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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 41
- 试验地点
- 23
- 主要终点
- Number of Participants with Study Drug-Related Adverse Events Grade 3 or Higher
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body Mass Index (BMI) between 18.0 and 35 kg/m
- •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.
排除标准
- •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.
研究组 & 干预措施
Stage 1: Arm B
Participants will receive ABBV-181 dose A.
干预措施: ABBV-181 (Drug)
Stage 1: Arm A
Participants will receive placebo.
干预措施: Placebo (Drug)
Stage 1: Arm C
Participants will receive ABBV-181 dose B.
干预措施: ABBV-181 (Drug)
Stage 2: Arm D
Participants will receive Placebo.
干预措施: Placebo (Drug)
Stage 2: Arm E
Participants will receive ABBV-181 dose C.
干预措施: ABBV-181 (Drug)
结局指标
主要结局
Number of Participants with Study Drug-Related Adverse Events Grade 3 or Higher
时间窗: 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)
时间窗: 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
时间窗: Up to approximately 44 weeks
Adverse Events (AEs) Corresponding to Retroviral Rebound Syndrome.
Maximum Observed Concentration (Cmax)
时间窗: Up to approximately 36 weeks
Maximum Observed Concentration (Cmax) of ABBV-181.
Time to Cmax (Tmax)
时间窗: Up to approximately 36 weeks
Time to Cmax (Tmax) of ABBV-181.
Observed Concentration (Ctrough)
时间窗: Up to approximately 36 weeks
Observed Concentration (Ctrough) at the end of the dosing intervals for ABBV-181.
Area Under the Curve (AUCtau)
时间窗: Up to approximately 36 weeks
Area Under the Curve (AUCtau) during the dosing intervals for ABBV-181.
Half-life (t1/2)
时间窗: Up to approximately 36 weeks
Half-life (t1/2) of ABBV-181 following the last dose.
次要结局
未报告次要终点