Study to Assess Adverse Events and How Intravenous (IV) or Subcutaneous (SC) ABBV-382 Moves Through the Body of Adult Participants With Human Immuno-Deficiency Virus (HIV-1)

A Phase 1b Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of ABBV-382 in Persons Living With HIV-1 (PLWH)

Human immuno-deficiency virus (HIV) is the virus that causes Acquired Immuno-Deficiency Syndrome (AIDS). HIV infection is considered to be a chronic disease requiring lifelong therapy. This study will evaluate how safe ABBV-382 is and how it is absorbed, distributed and eliminated from the body in adult participants with HIV-1 infection.

ABBV-382 is an investigational drug being developed for the treatment of HIV-1 infection. This study takes place in 2 parts. In Part A, participants with HIV-1 and no history of combination antiretroviral therapy (cART) or who are off cART for more than 3 months will be enrolled to receive ABBV-382. In Part B, participants with no virus in their blood and on maintenance cART will be enrolled into one of the intravenous (IV) or subcutaneous (SC) groups. In the IV groups, participants will receive either placebo or ABBV-382 whereas participants in the SC group will receive ABBV-382. There is 1 in 3 chance that participants will receive placebo (no drug) in Part B IV groups. The IV group in Part B is double-blinded which means neither the study doctors nor the participants will know who will be given study drug or placebo. Around 52 adult participants with HIV-1 infection will be enrolled at approximately 21 sites across the United States, including Puerto Rico.

Participants in Part A will receive an intravenous (IV) dose of ABBV-382 on Day 1. Participants in Part B will receive an IV or SC dose of ABBV-382 or placebo on Days 1, 29 and 57.

There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, and presence of side effects.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus (HIV)
• Intervention / Treatment: Drug: ABBV-382; Drug: ABBV-382; Drug: Placebo for ABBV-382

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00716-0377
    • Ponce Medical School Foundation /ID# 224231
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico /ID# 223923
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Franco Felizarta, Md /Id# 223815
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group /ID# 224125
    • San Francisco, California, United States, 94115-3037
      • Quest Clinical Research /ID# 223347
  • District of Columbia
    • Washington, District of Columbia, United States, 20037-3201
      • George Washington University Medical Faculty Associates /ID# 223493
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center /ID# 223500
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center /ID# 223498
    • Tampa, Florida, United States, 33614-7112
      • St. Joseph Comprehensive Research Institute /ID# 246232
    • West Palm Beach, Florida, United States, 33407-3100
      • Triple O Research Institute /ID# 223460
  • Georgia
    • Decatur, Georgia, United States, 30030
      • CenExcel iResearch LLC /ID# 225526
    • Morrow, Georgia, United States, 30260-2342
      • Infinite Clinical Trials - Morrow /ID# 225455
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics /ID# 224267
  • Michigan
    • Berkley, Michigan, United States, 48072-3046
      • Be Well Medical Center /ID# 223381
  • New York
    • Manhasset, New York, United States, 11030-3816
      • North Shore University Hospital Manhasset /ID# 223343
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital /ID# 224871
  • Texas
    • Austin, Texas, United States, 78705-3326
      • Central Texas Clinical Research /ID# 223378
    • Dallas, Texas, United States, 75208-4599
      • Prism Health North Texas - Oak Cliff Health Center /ID# 223237
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants, P.A /ID# 223236
    • Houston, Texas, United States, 77098-3900
      • The Crofoot Research Center, Inc /ID# 223383
  • Washington
    • Seattle, Washington, United States, 98104-3595
      • Peter Shalit, M.D. /ID# 224252

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body Mass Index (BMI) is >= 18.0 to <= 35.0 kg/m^2 after rounding to the tenths decimal.
• Must agree to use effective barrier protection during sexual activity for protection against Human Immunodeficiency Virus (HIV)-1 transmission through the last study visit.
• Female participants of childbearing potential must give consent to abide by contraception requirements.
• CD4+ count of >= 350 cells/μL at screening and at least once during the 48 weeks prior to screening.
• Negative screen for drugs of abuse and alcohol at screening. Participants with a positive marijuana screen may be included after evaluation by the investigator that the use would not interfere with adherence to study requirements, and that usage is not on a regular or chronic basis.
• Laboratory values must meet the acceptable criteria.

Part A participants must also have:

• Positive test result for anti-HIV antibody at screening.
• Plasma HIV-1 ribose nucleic acid (RNA) between 1,000 - 200,000 copies/mL at screening.
• Must be naive to combination antiretroviral therapy (cART) or have been off of cART for > 12 weeks or 5 half-lives of the drug (whichever is longer) prior to screening with documentation of at least one plasma HIV-1 RNA measurement greater than or equal to the lower limit of quantification (LLOQ) during the off cART period.
• Willing to hold on initiation of cART throughout the screening period and until 4 weeks after dosing.

Part B participants must also have:

• Positive test result for anti-HIV antibody at screening.
• Must have plasma HIV-1 RNA below the lower limit of quantification at screening and at least 24 weeks prior to screening. A single unconfirmed "blip" is allowed if preceded and followed by values below the lower limit of quantification.
• Must be HIV-1 infected on cART for at least 48 weeks prior to screening and on current cART regimen for at least 12 weeks prior to screening.

Exclusion Criteria:

• Female participants who are pregnant, breastfeeding, or considering becoming pregnant during the study.
• History or ongoing diagnosis of acquired immune deficiency syndrome (AIDS)-defining illness.
• History of or active immunodeficiency (other than HIV).
• Active autoimmune disease or history of autoimmune disease that has required systemic treatment.
• Clinically significant medical disorders (other than HIV-1 infection) that might expose the participant to undue risk of harm, confound study outcomes, or prevent the participant from completing the study.
• 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 or evidence of active tuberculosis (TB) disease or untreated latent TB infection at screening.
• No history of positive TB skin test or interferon gamma release assay (IGRA) or at screening which is considered clinically significant by the investigator. Participant with a history of a positive TB skin test or IGRA or at screening must have documentation of completion of a Centers for Disease Control and Prevention (CDC) recommended treatment course for latent TB. Any participant with suspicion for or diagnosis of active TB is excluded.
• Known psychiatric or substance abuse disorders that would interfere with adherence to study requirements.
• Currently enrolled in another interventional clinical study.
• Received immunomodulatory or immunosuppressive (including intravenous [IV]/oral [PO] steroids at any dose, but excluding steroids that are inhaled or topical) therapy within 24 weeks prior to the first dose of study drug.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: ABBV-382 Dose A; Participants will receive intravenous (IV) ABBV-382 dose A on Day 1.	Drug: ABBV-382; Intravenous (IV) infusion; Drug: ABBV-382; Subcutaneous (SC) injection
Experimental: Part A: ABBV-382 Dose B; Participants will receive intravenous (IV) ABBV-382 dose B on Day 1.	Drug: ABBV-382; Intravenous (IV) infusion; Drug: ABBV-382; Subcutaneous (SC) injection
Experimental: Part B: Intravenous Cohort: ABBV-382 Dose A; Participants will receive intravenous (IV) ABBV-382 dose A on Days 1, 29 and 57.	Drug: ABBV-382; Intravenous (IV) infusion; Drug: ABBV-382; Subcutaneous (SC) injection
Placebo Comparator: Part B: Intravenous Cohort: Placebo for ABBV-382 Dose A; Participants will receive intravenous (IV) placebo for ABBV-382 dose A on Days 1, 29 and 57.	Drug: Placebo for ABBV-382; Intravenous (IV) infusion
Experimental: Part B: Intravenous Cohort: ABBV-382 Dose B; Participants will receive intravenous (IV) ABBV-382 dose B on Days 1, 29 and 57.	Drug: ABBV-382; Intravenous (IV) infusion; Drug: ABBV-382; Subcutaneous (SC) injection
Experimental: Part B: Subcutaneous Cohort: ABBV-382; Participants will receive subcutaneous (SC) ABBV-382 dose C on Days 1, 29 and 57.	Drug: ABBV-382; Intravenous (IV) infusion; Drug: ABBV-382; Subcutaneous (SC) injection
Placebo Comparator: Part B: Intravenous Cohort: Placebo for ABBV-382 Dose B; Participants will receive intravenous (IV) placebo for ABBV-382 dose B on Days 1, 29 and 57.	Drug: Placebo for ABBV-382; Intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Study Drug-Related Grade 3 or Higher Adverse Events (AEs)	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 study drug as either "Reasonable Possibility" or "No Reasonable Possibility" and will assess the severity of each adverse event from Grade 1 (mild) to Grade 4 (potentially life-threatening).	Up to Day 255
Maximum Observed Serum Concentration (Cmax) of ABBV-382 (Part A and Part B)	Maximum observed serum concentration (Cmax) of ABBV-382.	Up to Day 225
Time to Cmax (Tmax) of ABBV-382 (Part A and Part B)	Time to Cmax (Tmax) of ABBV-382.	Up to Day 225
Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUCt) of ABBV-382 (Part A)	Area under the serum concentration-time curve (AUC) from time 0 to the time of last measurable concentration (AUCt) of ABBV-382.	Up to Day 112
Area Under the Serum Concentration-Time Curve From Time 0 to Infinite Time (AUCinf) of ABBV-382 (Part A)	AUC from time 0 to infinite time (AUCinf) of ABBV-382.	Up to Day 112
Terminal Phase Elimination Rate Constant (β) of ABBV-382 (Part A)	Terminal phase elimination rate constant of ABBV-382.	Up to Day 112
Terminal Phase Elimination Half-Life (t1/2) of ABBV-382 (Part A)	Terminal phase elimination half-life of ABBV-382.	Up to Day 112
Observed Concentration at the End of the 4-Week Dosing Interval (Ctrough) of ABBV-382 (Part B)	Observed concentration at the end of the 4-week dosing interval (Ctrough) of ABBV-382.	Up to Day 225
AUC During the 4-Week Dosing Interval (AUCtau) of ABBV-382 (Part B)	AUC during the 4-week dosing interval (AUCtau) of ABBV-382.	Up to Day 225
Terminal Phase Elimination Half-Life (t1/2) of ABBV-382 (Part B)	Terminal phase elimination half-life (t1/2) of ABBV-382 will be estimated after the third dose only.	Day 57 to Day 225

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2021
• Primary Completion (Actual): August 14, 2023
• Study Completion (Actual): August 14, 2023

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Human Immunodeficiency Virus; ABBV-382
• 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; Urogenital Diseases; Genital Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
• Other Study ID Numbers: M19-966

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