A Randomized, Open Label, Multicentric, Parallel group, Active-Controlled Comparative Phase III Trial to Evaluate the Efficacy and Safety of Upadacitinib Extended Release Tablets in Comparison with Tofacitinib Tablets in Adults with moderately to severely active ulcerative colitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 15
- 主要终点
- Proportion of subjects achieving clinical remission at end of 8 weeks using modified Mayo score
研究概览
简要总结
This Study Titled an open label, multi-centre, randomized, parallel group, active controlled and comparative phase 3 clinical study to evaluate the efficacy and safety of Upadacitinib Extended Release Tablets 15mg, 30mg, 45mg in Adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more TNF blockers. Initially, subjects will be screened as per predefined eligibility criteria for the study.
Eligible 180 subjects will be enrolled to receive Upadacitinib or Tofacitinib. Subjects will be randomized in a 2:1 ratio. Group 1 will have 120 subjects and Group 2 will have 60 subjects. Group 1 (Treatment group): Upadacitinib Dose: The recommended induction dosage is 45 mg once daily for 8 weeks. The recommended maintenance dosage is 15 mg once daily. A maintenance dosage of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease. Discontinue Upadacitinib if adequate therapeutic response is not achieved with the 30 mg dosage. Use the lowest effective dosage needed to maintain response Group 2 (Control group): Tofacitinib Tablets 5mg, 10mg Dose: 10 mg twice daily for at least 8 weeks; then 5 or 10 mg twice daily. Use the lowest effective dose to maintain response.
Ulcerative colitis The efficacy and safety of upadacitinib was evaluated in three multicentre, double-blind, placebo-controlled Phase 3 clinical studies: two replicate induction studies, UC-1 (U-ACHIEVE Induction) and UC-2 (U-ACCOMPLISH), and a maintenance study UC-3 (U[1]ACHIEVE Maintenance). Disease activity was based on the adapted Mayo score (aMS, Mayo scoring system excluding Physician’s Global Assessment), which ranged from 0 to 9 and has three subscores that were each scored 0 (normal) to 3 (most severe): stool frequency subscore (SFS), rectal bleeding subscore (RBS) and a centrally-reviewed endoscopy subscore (ES).
Background information:
Upadacitinib was originally approved for the treatment of rheumatoid arthritis, but its indication has expanded to include ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, Protocol Number: MSN/CT/Upada/2023-2024 M/s. MSN Laboratories Private Limited Version/ Date: 1.2 Dated 12 Feb 2024 Confidential Page 34 of 77 and atopic dermatitis. For all of these indications, the patient must first have failed or been intolerant to anti-TNF therapy; the only exception is atopic dermatitis, as anti-TNFs are not indicated for its treatment. The dosing is generally higher for ulcerative colitis than for other indications: 45 mg daily induction dose for the first 8 weeks, then 30 mg daily. A lower dose of 15 mg (used for all other indications) is recommended in UC for those with renal or hepatic disease. Upadacitinib should be avoided in anyone with cirrhosis due to its hepatic metabolism.
Safety assessments will include physical & systemic examination, vital signs, ECGs, Laboratory parameters: Blood (hematology & biochemistry) and urinalysis
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Adult male or female subjects with age ≥18 years and ≤ 65 years of age at the time of screening.
- •2.Subjects who are willing and able to sign informed consent approved by an Independent Ethics Committee and Institutional Review Board for participation in the study and willing to adhere to all protocol procedures.
- •3.Subjects with moderately to severely (as assessed by the modified Mayo score) active ulcerative colitis (confirmed endoscopically prior to baseline) who have had an inadequate response or intolerance to one or more TNF blockers.
- •4.Male or female subjects of child-bearing potential must agree to use medically acceptable forms of contraception during the study.
- •5.Subject with a negative test for Tuberculosis with Mantoux Test.
排除标准
- •Subject with history of hypersensitivity to investigational products or to any of the excipient.
- •Participant with current diagnosis of Crohns disease or diagnosis of indeterminate colitis
- •Current diagnosis of fulminant colitis and or toxic megacolon
- •Known active bacterial, viral, fungal, mycobacterial, or other infection including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds.
- •Total white blood cell count less than 2,500- μL, absolute neutrophil count less than 1,500-μL platelet count less than 100,000-μL absolute lymphocyte count less than 800-μL and hemoglobin less than 10 g-dL.
- •Renal system: estimated glomerular filtration rate eGFR less than40 mL-minute-1.73 m
- •Subject has active TB or meets TB exclusionary parameters
- •Receipt of any live vaccine within 4 weeks prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 4 weeks after the last dose of study drug.
- •Subjects with medical history of Oncological Conditions since last 2 years
- •History of clinically significant drug or alcohol abuse within the last 6 months per Investigators judgment.
- •History of moderate to severe congestive heart failure New York Heart Association class III or IV
- •History of myocardial infarction, coronary stenting or CVA within 6 months prior to Screening.
- •Uncontrolled hypertension as defined by a persistent systolic blood pressure BP greater than 160 mmHg or diastolic BP greater than 100 mmHg. For subjects with known hypertension, the subjects BP must be stable for at least 4 weeks on current, stable anti-hypertensive medications.
- •Clinically relevant or significant ECG abnormalities, including ECG with QT interval corrected for heart rate QTc using Fridericias correction formula QTcF greater than 450 msec males or greater than 470 msec.
- •Infection requiring treatment with parenteral anti-infectives within 30 days, or oral anti-infectives within 14 days prior the first dose of study drug.
- •Subjects with clinically significant impaired hepatic function. SGOT & SGPT more than 3X the UNL and-or Total bilirubin more than 1.5X the UNL.
- •Subjects with suspected signs and symptoms of COVID-19-confirmed novel coronavirus infection or with a recent history of travel-contact with any COVID-19 positive subject-isolation-quarantine in the last 14 days
- •Female subjects who are pregnant or lactating or planning to become pregnant during the study period.
- •Females who are not ready to use acceptable contraceptive methods during the course of study.
- •Concurrent participation in another clinical trial or any investigational therapy within 90 days prior to signing informed consent.
- •Subjects with history of HIV and or Hepatitis B and or Hepatitis C.
- •Suspected inability or unwillingness to comply with the study procedures.
- •Subjects with clinically significant disorders that, in the opinion of the investigator, would result in jeopardizing subjects safety and efficacy of the drug.
- •Subject with a positive test for Tuberculosis with QuantiFERON-TB Gold test.
结局指标
主要结局
Proportion of subjects achieving clinical remission at end of 8 weeks using modified Mayo score
时间窗: Proportion of subjects achieving clinical remission at end of study using modified Mayo score consists of 3 components | Visit 1. Screening Visit Screening -14 days | Visit 2. Randomization Baseline Visit Day 0 | Visit 3. Week 1 or Day 7 pulse 2days window | Visit 4. Week 4 or Day 28 pulse 2 days window | Visit 5. Week 8 or Day 56 pulse 2 days window | Visit 6. Week 12 or Day 84 pulse 2 days window | Visit 7. Week 16 or Day 112 End of study pulse 2 days window
Proportion of subjects achieving Endoscopic improvement at the end of study.
时间窗: Proportion of subjects achieving clinical remission at end of study using modified Mayo score consists of 3 components | Visit 1. Screening Visit Screening -14 days | Visit 2. Randomization Baseline Visit Day 0 | Visit 3. Week 1 or Day 7 pulse 2days window | Visit 4. Week 4 or Day 28 pulse 2 days window | Visit 5. Week 8 or Day 56 pulse 2 days window | Visit 6. Week 12 or Day 84 pulse 2 days window | Visit 7. Week 16 or Day 112 End of study pulse 2 days window
次要结局
- Proportion of subjects achieving clinical remission at end of 8 weeks using modified Mayo score(Proportion of subjects achieving Endoscopic improvement at the end of study.)
研究者
Dr Aditi Datta
Biosite Research Private Limited