Overview

This trial is active, not recruiting.

Conditions healthy, hiv
Treatments 3 mg/kg, single dose iv administration of 10-1074, 10 mg/kg, single dose iv administration of 10-1074, 30 mg/kg, single dose iv administration of 10-1074
Phase phase 1
Sponsor Rockefeller University
Collaborator University of Cologne
Start date July 2015
End date July 2017
Trial size 51 participants
Trial identifier NCT02511990, MCA-0885

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose prevention
Arm
(Experimental)
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
3 mg/kg, single dose iv administration of 10-1074
3 mg/kg, single dose IV administration of 10-1074
(Experimental)
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
10 mg/kg, single dose iv administration of 10-1074
10 mg/kg, single dose IV administration of 10-1074
(Experimental)
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
30 mg/kg, single dose iv administration of 10-1074
30 mg/kg, single dose IV administration of 10-1074
(Experimental)
HIV-infected individuals Off ART, HIV-1 viral load < 100,000 copies/ml 30 mg/kg, single dose IV administration of 10-1074
30 mg/kg, single dose iv administration of 10-1074
30 mg/kg, single dose IV administration of 10-1074
(Experimental)
HIV-uninfected individuals 3 mg/kg, single dose IV administration of 10-1074
3 mg/kg, single dose iv administration of 10-1074
3 mg/kg, single dose IV administration of 10-1074
(Experimental)
HIV-uninfected individuals 10 mg/kg, single dose IV administration of 10-1074
10 mg/kg, single dose iv administration of 10-1074
10 mg/kg, single dose IV administration of 10-1074
(Experimental)
HIV-uninfected individuals 30 mg/kg, single dose IV administration of 10-1074
30 mg/kg, single dose iv administration of 10-1074
30 mg/kg, single dose IV administration of 10-1074
(Experimental)
HIV-uninfected individuals 30 mg/kg, single dose IV administration of 10-1074
30 mg/kg, single dose iv administration of 10-1074
30 mg/kg, single dose IV administration of 10-1074

Primary Outcomes

Measure
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: 24 weeks after 10-1074 administration

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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.

Additional Information

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
Principal investigator Marina Caskey, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Rockefeller University.