A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117

Healthy Clinical Trial

Official title:

A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117 Monoclonal Antibody in HIV-infected and HIV-uninfected Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02018510
• Other study ID #: MCA-0835
• Status: Completed
• Phase: Phase 1
• First received: December 17, 2013
• Last updated: December 23, 2016
• Start date: January 2014
• Est. completion date: January 2016

Study information

• Verified date: December 2016
• Source: Rockefeller University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

In preclinical studies carried out in humanized mice and non-human primates, 3BNC117 alone or in combination with other neutralizing antibodies led to protection from HIV-1 or SHIV infection and also to sustained suppression of HIV-1 plasma viremia. The aims of this protocol are to evaluate the safety, tolerability and pharmacokinetics profile of 3BNC117 in both HIV-infected and HIV-uninfected subjects,and its antiretroviral activity in HIV-infected subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion criteria:

• 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

• Pregnancy or breastfeeding;

• Any vaccination within 14 days prior to 3BNC117 administration;

• Receipt of any experimental HIV vaccine in the past or monoclonal antibody therapy of any kind in the past;

• Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.

• Groups 2-5 (HIV-infected):

• History of AIDS-defining illness

• 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, other than HIV infection, that in the opinion of the investigator would preclude participation;

• Hepatitis B (surface antigen, HbsAg) or hepatitis C (HCV antibodies);

• Laboratory abnormalities in the parameters listed below:

• Absolute neutrophil count = 1,300

• Hemoglobin = 10 gm/dL

• Platelet count = 125,000

• ALT = 2.0 x ULN

• AST = 2.0 x ULN

• Total bilirubin = 1.1 ULN

• Creatinine = 1.1 x ULN

• Coagulation parameters = 1.1 x ULN;

• Current antiretroviral regimen includes either maraviroc or enfuvirtide;

• Pregnancy or breastfeeding;

• Any vaccination within 14 days prior to 3BNC117 administration;

• Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past;

• Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Healthy
• HIV

Intervention

Biological:
• 1 mg/kg, single dose IV administration of 3BNC117
1 mg/kg, single dose IV administration of 3BNC117
• 3 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
10 mg/kg, single dose IV administration of 3BNC117
• 30 mg/kg, single dose IV administration of 3BNC117
30 mg/kg, single dose IV administration of 3BNC117
• 10 mg/kg, two doses IV of 3BNC117
10 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12
• 30 mg/kg, two doses IV of 3BNC117
30 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12

Locations

Country	Name	City	State
Germany	University of Cologne	Cologne
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	The Rockefeller University	New York	New York
United States	Weill Cornell Medical Center	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Rockefeller University	Brigham and Women's Hospital, University of Cologne, Weill Medical College of Cornell University

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Pharmacokinetic profile	To determine the pharmacokinetic profile of one or two intravenous infusions of 3BNC117 in HIV-uninfected and HIV-infected subjects.	24 hours post infusion	No