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

NCT04223804 | Completed Phase 1 FDA Drug

• 2 other identifiers: M19-9392019-004866-16
• Study Type: interventional
• Target: 41
• Locations: 4 countries
• Sites: 23

Brief Summary

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.

Conditions

Human Immunodeficiency Virus (HIV); HIV Infection; HIV-1

Keywords

Human Immunodeficiency Virus (HIV); HIV Infection; HIV-1; ABBV-181; Analytical Treatment Interruption; Budigalimab; Programmed cell death protein-1 (PD-1); Anti-PD-1 Antibody

Outcome Measures

Primary Outcomes (8)

• 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

Study Arms (5)

Stage 1: Arm A

PLACEBO COMPARATOR

Participants will receive placebo.

Drug: Placebo

Stage 1: Arm B

EXPERIMENTAL

Participants will receive ABBV-181 dose A.

Drug: ABBV-181

Stage 1: Arm C

EXPERIMENTAL

Participants will receive ABBV-181 dose B.

Drug: ABBV-181

Stage 2: Arm D

PLACEBO COMPARATOR

Participants will receive Placebo.

Drug: Placebo

Stage 2: Arm E

EXPERIMENTAL

Participants will receive ABBV-181 dose C.

Drug: ABBV-181

Interventions

ABBV-181 DRUG

Intravenous (IV) Infusion

Also known as: Budigalimab

Stage 1: Arm B; Stage 1: Arm C; Stage 2: Arm E

Placebo DRUG

Intravenous (IV) infusion

Stage 1: Arm A; Stage 2: Arm D

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (23)

Franco Felizarta, Md /Id# 215721

Bakersfield, California, 93301, United States

Location

Ruane Clinical Research Group /ID# 224866

Los Angeles, California, 90036, United States

Location

Quest Clinical Research /ID# 215796

San Francisco, California, 94115-3037, United States

Location

George Washington University Medical Faculty Associates /ID# 213893

Washington D.C., District of Columbia, 20037-3201, United States

Location

Midway Immunology and Research /ID# 215587

Ft. Pierce, Florida, 34982, United States

Location

University of Miami, Miller School of Medicine /ID# 213833

Miami, Florida, 33136, United States

Location

Orlando Immunology Center /ID# 243276

Orlando, Florida, 32803, United States

Location

Triple O Research Institute /ID# 224863

West Palm Beach, Florida, 33407-3100, United States

Location

Be Well Medical Center /ID# 223841

Berkley, Michigan, 48072-3046, United States

Location

Mayo Clinic - Rochester /ID# 217820

Rochester, Minnesota, 55905-0001, United States

Location

Saint Michael's Medical Center /ID# 228733

Newark, New Jersey, 07102, United States

Location

University of Cincinnati /ID# 215615

Cincinnati, Ohio, 45267-0585, United States

Location

Prism Health North Texas - Oak Cliff Health Center /ID# 214036

Dallas, Texas, 75208-4599, United States

Location

North TX Infectious Diseases /ID# 224861

Dallas, Texas, 75246, United States

Location

Peter Shalit, M.D. /ID# 224870

Seattle, Washington, 98104-3595, United States

Location

Holdsworth House Medical Practice /ID# 215352

Darlinghurst, New South Wales, 2010, Australia

Location

St Vincent's Hospital Sydney /ID# 215354

Darlinghurst, New South Wales, 2010, Australia

Location

The Royal Melbourne Hospital /ID# 215351

Parkville, Victoria, 3050, Australia

Location

Ottawa Hospital Research Institute /ID# 218083

Ottawa, Ontario, K1H 8L6, Canada

Location

Toronto General Hospital /ID# 218082

Toronto, Ontario, M5G 2C4, Canada

Location

McGill Univ Clinical Research /ID# 218081

Montreal, Quebec, H2X 2P4, Canada

Location

Clinical Research Puerto Rico /ID# 218821

San Juan, 00909, Puerto Rico

Location

Puerto Rico AIDS Clinical Trials Unit CRS /ID# 213761

San Juan, 00935, Puerto Rico

Location

Related Publications (1)

• Ramgopal MN, Lalezari JP, Pires Dos Santos AG, Krishnan P, Vaidya TR, Zhou F, Betman H, Dorr P, Mostafa NM, Alcaide ML, Felizarta F, Routy JP. Budigalimab, an anti-PD-1 inhibitor, for people living with HIV-1: a randomized, placebo-controlled phase 1b study. Nat Med. 2025 Nov;31(11):3879-3888. doi: 10.1038/s41591-025-03993-0. Epub 2025 Oct 15.

  PMID: 41094034 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

budigalimab

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: January 10, 2020
• Study Start: January 30, 2020
• Primary Completion: February 27, 2023
• Study Completion: February 27, 2023
• Last Updated: March 9, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); PR (2); AU (3); CA (3)