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

• ClinicalTrials.gov Identifier: NCT04223804
• Recruitment Status: Completed
• First Posted: January 10, 2020
• Last Update Posted: March 9, 2023
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: January 8, 2020
• First Posted Date: January 10, 2020
• Last Update Posted Date: March 9, 2023
• Actual Study Start Date: January 30, 2020
• Actual Primary Completion Date: February 27, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 5, 2022)

• Number of Participants with Study Drug-Related Adverse Events Grade 3 or Higher [ Time Frame: Up to approximately 44 weeks ]
  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.
• Number of Participants with Study Drug-Related Immune-Related Adverse Events (IRAE) [ Time Frame: Up to approximately 44 weeks ]
  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.
• Number of Participants with Adverse Events (AEs) Corresponding to Retroviral Rebound Syndrome [ Time Frame: Up to approximately 44 weeks ]
  Adverse Events (AEs) Corresponding to Retroviral Rebound Syndrome.
• Maximum Observed Concentration (Cmax) [ Time Frame: Up to approximately 36 weeks ]
  Maximum Observed Concentration (Cmax) of ABBV-181.
• Time to Cmax (Tmax) [ Time Frame: Up to approximately 36 weeks ]
  Time to Cmax (Tmax) of ABBV-181.
• Observed Concentration (Ctrough) [ Time Frame: Up to approximately 36 weeks ]
  Observed Concentration (Ctrough) at the end of the dosing intervals for ABBV-181.
• Area Under the Curve (AUCtau) [ Time Frame: Up to approximately 36 weeks ]
  Area Under the Curve (AUCtau) during the dosing intervals for ABBV-181.
• Half-life (t1/2) [ Time Frame: Up to approximately 36 weeks ]
  Half-life (t1/2) of ABBV-181 following the last dose.

Original Primary Outcome Measures (submitted: January 8, 2020)

• Number of Participants with Study Drug-Related Adverse Events Grade 3 or Higher [ Time Frame: Up to approximately 44 weeks ]
  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.
• Number of Participants with Study Drug-Related Immune-Related Adverse Events (IRAE) [ Time Frame: Up to approximately 44 weeks ]
  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 DAIDS (v2.1) AE grading scale.
• Number of Participants with Adverse Events (AEs) Corresponding to Retroviral Rebound Syndrome [ Time Frame: Up to approximately 44 weeks ]
  Adverse Events (AEs) Corresponding to Retroviral Rebound Syndrome
• Maximum Observed Concentration (Cmax) [ Time Frame: Up to approximately 28 weeks ]
  Maximum Observed Concentration (Cmax) of ABBV-181
• Time to Cmax (Tmax) [ Time Frame: Up to approximately 28 weeks ]
  Time to Cmax (Tmax) of ABBV-181
• Observed Concentration (Ctrough) [ Time Frame: Up to approximately 28 weeks ]
  Observed Concentration (Ctrough) at the end of the 4-week dosing interval for ABBV-181.
• Area Under the Curve (AUCtau) [ Time Frame: Up to approximately 28 weeks ]
  Area Under the Curve (AUCtau) during the 4-week dosing interval for ABBV-181.
• Half-life (t1/2) [ Time Frame: Up to approximately 28 weeks ]
  Half-life (t1/2) of ABBV-181 for the second dose.

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: January 8, 2020)

Peripheral PD-1 Receptor Saturation [ Time Frame: Up to approximately 28 weeks ]

Peripheral PD-1 Receptor Saturation on CD4+ and CD8+ T cell subsets.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of ABBV-181 (Budigalimab) in Adult Participants With Human Immunodeficiency Virus (HIV)-1
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment

Condition

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

Intervention

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

Study Arms

• Placebo Comparator: Stage 1: Arm A
  Participants will receive placebo.
  Intervention: Drug: Placebo
• Experimental: Stage 1: Arm B
  Participants will receive ABBV-181 dose A.
  Intervention: Drug: ABBV-181
• Experimental: Stage 1: Arm C
  Participants will receive ABBV-181 dose B.
  Intervention: Drug: ABBV-181
• Placebo Comparator: Stage 2: Arm D
  Participants will receive Placebo.
  Intervention: Drug: Placebo
• Experimental: Stage 2: Arm E
  Participants will receive ABBV-181 dose C.
  Intervention: Drug: ABBV-181

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 19, 2022): 41
• Original Estimated Enrollment (submitted: January 8, 2020): 50
• Actual Study Completion Date: February 27, 2023
• Actual Primary Completion Date: February 27, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Puerto Rico, United States
• Removed Location Countries: France

Administrative Information

• NCT Number: NCT04223804
• Other Study ID Numbers: M19-939; 2019-004866-16 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: March 2023