Clinical trial NCT02018510: A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 3BNC117
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
HIV
Keywords: Healthy Volunteers
HIV
Lead sponsor: Rockefeller University
Sponsor class: OTHER
Collaborators: name: Weill Medical College of Cornell University
name: Brigham and Women's Hospital
name: University of Cologne
First posted: 2013-12-23
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability
timeFrame: 24 weeks
Secondary outcomes:
measure: Pharmacokinetic profile
timeFrame: 24 hours post infusion
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: New York
country: United States
facility: The Rockefeller University
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Cologne
country: Germany
facility: University of Cologne
Study officials:
affiliation: Rockefeller Univesrity
name: Marina Caskey, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.