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)

Sponsor

AbbVie (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04554966

Collaborator

(none)

Enrollment

Locations

Arms

25.3

Anticipated Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Human Immunodeficiency Virus (HIV)	Drug: ABBV-382 Drug: ABBV-382 Drug: Placebo for ABBV-382	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Apr 16, 2021

Anticipated Primary Completion Date :

Feb 26, 2023

Anticipated Study Completion Date :

May 26, 2023

Arms and Interventions

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
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
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
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
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 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

Outcome Measures

Primary Outcome Measures

Incidence of Study Drug-Related Grade 3 or Higher Adverse Events (AEs) [Up to Day 255]
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).
Maximum Observed Serum Concentration (Cmax) of ABBV-382 (Part A and Part B) [Up to Day 225]
Maximum observed serum concentration (Cmax) of ABBV-382.
Time to Cmax (Tmax) of ABBV-382 (Part A and Part B) [Up to Day 225]
Time to Cmax (Tmax) of ABBV-382.
Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUCt) of ABBV-382 (Part A) [Up to Day 112]
Area under the serum concentration-time curve (AUC) from time 0 to the time of last measurable concentration (AUCt) of ABBV-382.
Area Under the Serum Concentration-Time Curve From Time 0 to Infinite Time (AUCinf) of ABBV-382 (Part A) [Up to Day 112]
AUC from time 0 to infinite time (AUCinf) of ABBV-382.
Terminal Phase Elimination Rate Constant (β) of ABBV-382 (Part A) [Up to Day 112]
Terminal phase elimination rate constant of ABBV-382.
Terminal Phase Elimination Half-Life (t1/2) of ABBV-382 (Part A) [Up to Day 112]
Terminal phase elimination half-life of ABBV-382.
Observed Concentration at the End of the 4-Week Dosing Interval (Ctrough) of ABBV-382 (Part B) [Up to Day 225]
Observed concentration at the end of the 4-week dosing interval (Ctrough) of ABBV-382.
AUC During the 4-Week Dosing Interval (AUCtau) of ABBV-382 (Part B) [Up to Day 225]
AUC during the 4-week dosing interval (AUCtau) of ABBV-382.
Terminal Phase Elimination Half-Life (t1/2) of ABBV-382 (Part B) [Day 57 to Day 225]
Terminal phase elimination half-life (t1/2) of ABBV-382 will be estimated after the third dose only.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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