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

HIV Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04223804
• Other study ID #: M19-939
• Secondary ID: 2019-004866-16
• Status: Completed
• Phase: Phase 1
• Start date: January 30, 2020
• Est. completion date: February 27, 2023

Study information

• Verified date: March 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: February 27, 2023
• Est. primary completion date: February 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infection
• HIV Infections
• HIV-1
• Human Immunodeficiency Virus (HIV)
• Immunologic Deficiency Syndromes

Intervention

Drug:
• ABBV-181
Intravenous (IV) Infusion
• Placebo
Intravenous (IV) infusion

Locations

Country	Name	City	State
Australia	Holdsworth House Medical Practice /ID# 215352	Darlinghurst	New South Wales
Australia	St Vincent's Hospital Sydney /ID# 215354	Darlinghurst	New South Wales
Australia	The Royal Melbourne Hospital /ID# 215351	Parkville	Victoria
Canada	McGill Univ Clinical Research /ID# 218081	Montreal	Quebec
Canada	Ottawa Hospital Research Institute /ID# 218083	Ottawa	Ontario
Canada	Toronto General Hospital /ID# 218082	Toronto	Ontario
Puerto Rico	Clinical Research Puerto Rico /ID# 218821	San Juan
Puerto Rico	Puerto Rico AIDS Clinical Trials Unit CRS /ID# 213761	San Juan
United States	Franco Felizarta, Md /Id# 215721	Bakersfield	California
United States	Be Well Medical Center /ID# 223841	Berkley	Michigan
United States	University of Cincinnati /ID# 215615	Cincinnati	Ohio
United States	North TX Infectious Diseases /ID# 224861	Dallas	Texas
United States	Prism Health North Texas - Oak Cliff Health Center /ID# 214036	Dallas	Texas
United States	Midway Immunology and Research /ID# 215587	Fort Pierce	Florida
United States	Ruane Clinical Research Group /ID# 224866	Los Angeles	California
United States	University of Miami, Miller School of Medicine /ID# 213833	Miami	Florida
United States	Saint Michael's Medical Center /ID# 228733	Newark	New Jersey
United States	Orlando Immunology Center /ID# 243276	Orlando	Florida
United States	Mayo Clinic - Rochester /ID# 217820	Rochester	Minnesota
United States	Quest Clinical Research /ID# 215796	San Francisco	California
United States	Peter Shalit, M.D. /ID# 224870	Seattle	Washington
United States	George Washington University Medical Faculty Associates /ID# 213893	Washington	District of Columbia
United States	Triple O Research Institute /ID# 224863	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Maximum Observed Concentration (Cmax)	Maximum Observed Concentration (Cmax) of ABBV-181.	Up to approximately 36 weeks
Primary	Time to Cmax (Tmax)	Time to Cmax (Tmax) of ABBV-181.	Up to approximately 36 weeks
Primary	Observed Concentration (Ctrough)	Observed Concentration (Ctrough) at the end of the dosing intervals for ABBV-181.	Up to approximately 36 weeks
Primary	Area Under the Curve (AUCtau)	Area Under the Curve (AUCtau) during the dosing intervals for ABBV-181.	Up to approximately 36 weeks
Primary	Half-life (t1/2)	Half-life (t1/2) of ABBV-181 following the last dose.	Up to approximately 36 weeks