A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study in Healthy Participants and Multiple Dose Study in Participants With Ulcerative Colitis to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-66525433
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Part 1, 2 and 3: Number of Participants with Chemistry Laboratory Abnormalities
研究概览
简要总结
The purpose of this study is to evaluate safety and tolerability of JNJ 66525433 compared with placebo after administration of: 1) single ascending oral doses of JNJ 66525433 administered to healthy participants (Part 1), 2) multiple, ascending oral doses of JNJ 66525433, administered to healthy participants once daily over 14 consecutive days (Part 2), and 3) multiple oral doses of JNJ 66525433, administered once daily over 14 consecutive and once daily over 42 consecutive days in participants with ulcerative colitis (UC) (Part 3).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Part 1 and Part 2, healthy volunteers
- •Have a body mass index (BMI) between 18 and 30 kilogram per meter square (kg/m^2) (BMI = weight/height), inclusive, and a body weight of no less than 50 kilogram (kg) and maximum weight of 100 kg
- •Have normal bowel movements, ranging from 1 to 3 times daily to every other day and have normal consistencies according to the Bristol Stool Scale, ranging from 3 to 5 at admission
- •For Part 3, participants with ulcerative colitis (UC)
- •Have a clinical diagnosis of UC at least 3 months before screening
- •Have moderately to severely active UC, defined as a Week 0 mayo score of 6 to 12, inclusive, based on central read of the video endoscopy performed during the screening
- •Have a greater than or equal to (>=) 2 endoscopy subscore of the Week 0 mayo score based on central read of the video endoscopy performed during the screening
排除标准
- •For Part 1 and Part 2, healthy volunteers
- •History of liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
- •Known allergies, hypersensitivity, or intolerance to antisense oligonucleotides, JNJ-66525433 or its excipients
- •For Part 3, participants with UC
- •Has UC limited to the rectum only or to <20 centimeter (cm) of the colon evaluated by endoscopy at screening
- •Presence of a stoma
- •Presence or history of a fistula at any time
- •COVID-related
- •If a participant is excluded due to recent Coronavirus disease (COVID-19) related features, the reason for screen failure should be documented in the case report form under the exclusion criterion of having a condition for which participation would not be in the participant's interest or could confound study assessments
- •The field of COVID-related testing (for presence of, and immunity to, the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] virus) is rapidly evolving. Additional testing may be performed as part of screening and/or during the study if deemed necessary by the investigator and in accordance with current regulations / guidance from authorities / standards of care
研究组 & 干预措施
JNJ-66525433
Participants will receive JNJ-66525433 in increasing dose level 1 to dose level 4 in Parts 1, 2, and dose level 3 in part 3.
干预措施: JNJ-66525433 (Drug)
Placebo
Participants will receive matching placebo in Parts 1, 2 and 3.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1, 2 and 3: Number of Participants with Chemistry Laboratory Abnormalities
时间窗: Up to 224 Days
Number of participants with chemistry laboratory abnormalities will be reported.
Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability
时间窗: Up to 224 Days
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Any AE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days will be considered as TEAE.
Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities
时间窗: Up to 224 Days
Number of participants with vital sign abnormalities (temperature), pulse/heart rate, respiratory rate and blood pressure) will be reported.
Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities
时间窗: Up to 224 Days
Number of participants with physical examination abnormalities will be reported.
Part 1, 2 and 3: Number of Participants with Hematology Laboratory Abnormalities
时间窗: Up to 224 Days
Number of participants with hematology laboratory abnormalities will be reported.
Part 2 and 3: Number of Participants with Abnormalities in High Sensitivity C- Reactive Protein (hs-CRP)
时间窗: Up to 224 Days
Number of participants with abnormalities in hs-CRP will be reported using a validated, high sensitivity CRP assay.
Part 1, 2 and 3: Number of Participants with Urinalysis Laboratory Abnormalities
时间窗: Up to 224 Days
Number of participants with abnormalities in urinalysis will be reported.
Part 2 and 3: Number of Participants with Abnormalities in Fecal Calprotectin
时间窗: Up to 224 Days
Assays for fecal calprotectin will be performed using a validated method.
Part 2 and 3: Incidence of Enteric Pathogens in Stool Samples
时间窗: Up to 224 Days
Stool culture and Clostridium difficile toxin assay will be used for enteric pathogen assessment.
Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities
时间窗: Up to 224 Days
Number of participants with ECG abnormalities will be reported.
次要结局
- Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing(Up to Day 14)
- Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433(Up to 224 Days)
- Part 3: Endoscopic Subscore(Up to Day 84)
- Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score(Days 1, 7, 14, 28, 43, 70 and 84)
- Part 3: Mayo Score(Up to Day 84)
- Part 3: Partial Mayo Score(Up to Day 70)
- Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels(Up to 182 Days)
- Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations(Up to 182 Days)
- Faecal Concentrations of JNJ-66525433 After Two Meal Timing Conditions(Predose, up to 120 hours postdose)
- Plasma Concentrations of JNJ-66525433 After Two Meal Timing Conditions(Up to 22 Days)