Clinical trial NCT04554966: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Human Immunodeficiency Virus (HIV)
Keywords: Human Immunodeficiency Virus
HIV
HIV-1
ABBV-382
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-09-18
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Study Drug-Related Grade 3 or Higher Adverse Events (AEs)
timeFrame: Up to Day 255
measure: Maximum Observed Serum Concentration (Cmax) of ABBV-382 (Part A and Part B)
timeFrame: Up to Day 225
measure: Time to Cmax (Tmax) of ABBV-382 (Part A and Part B)
timeFrame: Up to Day 225
measure: Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUCt) of ABBV-382 (Part A)
timeFrame: Up to Day 112
measure: Area Under the Serum Concentration-Time Curve From Time 0 to Infinite Time (AUCinf) of ABBV-382 (Part A)
timeFrame: Up to Day 112
measure: Terminal Phase Elimination Rate Constant (β) of ABBV-382 (Part A)
timeFrame: Up to Day 112
measure: Terminal Phase Elimination Half-Life (t1/2) of ABBV-382 (Part A)
timeFrame: Up to Day 112
measure: Observed Concentration at the End of the 4-Week Dosing Interval (Ctrough) of ABBV-382 (Part B)
timeFrame: Up to Day 225
measure: AUC During the 4-Week Dosing Interval (AUCtau) of ABBV-382 (Part B)
timeFrame: Up to Day 225
measure: Terminal Phase Elimination Half-Life (t1/2) of ABBV-382 (Part B)
timeFrame: Day 57 to Day 225
Secondary outcomes:
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Franco Felizarta, Md /Id# 223815
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group /ID# 224125
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research /ID# 223347
state: California
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates /ID# 223493
state: District of Columbia
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center /ID# 223500
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center /ID# 223498
state: Florida
city: Tampa
country: United States
facility: St. Joseph Comprehensive Research Institute /ID# 246232
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute /ID# 223460
state: Florida
city: Decatur
country: United States
facility: CenExcel iResearch LLC /ID# 225526
state: Georgia
city: Morrow
country: United States
facility: Infinite Clinical Trials - Morrow /ID# 225455
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics /ID# 224267
state: Iowa
city: Berkley
country: United States
facility: Be Well Medical Center /ID# 223381
state: Michigan
city: Manhasset
country: United States
facility: North Shore University Hospital Manhasset /ID# 223343
state: New York
city: Cincinnati
country: United States
facility: The Christ Hospital /ID# 224871
state: Ohio
city: Austin
country: United States
facility: Central Texas Clinical Research /ID# 223378
state: Texas
city: Dallas
country: United States
facility: Prism Health North Texas - Oak Cliff Health Center /ID# 223237
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A /ID# 223236
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center, Inc /ID# 223383
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, M.D. /ID# 224252
state: Washington
city: Ponce
country: Puerto Rico
facility: Ponce Medical School Foundation /ID# 224231
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico /ID# 223923
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: