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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy; HIV
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Cologne, Germany, 50937
    • University of Cologne
• United States
  • New York
    • New York, New York, United States, 10065
      • The Rockefeller University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	24 weeks after 10-1074 administration

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rockefeller University
• Collaborators: University of Cologne

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: July 24, 2015
• First Submitted That Met QC Criteria: July 28, 2015
• First Posted (Estimate): July 30, 2015

Study Record Updates

• Last Update Posted (Actual): February 5, 2018
• Last Update Submitted That Met QC Criteria: January 31, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: HIV; Monoclonal Antibody; 10-1074
• Other Study ID Numbers: MCA-0885

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No