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A Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 10-1074

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of Cologne
Information provided by (Responsible Party):
Rockefeller University
ClinicalTrials.gov Identifier:
NCT02511990
First received: July 24, 2015
Last updated: December 23, 2016
Last verified: December 2016
  Purpose
This is a phase 1 clinical trial to evaluate the safety, pharmacokinetics and the antiretroviral effects of the highly neutralizing anti-HIV-1 monoclonal antibody 10-1074 in HIV-infected and HIV-uninfected individuals.

Condition Intervention Phase
Healthy
HIV
Biological: 3 mg/kg, single dose IV administration of 10-1074
Biological: 10 mg/kg, single dose IV administration of 10-1074
Biological: 30 mg/kg, single dose IV administration of 10-1074
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase 1, Open Label, Dose-escalation Study of the Safety, Pharmacokinetics and Antiretroviral Activity of 10-1074 Monoclonal Antibody in HIV-infected and HIV-uninfected Individuals

Resource links provided by NLM:


Further study details as provided by Rockefeller University:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 24 weeks after 10-1074 administration ]

Secondary Outcome Measures:
  • Serum peak concentration of 10-1074, measured in micrograms per ml [ Time Frame: 24 hours after 10-1074 administration ]
  • Serum half-life of 10-1074 expressed in days [ Time Frame: 24 Weeks after 10-1074 administration ]
  • Plasma HIV-1 RNA levels measured in copies/ml [ Time Frame: 2 weeks after 10-1074 administration ]

Enrollment: 33
Study Start Date: July 2015
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1A

HIV-infected individuals Off ART, HIV-1 viral load < 100,000 copies/ml or On ART, HIV-1 viral load < 500 copies/ml

3 mg/kg, single dose IV administration of 10-1074

Biological: 3 mg/kg, single dose IV administration of 10-1074
3 mg/kg, single dose IV administration of 10-1074
Experimental: Group 1B

HIV-infected individuals Off ART, HIV-1 viral load < 100,000 copies/ml or On ART, HIV-1 viral load < 500 copies/ml

10 mg/kg, single dose IV administration of 10-1074

Biological: 10 mg/kg, single dose IV administration of 10-1074
10 mg/kg, single dose IV administration of 10-1074
Experimental: Group 1C

HIV-infected individuals Off ART, HIV-1 viral load < 100,000 copies/ml or On ART, HIV-1 viral load < 500 copies/ml

30 mg/kg, single dose IV administration of 10-1074

Biological: 30 mg/kg, single dose IV administration of 10-1074
30 mg/kg, single dose IV administration of 10-1074
Experimental: Group 1D

HIV-infected individuals Off ART, HIV-1 viral load < 100,000 copies/ml

30 mg/kg, single dose IV administration of 10-1074

Biological: 30 mg/kg, single dose IV administration of 10-1074
30 mg/kg, single dose IV administration of 10-1074
Experimental: Group 2A

HIV-uninfected individuals

3 mg/kg, single dose IV administration of 10-1074

Biological: 3 mg/kg, single dose IV administration of 10-1074
3 mg/kg, single dose IV administration of 10-1074
Experimental: Group 2B

HIV-uninfected individuals

10 mg/kg, single dose IV administration of 10-1074

Biological: 10 mg/kg, single dose IV administration of 10-1074
10 mg/kg, single dose IV administration of 10-1074
Experimental: Group 2C

HIV-uninfected individuals

30 mg/kg, single dose IV administration of 10-1074

Biological: 30 mg/kg, single dose IV administration of 10-1074
30 mg/kg, single dose IV administration of 10-1074
Experimental: Group 2D

HIV-uninfected individuals

30 mg/kg, single dose IV administration of 10-1074

Biological: 30 mg/kg, single dose IV administration of 10-1074
30 mg/kg, single dose IV administration of 10-1074

Detailed Description:
In preclinical studies carried out in humanized mice and non-human primates, 10-1074 alone or in combination with other neutralizing antibodies led to protection from HIV or simian/human immunodeficiency virus (SHIV) infection and also to sustained suppression of HIV plasma viremia. The aims of this protocol are to evaluate the safety, tolerability and pharmacokinetics profile of 10-1074 in both HIV-infected and HIV-uninfected individuals, and its antiretroviral activity in HIV-infected individuals.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Group 1 (HIV-infected)

  • Males and females, age 18 to 65
  • HIV-1 infection confirmed by two independent assays.
  • Group (1A-1C): HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml by standard assays, or on ART with HIV-1 plasma RNA levels < 500 copies/ml. HIV-1 RNA levels should be measured on 2 occasions, at least 1 week apart and one measurement must be performed within 49 days prior to enrollment.
  • Group (1D): HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000 copies/ml by standard assays, measured on 2 occasions, at least 1 week apart. At least one measurement must be performed within 49 days prior to enrollment.
  • Current CD4 count > 300 cells/μl.
  • If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception from 10 days prior to the 10-1074 infusion until the end of the study.

Group 2 (HIV-uninfected):

  • 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 throughout the study period, as described for the HIV-infected groups above.

Exclusion Criteria:

Group 1 (HIV-infected):

  • Have a history of AIDS-defining illness within 1 year prior to enrollment.
  • 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.
  • Chronic Hepatitis B or Hepatitis C infection.
  • Laboratory abnormalities in the parameters listed below:

Absolute neutrophil count ≤ 1,000; Hemoglobin ≤10 gm/dL; Platelet count ≤100,000; ALT ≥ 2.0 x ULN; AST ≥ 2.0 x ULN; Total bilirubin ≥ 1.25 x ULN; Creatinine ≥ 1.1 x ULN; Coagulation parameters (PT, PTT or INR) ≥ 1.25 x ULN.

  • Pregnancy or lactation.
  • Any vaccination within 14 days prior to 10-1074 administration.
  • 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.

Group 2 (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 (such as autoimmune diseases) 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 infection.
  • Chronic Hepatitis B or Hepatitis C infection.
  • Laboratory abnormalities in the parameters listed:

Absolute neutrophil count ≤ 1,500; Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male; Platelet count ≤ 140,000; Alanine transaminase (ALT) ≥ 1.25 x upper limit of normal (ULN); aspartate transaminase (AST) ≥ 1.25 x ULN; Total bilirubin ≥ 1.25 x ULN; Creatinine ≥ 1.1 x ULN; Coagulation parameters (prothrombin time - PT, partial thromboplastin time - PTT or INR) ≥ 1.25 x ULN.

  • Pregnancy or lactation.
  • Any vaccination within 14 days prior to 10-1074 administration.
  • 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02511990

Locations
United States, New York
The Rockefeller University
New York, New York, United States, 10065
Germany
University of Cologne
Cologne, Germany, 50937
Sponsors and Collaborators
Rockefeller University
University of Cologne
Investigators
Principal Investigator: Marina Caskey, MD Rockefeller University
  More Information

Responsible Party: Rockefeller University
ClinicalTrials.gov Identifier: NCT02511990     History of Changes
Other Study ID Numbers: MCA-0885
Study First Received: July 24, 2015
Last Updated: December 23, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Rockefeller University:
HIV
10-1074
Monoclonal Antibody

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 30, 2017