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

Phase 1

Completed

• Conditions: Healthy; HIV
• Interventions: Biological: 30 mg/kg, single dose IV administration of 10-1074; Biological: 10 mg/kg, single dose IV administration of 10-1074; Biological: 3 mg/kg, single dose IV administration of 10-1074

• Registration Number: NCT02511990
• Lead Sponsor: Rockefeller University

Brief Summary

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.

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 Timeline

• Study Start: 2015-07
• Study First Submitted: 2015-07-24
• Study First Submitted QC: 2015-07-28
• Study First Posted: 2015-07-30
• Primary Completion: 2016-12
• Study Completion: 2017-12
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-31
• Last Update Posted: 2018-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2C	30 mg/kg, single dose IV administration of 10-1074	HIV-uninfected individuals 30 mg/kg, single dose IV administration of 10-1074
Group 2D	30 mg/kg, single dose IV administration of 10-1074	HIV-uninfected individuals 30 mg/kg, single dose IV administration of 10-1074
Group 1D	30 mg/kg, single dose IV administration of 10-1074	HIV-infected individuals Off ART, HIV-1 viral load \< 100,000 copies/ml 30 mg/kg, single dose IV administration of 10-1074
Group 1B	10 mg/kg, single dose IV administration of 10-1074	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
Group 1A	3 mg/kg, single dose IV administration of 10-1074	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
Group 1C	30 mg/kg, single dose IV administration of 10-1074	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
Group 2A	3 mg/kg, single dose IV administration of 10-1074	HIV-uninfected individuals 3 mg/kg, single dose IV administration of 10-1074
Group 2B	10 mg/kg, single dose IV administration of 10-1074	HIV-uninfected individuals 10 mg/kg, single dose IV administration of 10-1074

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (2)

The Rockefeller University; 🇺🇸 New York, New York, United States

University of Cologne; 🇩🇪 Cologne, Germany