A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of ABBV-181 (Budigalimab) in Adult Participants With Human Immunodeficiency Virus (HIV)-1

A Randomized, Double-blind, Placebo-controlled, Phase 1b Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of ABBV-181 in HIV-1 Infected Adults

This study will be conducted in two stages and will test the safety/tolerability, pharmacokinetics (how the body handles study drug) and pharmacodynamics (effects on the immune system and the virus) of the study drug ABBV-181 in Human immunodeficiency virus (HIV)-1 infected participants undergoing Antiretroviral therapy (ART) interruption.

Study Overview

• Status: Completed
• Conditions: HIV Infection; HIV-1; Human Immunodeficiency Virus (HIV)
• Intervention / Treatment: Drug: Placebo; Drug: ABBV-181

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice /ID# 215352
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney /ID# 215354
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital /ID# 215351
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute /ID# 218083
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital /ID# 218082
  • Quebec
    • Montreal, Quebec, Canada, H2X 2P4
      • McGill Univ Clinical Research /ID# 218081
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico /ID# 218821
  • San Juan, Puerto Rico, 00935
    • Puerto Rico AIDS Clinical Trials Unit CRS /ID# 213761
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Franco Felizarta, Md /Id# 215721
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group /ID# 224866
    • San Francisco, California, United States, 94115-3037
      • Quest Clinical Research /ID# 215796
  • District of Columbia
    • Washington, District of Columbia, United States, 20037-3201
      • George Washington University Medical Faculty Associates /ID# 213893
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research /ID# 215587
    • Miami, Florida, United States, 33136
      • University of Miami, Miller School of Medicine /ID# 213833
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center /ID# 243276
    • West Palm Beach, Florida, United States, 33407-3100
      • Triple O Research Institute /ID# 224863
  • Michigan
    • Berkley, Michigan, United States, 48072-3046
      • Be Well Medical Center /ID# 223841
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic - Rochester /ID# 217820
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center /ID# 228733
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0585
      • University of Cincinnati /ID# 215615
  • Texas
    • Dallas, Texas, United States, 75208-4599
      • Prism Health North Texas - Oak Cliff Health Center /ID# 214036
    • Dallas, Texas, United States, 75246
      • North TX Infectious Diseases /ID# 224861
  • Washington
    • Seattle, Washington, United States, 98104-3595
      • Peter Shalit, M.D. /ID# 224870

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:

• Body Mass Index (BMI) between 18.0 and 35 kg/m2.
• HIV-1 infected on antiretroviral therapy (ART) for at least 12 months prior to screening and on current ART regimen for at least 8 weeks prior to screening.

• Meets HIV-specific laboratory parameters as below:

  • Plasma HIV-1 RNA below lower limit of quantification (LLOQ) at screening and at least 6 months prior to screening.
  • CD4+ T cell count >= 500 cells/uL at screening and at least once during the 12 months prior to screening.
  • CD4+ T cell nadir of >= 200 cells/uL during chronic infection.
• Willing to undergo ART interruption.
• Agrees to use an effective barrier method of protection (male and/or female condoms) during sexual activity for protection against HIV-1 transmission throughout the entire study.

Exclusion Criteria:

• Known resistance to at least 2 classes of ART.
• History of AIDS-defining illness.
• Active or suspected malignancy or history of malignancy (other than basal cell skin cancer or cervical carcinoma in situ) in the past 5 years.
• History of or active immunodeficiency (other than HIV).
• Active autoimmune disease or history of autoimmune disease that has required systemic treatment.
• Prior receipt of immunomodulatory or immunosuppressive (including intravenous infusion or oral steroids at any dose, but excluding steroids that are inhaled, topical or by local injection) therapy within 24 weeks prior to the first dose of study drug.
• Prior therapy/exposure to ABBV-181 or any other immune checkpoint inhibitor.
• Current hepatitis B virus or hepatitis C virus infection.
• Clinically significant medical disorders that might expose the participants to undue risk of harm, confound study outcomes, or prevent the participant from completing the study (including but not limited to significant or unstable cardiac, neurologic or pulmonary disease, chronic active infectious disease except for HIV, chronic liver disease, poorly controlled diabetes mellitus and history of Stevens Johnson Syndrome toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS)).
• Known psychiatric or substance abuse disorders that would interfere with adherence to study requirements.
• Female participants must not be pregnant, breastfeeding, or considering becoming pregnant during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Stage 1: Arm A; Participants will receive placebo.	Drug: Placebo; Intravenous (IV) infusion
Experimental: Stage 1: Arm B; Participants will receive ABBV-181 dose A.	Drug: ABBV-181; Intravenous (IV) Infusion; Other Names: Budigalimab
Experimental: Stage 1: Arm C; Participants will receive ABBV-181 dose B.	Drug: ABBV-181; Intravenous (IV) Infusion; Other Names: Budigalimab
Placebo Comparator: Stage 2: Arm D; Participants will receive Placebo.	Drug: Placebo; Intravenous (IV) infusion
Experimental: Stage 2: Arm E; Participants will receive ABBV-181 dose C.	Drug: ABBV-181; Intravenous (IV) Infusion; Other Names: Budigalimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Study Drug-Related Adverse Events Grade 3 or Higher	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of the study drug as either having a reasonable possibility or no reasonable possibility. AEs are given a grade from 1-5 with Grade 3 being severe but not life-threatening and requiring hospitalization, Grade 4 being life-threatening requiring immediate intervention and Grade 5 being death related to an AE.	Up to approximately 44 weeks
Number of Participants with Study Drug-Related Immune-Related Adverse Events (IRAE)	Assessed using the American Society of Clinical Oncology (ASCO) IRAE management guidelines (which utilizes the NIH CTCAE grading scale) but modified, as applicable, according to the NIH Division of AIDS (DAIDS) (v2.1) AE grading scale.	Up to approximately 44 weeks
Number of Participants with Adverse Events (AEs) Corresponding to Retroviral Rebound Syndrome	Adverse Events (AEs) Corresponding to Retroviral Rebound Syndrome.	Up to approximately 44 weeks
Maximum Observed Concentration (Cmax)	Maximum Observed Concentration (Cmax) of ABBV-181.	Up to approximately 36 weeks
Time to Cmax (Tmax)	Time to Cmax (Tmax) of ABBV-181.	Up to approximately 36 weeks
Observed Concentration (Ctrough)	Observed Concentration (Ctrough) at the end of the dosing intervals for ABBV-181.	Up to approximately 36 weeks
Area Under the Curve (AUCtau)	Area Under the Curve (AUCtau) during the dosing intervals for ABBV-181.	Up to approximately 36 weeks
Half-life (t1/2)	Half-life (t1/2) of ABBV-181 following the last dose.	Up to approximately 36 weeks

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2020
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): February 27, 2023

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 10, 2020

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: HIV-1; HIV Infection; Human Immunodeficiency Virus (HIV); ABBV-181; Anti-PD-1 Antibody; Analytical Treatment Interruption; Budigalimab; Programmed cell death protein-1 (PD-1)
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
• Other Study ID Numbers: M19-939; 2019-004866-16 (EudraCT Number)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes