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)

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Human Immunodeficiency Virus (HIV)

Intervention / Treatment
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* Drug: ABBV-382
* Drug: ABBV-382
* Drug: Placebo for ABBV-382


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Immunodeficiency Virus, HIV, HIV-1, ABBV-382