First-in-human Study of 10-1074-LS Alone and in Combination With 3BNC117-LS

• Status: Completed
• Trial end date: 2021-02-04
• Target enrollment: 0
• Participant gender: All

Summary

This first clinical study of 10-1074-LS will evaluate its safety, tolerability and pharmacokinetics profile when administered alone or in combination with 3BNC117-LS to HIV (human immunodeficiency virus) -infected and HIV-uninfected individuals.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Rockefeller University
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Immunoglobulins

Criteria

Inclusion Criteria:

Groups 1A-1B, 2A-2C, 4A-4B, 5, 7, 8, 9 (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 (i.e.

condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and nine months after 10-1074-LS and/or 3BNC117-LS administration.

• Female study participants of reproductive potential are defined as pre-menopausal women who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.

Groups 3B-3C, 6 (HIV-infected):

• Males and females, age 18 to 65.

• Confirmed HIV-1 infection.

• HIV-infected individuals on ART with HIV-1 plasma RNA levels < 50 copies/mL.

• Current CD4+ T cell count > 300 cells/μl.

• If sexually active male or female, and participating in sexual activity that could lead to pregnancy or transmission of HIV, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and nine months after 10-1074-LS and/or 3BNC117-LS administration.

Exclusion Criteria:

Groups 1A-1B, 2A-2C, 4A-4B, 5, 7, 8, 9 (HIV-uninfected):

• Confirmed HIV-1 or HIV-2 infection.

• Weight > 110 kg (subcutaneous groups only: 1A-1B, 4A-4B).

• History of immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant

• 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 participant has a history of sexually transmitted infection.

• Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.

• Laboratory abnormalities in the parameters listed:

• Absolute neutrophil count ≤ 1,500 cells/μL;

• Hemoglobin ≤ 11 gm/dL if female; ≤ 12.5 gm/dL if male;

• Platelet count ≤ 125,000 cells/μL;

• ALT ≥ 1.25 x ULN;

• AST ≥ 1.25 x ULN;

• Alkaline phosphatase ≥ 1.5 x ULN;by the trial physician within the last 6 months.

• Pregnancy or lactation.

• Any vaccination within 14 days prior to mAb infusions.

• Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.

• History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.

• Individuals with known hypersensitivity to any constituent of the investigational products.

• Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.

Groups 3B-3C, 6 (HIV-infected):

• Have a history of AIDS-defining illness within 3 years 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 (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.

• Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.

• Laboratory abnormalities in the parameters listed below:

• Absolute neutrophil count ≤ 1,000 cells/μl;

• Hemoglobin ≤ 10 gm/dL;

• Platelet count ≤ 100,000 cells/μl;

• ALT ≥ 1.5 x ULN;

• AST ≥ 1.5 x ULN;

• Alkaline phosphatase ≥ 1.5 x ULN;

• Total bilirubin > 1 x ULN;

• eGFR < 60 mL/min/1.73m2.

• Pregnancy or lactation.

• Any vaccination within 14 days prior to MAb infusions.

• Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.

• History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.

• Individuals with known hypersensitivity to any constituent of the investigational products.

• Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.