10E8.4/iMab Bispecific Antibody in HIV-uninfected and HIV-infected Adults

NCT03875209 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AAAS1239
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

Many HIV-infected individuals mount a broad neutralizing serologic response 2-3 years after infection. Broadly neutralizing antibodies might play an important role in protection from acquisition of HIV infection because they can protect macaques from infection, and the presence of anti-HIV antibodies was the only positive correlate of protection in an HIV vaccine efficacy trial (RV144 trial). HIV neutralizing antibodies also have the potential to alter the course of HIV infection in humans. Therefore, these antibodies might be useful to both prevent and treat HIV-1 infection. This is a phase 1 dose escalating clinical trial to evaluate the safety, tolerability, pharmacokinetics and the antiretroviral effects of a novel bispecific monoclonal antibody 10E8.4/iMab in HIV-infected and HIV-uninfected individuals. The study will be conducted as a multi-center study at the Columbia University Medical Center in New York City and the Orlando Immunology Center in Orlando, Florida.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (4)

• Safety of the highest single intravenous dose of 10E8.4/iMab in HIV uninfected individuals. Safety of a single dose of intravenous dose of 10E8.4/iMab in HIV uninfected individuals

  Percentage of subjects experiencing a dose limiting toxicity defined as a Grade 3 or 4 adverse events as per the toxicity grading scale for healthy volunteers enrolled in preventative vaccine trials

  24 weeks

• Safety of the highest single intravenous dose of 10E8.4/iMab in HIV infected individuals Safety of a single dose of intravenous dose of 10E8.4/iMab in HIV uninfected individuals

  Percentage of subjects experiencing a dose limiting toxicity defined as a Grade 3 or more adverse event as per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events v 2.1

  24 weeks

• Injection site reactions associated with a single subcutaneous injection of 10 E8.4/iMab in HIV uninfected individuals

  Percentage of injections associated with a Grade 2 or greater injection site reaction as per the toxicity grading scale for healthy volunteers enrolled in preventative vaccine trials

  24 weeks

• Systemic infusion reaction associated with the intravenous administration of any dose of 10E8.4/iMab

  Percentage of subjects receiving intravenous 10E8.4/iMab as per CTCAE version 5.0.

  24 weeks

Secondary Outcomes (12)

• Antiviral activity of the highest single dose of 10E8.4/iMab given intravenously to viremic HIV infected individuals

  7 days

• Antiviral activity of the highest single dose of 10E8.4/iMab given intravenously to viremic HIV infected individuals

  14 days

• Antiviral activity of the highest single dose of 10E8.4/iMab given intravenously to viremic HIV infected individuals

  28 days

• Serum levels 10E8.4/iMab after the highest single dose of 10E8.4/iMab given intravenously to HIV infected and uninfected individuals

  7 days

• Serum levels of 10E8.4/iMab after the highest single dose of 10E8.4/iMab given intravenously to HIV infected and uninfected individuals

  14 days

Study Arms (4)

Arm 1: 10E8.4/iMab IV or SC HIV-

EXPERIMENTAL

Arm 1; Groups A-C; 3 dosing groups: HIV-uninfected individuals

Biological: 10E8.4/iMab

Arm 2: 10E8.4/iMab IV HIV-

EXPERIMENTAL

Arm 2; Groups D-F; 3 dosing groups: HIV-uninfected individuals

Biological: 10E8.4/iMab

Arm 3 and 3a: 10E8.4/iMab IV HIV+

EXPERIMENTAL

Arm 3; Group H; 1 dosing group: HIV-infected individuals with HIV-1 RNA levels between 1,000 and 100,000 copies/mL and cluster of differentiation 4 (CD4)\>350 cells/mm3; Arm 3a; Group I; 1 dosing group: HIV-infected and suppressed individuals

Biological: 10E8.4/iMab

Arm 4: 10E8.4/iMab SC HIV-

EXPERIMENTAL

Arm 4; Groups J and K: HIV-uninfected individuals

Biological: 10E8.4/iMab

Interventions

10E8.4/iMab BIOLOGICAL

bispecific monoclonal antibody

Arm 1: 10E8.4/iMab IV or SC HIV-; Arm 2: 10E8.4/iMab IV HIV-; Arm 3 and 3a: 10E8.4/iMab IV HIV+; Arm 4: 10E8.4/iMab SC HIV-

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers born male and female as assessed by medical history and physical examination
• Aged \>18 and \<60 years at the time of screening
• Ability and willingness to provide written informed consent
• Willingness to comply with protocol schedule
• Willingness to undergo HIV-1 testing
• Non-reactive 4th generation point of care HIV-1 test at screening
• Hepatitis B Surface antigen negative
• Hepatitis C antibody negative, or if reactive, Hepatitis C RNA undetectable in plasma
• Volunteers born female of reproductive potential, sexually active with a male sex partner must agree to use one effective method of contraception from the time of signing the consent to completion of the study and agree to pregnancy testing as per the schedule of events.
• Study participants born female with reproductive potential are defined as pre-menopausal volunteers born female who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Volunteers born female are considered menopausal if they have not had a menses for at least 12 months and have an follicle stimulating hormone (FSH) of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.
• Aged \>18 and \<60 years at the time of screening
• Ability and willingness to provide written informed consent
• Willingness to comply with protocol schedule
• Willingness to undergo HIV-1 testing
• Reactive 4th generation point of care HIV-1 test at screening

You may not qualify if:

• Confirmed HIV-1 infection
• At high risk of HIV-1 infection as defined by:
• Unprotected intercourse with a casual or HIV-infected partner over the past 12 months
• In a serodisconcordant relationship with an HIV-1 infected partner
• A diagnosed new sexually transmitted infection within the past 12 months
• Exchange of money or drugs for sex in the last 12 months
• More than 2 sexual partners, defined as insertive or receptive vaginal or anal intercourse, within the past 6 months
• Weight above 100 kg at screening. Note that subjects above 80 kg may not be randomized into the SC dosing group in Arm 4.
• Any acute or chronic medical condition that in the opinion of the investigator would preclude participation
• Immunodeficiency or chronic autoimmune disease
• Intravenous drug use
• Excessive use of alcohol or recreational drugs that in the opinion of the investigator would preclude participation.
• Decompensated psychiatric illness
• Need for chronic immunotherapy including systemic corticosteroids, other monoclonal antibody therapy, or immunosuppressive drugs
• If born female, pregnant, lactating or planning on becoming pregnant over the study period

Sponsors & Collaborators

• David Ho: lead
• Bill and Melinda Gates Foundation: collaborator
• International AIDS Vaccine Initiative: collaborator
• The Emmes Company, LLC: collaborator

Study Sites (2)

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Columbia University Research Unit

New York, New York, 10032, United States

Location

Related Publications (2)

• Hraber P, Seaman MS, Bailer RT, Mascola JR, Montefiori DC, Korber BT. Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS. 2014 Jan 14;28(2):163-9. doi: 10.1097/QAD.0000000000000106.

  PMID: 24361678 BACKGROUND

• Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, Evans DT, Montefiori DC, Karnasuta C, Sutthent R, Liao HX, DeVico AL, Lewis GK, Williams C, Pinter A, Fong Y, Janes H, DeCamp A, Huang Y, Rao M, Billings E, Karasavvas N, Robb ML, Ngauy V, de Souza MS, Paris R, Ferrari G, Bailer RT, Soderberg KA, Andrews C, Berman PW, Frahm N, De Rosa SC, Alpert MD, Yates NL, Shen X, Koup RA, Pitisuttithum P, Kaewkungwal J, Nitayaphan S, Rerks-Ngarm S, Michael NL, Kim JH. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012 Apr 5;366(14):1275-86. doi: 10.1056/NEJMoa1113425.

  PMID: 22475592 BACKGROUND

Study Officials

• David D. Ho, MD

  ADARC at CUIMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants in SC dosing Arm 4 Groups J and K will be blinded as will providers and members of the study site team. Study pharmacists will not be blinded. Safety monitoring committee will not be blinded. All participants treated IV and participants treated 1 mg/kg SC will not be masked (open-label).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Dose escalation, open-label (IV or SC administration), placebo-controlled (SC administration)

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: March 14, 2019
• Study Start: April 8, 2019
• Primary Completion: March 23, 2022
• Study Completion: March 23, 2022
• Last Updated: March 7, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)