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

NCT ID: NCT02018510

Last Updated: 2016-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2016-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy HIV

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Healthy Volunteers HIV

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Group 1A

HIV-uninfected individuals

1 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

1 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

1 mg/kg, single dose IV administration of 3BNC117

Groups 1B

HIV-uninfected individuals 3 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

3 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

3 mg/kg, single dose IV administration of 3BNC117

Group 1C

HIV-uninfected individuals 10 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

10 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

10 mg/kg, single dose IV administration of 3BNC117

Group 1D

HIV-uninfected individuals 10 mg/kg, two doses IV of 3BNC117

Group Type EXPERIMENTAL

10 mg/kg, two doses IV of 3BNC117

Intervention Type BIOLOGICAL

10 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12

Group 1E

HIV-uninfected individuals 30 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

30 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

30 mg/kg, single dose IV administration of 3BNC117

Group 1F

HIV-uninfected individuals 30 mg/kg, two doses IV of 3BNC117

Group Type EXPERIMENTAL

30 mg/kg, two doses IV of 3BNC117

Intervention Type BIOLOGICAL

30 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12

Group 2A

HIV-infected individuals on or off ART

1 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

1 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

1 mg/kg, single dose IV administration of 3BNC117

Group 2B

HIV-infected individuals on or off ART 3 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

3 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

3 mg/kg, single dose IV administration of 3BNC117

Group 2C

HIV-infected individuals on or off ART 10 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

10 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

10 mg/kg, single dose IV administration of 3BNC117

Group 2D

HIV-infected individuals on or off ART 30 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

30 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

30 mg/kg, single dose IV administration of 3BNC117

Group 2E

HIV-infected individuals off ART, VL 2,000-100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

30 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

30 mg/kg, single dose IV administration of 3BNC117

Group 3

HIV-infected individuals off ART, VL \< 2,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

30 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

30 mg/kg, single dose IV administration of 3BNC117

Group 4

HIV-infected individuals on ART, VL \< 100,000 copies/ml 30 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

30 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

30 mg/kg, single dose IV administration of 3BNC117

Group 5A

HIV-infected individuals on ART, VL \< 20 copies/ml 10 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

10 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

10 mg/kg, single dose IV administration of 3BNC117

Group 5B

HIV-infected individuals on ART, VL \< 20 copies/ml 30 mg/kg, single dose IV administration of 3BNC117

Group Type EXPERIMENTAL

30 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

30 mg/kg, single dose IV administration of 3BNC117

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

1 mg/kg, single dose IV administration of 3BNC117

1 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

3 mg/kg, single dose IV administration of 3BNC117

3 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

10 mg/kg, single dose IV administration of 3BNC117

10 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

30 mg/kg, single dose IV administration of 3BNC117

30 mg/kg, single dose IV administration of 3BNC117

Intervention Type BIOLOGICAL

10 mg/kg, two doses IV of 3BNC117

10 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12

Intervention Type BIOLOGICAL

30 mg/kg, two doses IV of 3BNC117

30 mg/kg, two IV administrations of 3BNC117 at weeks 0 and 12

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Weill Medical College of Cornell University

OTHER

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role collaborator

University of Cologne

OTHER

Sponsor Role collaborator

Rockefeller University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Marina Caskey, MD

Role: PRINCIPAL_INVESTIGATOR

Rockefeller Univesrity

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

The Rockefeller University

New York, New York, United States

Site Status

Weill Cornell Medical Center

New York, New York, United States

Site Status

University of Cologne

Cologne, , Germany

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Germany

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 27199429 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

MCA-0835

Identifier Type: -

Identifier Source: org_study_id