A Phase 3 Multicenter Study to Evaluate Efficacy, Safety, and Pharmacokinetics of Upadacitinib With Open-Label Induction, Randomized, Double-Blind Maintenance and Open-Label Long-Term Extension in Pediatric Subjects With Moderately to Severely Active Crohn's Disease and Inadequate Response, Intolerance, or Medical Contraindications to Corticosteroids, Immunosuppressants, and/or Biologic Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 168
- 主要终点
- Achievement of endoscopic response at Week 64 in participants who achieved clinical response per PCDAI at Week 12.
研究概览
简要总结
Crohn's disease (CD) is a long-lasting disease that causes severe inflammation (redness, swelling), in the digestive tract, most often affecting the bowels. It can cause many different symptoms including abdominal pain, diarrhea, tiredness, and weight loss. This study will assess how safe and effective oral Upadacitinib is in treating moderately to severely active Crohn's Disease in pediatric participants aged 2 to 18 years old who have had inadequate response, loss of response, intolerance, or medical contraindications to corticosteroids, immunosuppressants, and/or biologic therapy.
Upadacitinib (RINVOQ) is a drug approved in adults for moderate- to severely active CD and is being developed for moderate- to severely active CD in pediatric participants. This study is conducted in 2 periods: Period 1 is comprised of two phases: a 12-week open-label induction phase which means that the study doctor and participants know that participants will receive UPA Dose-A (or the adult equivalent based on body weight) followed by a 52-week double-blind maintenance phase meaning that neither the participants nor the study doctors will know which dose of upadacitinib will be given (UPA Dose B or Dose C). Period 2 is a 156-week open-label extension of Period 1. Approximately 110 pediatric participants with moderate to severely active CD will be enrolled at approximately 92 sites worldwide.
Participants will receive upadacitinib oral tablets once daily or oral solution twice daily at approximately the same time each day, with or without food. Participants will have a safety follow up for 30 days after discontinuation from any time point within the study.
There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend regular (weekly, monthly) visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Weight at Screening and Baseline must be >= 10 kg
- •Moderate to severe Crohn's Disease (CD) defined as Pediatric Crohn's Disease Activity Index (PCDAI) > 30 and endoscopic evidence of mucosal inflammation as documented by a centrally read SES-CD of >= 6 (or SES-CD of >=4 for isolated ileal disease) excluding the presence of narrowing component.
- •Documented diagnosis of CD prior to Baseline, confirmed by colonoscopy during the screening period, with exclusion of current infection, colonic dysplasia and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment of the investigator, must be available
- •Demonstrated an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators (IMMs), and/or biologic therapy or in whom use of those therapies is medically contraindicated. For participants in the US and South Korea, participants must have demonstrated an inadequate response, loss of response, or intolerance to one or more anti-TNFs (tumor necrosis factor).
排除标准
- •History of:
- •A diagnosis of CD prior to 2 years of age.
- •Currently known complications of CD such as:
- •Active abscess (abdominal or perianal);
- •Symptomatic bowel strictures;
- •More than 2 missing segments of the following 5 intestinal segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum;
- •Ostomy or ileoanal pouch;
- •Surgical bowel resection within the past 3 months prior to Baseline, or a history of more than 3 bowel resections.
- •Japan participants only: positive result of beta-D-glucan or two consecutive indeterminate results of beta-D-glucan during the Screening period (screening for Pneumocystis jiroveci infection)
- •History of any of the following:
- •Current diagnosis of ulcerative colitis (UC), indeterminate colitis, or monogenic inflammatory bowel disease (IBD);
- •Fulminant colitis or toxic megacolon;
- •Gastrointestinal (GI) perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment including history of volvulus and/or intussusception (telescoping of bowels);
- •Current diagnosis of any primary immune deficiency
- •Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; subjects with a history of gastric banding/segmentation are not excluded.
研究组 & 干预措施
Period 1: Open Label Induction Phase (Dose A)
All participants in the open label induction phase of Period 1 will receive upadacitinib Dose A for 12 weeks based on body weight.
干预措施: Upadacitinib (Drug)
Period 2: Open Label Long-Term Extension Phase Cohort 1
Participants receiving double-blind maintenance therapy with upadacitinib Dose B or upadacitinib Dose C daily in Period 1 who complete the Week 64 visit will receive upadacitinib Dose B daily for up to 156 weeks.
干预措施: Upadacitinib (Drug)
Period 2: Open Label Long-Term Extension Phase Cohort 2
Participants who were receiving rescue therapy with open-label upadacitinib Dose C during maintenance phase in Period 1 and completed the Week 64 visit will continue to receive upadacitinib Dose C daily for up to 156 weeks.
干预措施: Upadacitinib (Drug)
Period 2: Open Label Long-Term Extension Phase Cohort 3
Participants who did not achieve clinical response per PCDAI at Week 12 of Period 1 will receive an extended treatment with open-label upadacitinib Dose C daily for an additional 12 weeks. If they are responders after 12 weeks extended treatment, they will continue, otherwise they may be discontinued at the discretion of the investigator
干预措施: Upadacitinib (Drug)
Period 1: Double-Blind Maintenance Phase (Dose C)
Clinical responders per PCDAI at the end of open label induction phase of Period 1 will be randomly assigned to receive either upadacitinib Dose C or B for 52 weeks (oral solution dose will be based on body weight)
干预措施: Upadacitinib (Drug)
Period 1: Double-Blind Maintenance Phase (Dose B)
Clinical responders per PCDAI at the end of open label induction phase of Period 1 will be randomly assigned to receive Dose B or C for 52 weeks (oral solution dose will be based on body weight)
干预措施: Upadacitinib (Drug)
结局指标
主要结局
Achievement of endoscopic response at Week 64 in participants who achieved clinical response per PCDAI at Week 12.
时间窗: At Week 64
Endoscopic response is defined as \> 50% reduction in Simple Endoscopic Score for Crohn's Disease (SES-CD) score from Baseline (or for participants with a Baseline SES-CD of 4, at least a 2-point reduction from Baseline), as scored by a central reader.
Number of Participants with Adverse Events
时间窗: Through Week 156
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.
Percentage of participants who achieved clinical response per the Pediatric Crohn's Disease Activity Index (PCDAI) at Week 12, with clinical remission per the PCDAI at Week 64
时间窗: At Week 64
PCDAI is an index used to measure disease activity of pediatric patients with Crohn's disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. Clinical remission was defined as PCDAI ≤ 10.
次要结局
- Achievement of clinical remission per PCDAI(Week 12)
- Achievement of endoscopic remission(Week 12)
- Achievement of clinical response per PCDAI(Week 12)
- Achievement of corticosteroid (CS)-free clinical remission per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12(Week 64)
- Achievement of endoscopic response(Week 12)
- Achievement of clinical response per PCDAI at Week 64 in participants who achieved clinical response per PCDAI at Week 12(Week 64)
- Achievement of endoscopic remission at Week 64 in participants who achieved clinical response per PCDAI at Week 12(Week 64)