A Phase-II, Randomised, Double-blind, Parallel-group, Proof-of-concept Trial to Investigate ABBV-4083 Given for 7 or 14 Days or in Combination With Albendazole in Subjects With Onchocerca Volvulus Infection, Comprising: Part 1 to Investigate Safety, Tolerability, Efficacy for Dose-Ranging and Pharmacokinetics; Part 2 to Investigate Efficacy of Selected Doses, Safety, Tolerability and Pharmacokinetics
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 153
- 试验地点
- 2
- 主要终点
- Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules
研究概览
简要总结
Onchocerciasis is a major public health problem in affected countries that causes disease-induced disability, and overall loss of economic productivity. The purpose of this study is to determine how safe and effective ABBV-4083 in combination with albendazole is in treating participants with Onchocerciasis.
ABBV-4083 is an investigational drug being developed for the treatment of onchocerciasis. This study is conducted in 2 parts. In part 1, participants are randomly assigned to 1 of 5 groups, called treatment arms to determine the most efficient treatment combination. Each group receives a different treatment. In part 2, participants are randomly assigned to 1 of 4 treatment arms. Approximately 444 or 486 adult participants with a diagnosis of onchocerciasis will be enrolled in approximately 2 sites in Democratic Republic of Congo.
Participants in Part 1 will receive different treatment combinations of ABBV-4083 and/or albendazole and/or matching placebo capsules for 14 days. Participants in Part 2 will most effective treatment combination determined in Part 1 for 14 days followed by ivermectin or matching placebo capsules at Month 6. Duration of treatment is 24 months.
There may be 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 checking for side effects.
详细描述
The study was terminated at the conclusion of Part 1, and Part 2 of the study was not conducted.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Diagnosis of Onchocerca volvulus infection at time of Screening:
- •Presence of at least one excisable subcutaneous nodule/ onchocercoma detected on palpation;
- •O. volvulus infection diagnosed by skin snip method: documented mfpositivity on skin assessment on at least 2 out of 4 skin snips.
- •Body weight > 40 kg at Screening.
- •For women of child-bearing potential, acceptance of the requirement to use a highly effective form of birth control from Day 0 until at least 1 month after the final intake of study drug (Part 1: day 43; Part 2: 1 month after the administration of ivermectin or matching placebo at the Month 6 visit). Choice of birth control method must be clearly documented.
排除标准
- •Participation in any studies other than purely observational studies within 3 months prior to Screening, or during the trial, or within 5 times the half-life of the drug tested in the previous clinical trial or is currently in the follow-up period for any clinical trial.
- •Any vaccination within 4 weeks prior to investigational medicinal product (IMP) administration.
- •Acute infection and/or febrile illness requiring therapy within 14 days prior to IMP administration.
- •Administration of medication or herbal preparations as follows:
- •Administration of any medication (with the exception of diclofenac, paracetamol, ibuprofen and aspirin) or herbal preparation within 14 days prior to IMP administration;
- •Use of strong CYP3A inhibitors or inducers including but not limited to ritonavir, ketoconazole, rifampicin, phenytoin, phenobarbital, carbamazepine, cimetidine within 14 days or 10 half-lives, whichever is longer, prior to IMP administration;
- •Use of other drugs known to interact with albendazole i.e. praziquantel, theophylline or dexamethasone, within 14 days or 10 half-lives, whichever is longer, prior to IMP administration;
- •Antifilarial therapies, or medication that may have an antifilarial effect.
- •Requirement for and inability to avoid ivermectin during the first 6 months after IMP administration. Requirement for albendazole during the first 28 days after IMP administration or more than one dose per year thereafter given in MDA.
- •Presence of any of the following at Screening, that could interfere with the objectives of the trial or the safety of the participant, in the opinion of the Investigator:
- •Abnormal physical examination or laboratory findings;
- •Any clinically significant medical condition. Including, but not limited to significant acute or chronic liver or kidney condition or cardiovascular disease, active infection, current or previous epilepsy, known human immunodeficiency virus infection, disclosed by review of medical history or concomitant medication.
- •Ophthalmological history or conditions that could interfere with the objectives of the trial or compromise the safety of the subject in the opinion of the Investigator, assessed at Screening.
- •History of drug or alcohol abuse within 6 months prior to IMP administration.
- •Use of alcohol or drugs of abuse within 24 hours before IMP administration.
- •Clinically significant history of cardiac abnormality, and/or relevant pathological abnormalities in the ECG in the screening period.
- •Abnormal laboratory test results at Screening.
- •History of severe drug allergy, non-allergic drug reactions, severe adverse reaction to any drug, or multiple drug allergies.
- •Known hypersensitivity to any ingredient of the IMPs, including the active ingredient of ABBV-4083, macrolides, albendazole or to ivermectin or to any medication used during the study.
- •Blood donation within 8 weeks prior to Screening or blood transfusion received within 1 year prior to Screening.
- •Coincidental infection with high Loa loa load and/or Mansonella species or Wuchereria bancrofti, based on positive laboratory test at Screening.
- •Current hyperreactive onchodermatitis or severe manifestation due to onchocerciasis.
- •Any other past or current condition that the Investigator feels would exclude the participant from the study or place the subject at undue risk.
- •For women of child-bearing potential: pregnant, based on date of last menstrual period, and pregnancy test prior to first intake of IMP, or breastfeeding.
- •Unwilling or unable to comply with the requirements of the study protocol for the entire duration of the study, in the opinion of the Investigator.
- •Unable to participate in the study as per local law, if applicable.
研究组 & 干预措施
Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days
Participants received ABBV-4083 400 mg administered orally as capsules plus placebo capsules for albendazole for 7 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: ABBV-4083 (Drug)
Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days
Participants received ABBV-4083 400 mg administered orally as capsules plus placebo capsules for albendazole for 7 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: Placebo for ABBV-4083 (Drug)
Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days
Participants received ABBV-4083 400 mg administered orally as capsules plus placebo capsules for albendazole for 7 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: Placebo for Albendazole (Drug)
Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days
Participants received ABBV-4083 400 mg administered orally as capsules plus placebo capsules for albendazole for 7 days followed by ABBV-4083 400 mg administered orally as capsules for 7 days.
干预措施: ABBV-4083 (Drug)
Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days
Participants received ABBV-4083 400 mg administered orally as capsules plus placebo capsules for albendazole for 7 days followed by ABBV-4083 400 mg administered orally as capsules for 7 days.
干预措施: Placebo for Albendazole (Drug)
Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days
Participants received ABBV-4083 400 mg administered orally as capsules plus albendazole 400 mg capsules for 7 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: ABBV-4083 (Drug)
Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days
Participants received ABBV-4083 400 mg administered orally as capsules plus albendazole 400 mg capsules for 7 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: Placebo for ABBV-4083 (Drug)
Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days
Participants received ABBV-4083 400 mg administered orally as capsules plus albendazole 400 mg capsules for 7 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: Albendazole (Drug)
Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d
Participants received ABBV-4083 400 mg administered orally as capsules plus albendazole 400 mg capsules for 3 days followed by ABBV-4083 400 mg and placebo capsules for albendazole for 4 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: ABBV-4083 (Drug)
Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d
Participants received ABBV-4083 400 mg administered orally as capsules plus albendazole 400 mg capsules for 3 days followed by ABBV-4083 400 mg and placebo capsules for albendazole for 4 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: Placebo for ABBV-4083 (Drug)
Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d
Participants received ABBV-4083 400 mg administered orally as capsules plus albendazole 400 mg capsules for 3 days followed by ABBV-4083 400 mg and placebo capsules for albendazole for 4 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: Albendazole (Drug)
Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d
Participants received ABBV-4083 400 mg administered orally as capsules plus albendazole 400 mg capsules for 3 days followed by ABBV-4083 400 mg and placebo capsules for albendazole for 4 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: Placebo for Albendazole (Drug)
Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days
Participants received placebo for ABBV-4083 administered orally as capsules plus albendazole 400 mg capsules for 7 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: Placebo for ABBV-4083 (Drug)
Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days
Participants received placebo for ABBV-4083 administered orally as capsules plus albendazole 400 mg capsules for 7 days followed by placebo capsules for ABBV-4083 for 7 days.
干预措施: Albendazole (Drug)
结局指标
主要结局
Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules
时间窗: At Month 6
The Wolbachia endobacteria status of each live female adult worm was determined by immunohistology of nodules collected after nodulectomy at the Month 6 visit.
次要结局
- Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus Per Participant at Month 6(At Month 6)
- Part 1: Percentage of Live Female Adult Worms Out of All Female Adult Worms Per Participant at Month 6(At Month 6)
- Part 1: Percentage of Participants Without Microfilariae in Nodular Tissue at Month 6(At Month 6)
- Part 1: Percentage of Participants Without Skin Microfilariae at Month 3(At Month 3)
- Part 1: Percentage of Participants Without Skin Microfilariae at Month 6(At Month 6)
- Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 3(Baseline, Month 3)
- Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 6(Baseline, Month 6)
- Part 1: Percentage of Nodules That Contain at Least 1 Live Female Adult Worm Without Wolbachia Assessed by PCR at Month 6(At Month 6)