion of 10-1074, each dosed at 10 mg/kg OR placebo (sterile saline), on day 0.
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Drug: 3BNC117
Intravenous Infusion of 3BNC117
Other Name: Monoclonal Antibody 3BNC117 Drug: 10-1074 Intravenous Infusion of 10-1074
Other Name: Monoclonal Antibody 10-1074 Drug: Placebo Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Other Name: Sterile Saline (NaCl 0.9%) |
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Experimental: Group 2
Participants will be randomized in a 3:1 ratio to receive three intravenous infusions of 3BNC117 and three intravenous infusions of 10-1074, each dosed at 3 mg/kg OR placebo (sterile saline), on day 0, week 8, and week 16.
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Drug: 3BNC117
Intravenous Infusion of 3BNC117
Other Name: Monoclonal Antibody 3BNC117 Drug: 10-1074 Intravenous Infusion of 10-1074
Other Name: Monoclonal Antibody 10-1074 Drug: Placebo Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Other Name: Sterile Saline (NaCl 0.9%) |
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Experimental: Group 3
Participants will be randomized in a 3:1 ratio to receive three intravenous infusions of 3BNC117 and three intravenous infusions of 10-1074, each dosed at 10 mg/kg OR placebo (sterile saline), on day 0, week 8, and week 16.
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Drug: 3BNC117
Intravenous Infusion of 3BNC117
Other Name: Monoclonal Antibody 3BNC117 Drug: 10-1074 Intravenous Infusion of 10-1074
Other Name: Monoclonal Antibody 10-1074 Drug: Placebo Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Other Name: Sterile Saline (NaCl 0.9%) |
- The number of participants who experience adverse events within 1 week after the combination of 3BNC117 and 10-1074 infusion in all study groups. [ Time Frame: 1 week following each combination of 3BNC117 and 10-1074 infusion ]Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.
- Number of participants with induced anti-3BNC117 and anti-10-1074 antibodies [ Time Frame: 8 weeks following each combination of 3BNC117 and 10-1074 infusion ]
- Level of induced anti-3BNC117 and anti-10-1074 antibodies [ Time Frame: 8 weeks following each combination of 3BNC117 and 10-1074 infusion ]
- The number of participants who experience adverse events that occur during study follow up after 3BNC117 and 10-1074 infusions in all study groups. [ Time Frame: 24-40 weeks ]Adverse events include signs, symptoms and laboratory abnormalities.
- Neutralization activity of serum from study participants against a panel of viruses as measured by the TZM.bl neutralization assay. [ Time Frame: 24-40 weeks ]
- Elimination half-life (t1/2) of 3BNC117 and 10-1074 [ Time Frame: 24-40 weeks ]
- Clearance (CL/F) of 3BNC117 and 10-1074 [ Time Frame: 24-40 weeks ]
- Volume of distribution (Vz/F) of 3BNC117 and 10-1074 [ Time Frame: 24-40 weeks ]
- Area under the plasma concentration versus time curve (AUC) of 3BNC117 and 10-1074 [ Time Frame: 24-40 weeks ]
- Decay Curve of of 3BNC117 and 10-1074 [ Time Frame: 24-40 weeks ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- 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) for the duration of the study.
Exclusion Criteria:
- 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.
- Chronic Hepatitis B or Hepatitis C infection.
- Laboratory abnormalities in the parameters listed:
- Absolute neutrophil count ≤ 2,000;
- Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male;
- Platelet count ≤ 125,000;
- Alanine Aminotransferase (ALT) ≥ 1.25 x ULN; Aspartate Aminotransferase (AST) ≥ 1.25 x ULN;
- Alkaline phosphatase ≥ 1.5 x ULN
- Total bilirubin > 1.0 x ULN;
- Creatinine ≥1.1 x ULN;
- Pregnancy or lactation.
- Any vaccination within 14 days prior to infusion
- Receipt of any experimental HIV vaccine in the past.
- History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
- Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02824536
| United States, New York | |
| The Rockefeller University | |
| New York, New York, United States, 10065 | |
| Principal Investigator: | Yehuda Cohen, MD | Rockefeller University |
| Responsible Party: | Rockefeller University |
| ClinicalTrials.gov Identifier: | NCT02824536 History of Changes |
| Other Study ID Numbers: |
YCO-0899 |
| First Posted: | July 6, 2016 Key Record Dates |
| Last Update Posted: | April 17, 2018 |
| Last Verified: | April 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
Keywords provided by Rockefeller University:
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3BNC117 10-1074 Broadly neutralizing antibody HIV Prevention |
Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome HIV Infections Immune System Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases |
Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Antibodies Immunoglobulins Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |