TOFACITINIB for Ulcerative colitis

Inclusion criteria

• {"criterion_text":"- Patient has given written informed consent form to participate in the clinical trial.\n- Patient is male or female aged 18 to 75 years, inclusive.\n- Patient who has ulcerative colitis, confirmed by endoscopic or radiographic and histological criteria. Histopathology report supporting the diagnosis must be available in the source documents prior to the randomization.\n- Patient who has not achieved clinical remission, defined as the total Mayo score of ≤ 2 with all subscores of ≤ 1 and Mayo rectal bleeding subscore of 0, despite 8-weeks of treatment with vedolizumab.\n- The following treatments for ulcerative colitis are allowed: a. budesonide taken orally at a dose not exceeding 9 mg/day, if taken at a stable dose for at least 2 weeks prior to the randomization, b. other corticosteroids taken orally at a dose not exceeding 20 mg/day of prednisone, if taken at a stable dose for at least 2 weeks prior to the randomization, c. 5-Aminosalicylates (5-ASA), if taken at a stable dose for at least 4 weeks prior to the randomization.\n- For female patients of childbearing potential and male patients and their partners of childbearing potential who agree to use one of the following medically acceptable methods of contraception during the course of the study and for 6 moths following the discontinuation of study drug: - highly effective method of contraception that are user independent, with a failure rate of <1% per year when used consistently and correctly: • implantable progestogen-only hormone contraception associated with inhibition of ovulation; • intrauterine device (IUD); • intrauterine hormone - releasing system (IUS), • bilateral tubal occlusion; • partner after a documented vasectomy (provided that the partner is the sole sexual partner of the woman of childbearing potential and the absence of sperm has been confirmed); - highly effective method of contraception that are user dependent, with a failure rate of <1% per year when used consistently and correctly: • progestogen-only hormone contraception associated with inhibition of ovulation (oral or injectable) • combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: - oral - intravaginal - transdermal - injectable The use of the aforementioned methods also applies to women and men who have had surgical sterilization within 6 months prior to the date of informed consent. A woman of childbearing potential is defined as a woman from the onset of her first menarche and until becoming postmenopausal (defined as age >45 and no menses for at least 12 months without an alternative medical cause), unless permanently sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral oophorectomy). Menopausal females must have experienced their last period more than 12 months prior to the date of informed consent to be classified as not childbearing potential. Women and men who have had surgical sterilization more than 6 months prior to the date of informed consent are considered as not childbearing potential."}

Exclusion criteria

• {"criterion_text":"- Allergies to any of the excipients of infliximab or tofacitinib or any other murine and/or human proteins or has hypersensitivity to immunoglobulin products.\n- Use of exclusive enteral nutrition for more than 3 consecutive days within a month or any single day of exclusive enteral nutrition within 2 weeks prior to the randomization.\n- Live or live - attenuated vaccine within 4 weeks prior to the randomization.\n- Abnormalities in laboratory tests performed at screening: a. Serum creatinine ≥ 1.5 × upper limit of normal (ULN) or an estimated creatinine clearance level (eGFR) ≤ 50 ml/min (calculated from the Cockcroft-Gault formula), b. Serum alanine aminotransferase ≥ 2.0 × ULN, c. Serum aspartate aminotransferase ≥ 2.0 × ULN, d. Serum total bilirubin ≥ 1.5 × ULN, e. Hemoglobin < 8.5 g/dl (SI units: < 85 g/l or 5.28 mmol/l ), f. White blood cell count < 3.5 × 10^3 cells/μl (SI units: <3.5×10^9 cells/l), g. Neutrophil count < 1.5 × 10^3 cells/μl (SI units: <1.5×10^9 cells/l), h. Platelet count < 100 × 10^3 cells/μl (SI units: <100×10^9 cells/l). i. Positive HBsAg result, j. Positive HBV DNA result, k. Positive HCV RNA result, l. Positive anti-HIV result, m. Positive or twice inconclusive Quantiferon-TB Gold test result.\n- Patient who has a current or history of any of the following infections: a. Known infection with hepatitis B or hepatitis C (active or carrier state). However, a patient who is without cirrhosis of liver and recovered from a past hepatitis B or hepatitis C infection can be enrolled. A patient with a history of cured hepatitis B or C who does not have cirrhosis of liver can be enrolled but the following conditions must be met on screening: -a negative HBsAg and HBV DNA result for a patient with hepatitis B, - a negative HCV RNA result in the case of a patient with hepatitis C. b. Known infection with human immunodeficiency virus (HIV). c. Acute infection requiring oral antibiotics within 2 weeks or parenteral injection within 4 weeks prior to the randomization. d. Recurrent hemiplegia. e. Other recurrent or chronic infection, significant in the investigator’s opinion, within 6 weeks prior to the randomization. f. Current or past granulomatous infections or opportunistic infections (e.g., Pneumocystis carinii, aspergillosis, or mycobacteriosis [infection caused by nontuberculous mycobacteria]) or invasive fungal infection (e.g., histoplasmosis). g. Known cytomegalovirus infection within 6 months prior to the randomization. h. Evidence of Clostridioides difficile toxin in stool within 3 months prior to the randomization. i. Patient who has a current diagnosis of active TB or a history of active TB. Patient who has any evidence of history of active TB cannot be enrolled despite sufficient documentation of complete resolution of active TB. j. \tPatient who has had exposure to person(s) with active TB (e.g., first-degree relative, co-worker, roommate). k. Current diagnosis of latent TB at screening (defined as a positive interferon gamma assay [IGRA] without clinical signs of active tuberculosis and with a negative examination of chest x-ray from the qualifying visit for vedolizumab treatment). l. Other serious infections, in the investigator’s opinion, within 6 months prior to the randomization.\n- Medical condition including 1 or more of the following: a. Evidence of toxic megacolon b. Diagnose of Crohn’s disease or indeterminate colitis. c. Evidence of fixed symptomatic stenosis or obstruction of the large intestine d. Evidence of colonic mucosal dysplasia or adenomatous polyps. However, a patient whose adenomatous polyps are completely removed and free of polyps at the randomization can be enrolled. For a patient who has an increased risk for colorectal cancer, it is necessary to confirm the absence of adenomatous polyps and mucosal dysplasia with a colonoscopy (the result must be available in the source documentation): - if the patient is ≥ 45 years of age, a colonoscopy within 5 years prior to the randomization is required - if the patient, regardless of age, has extensive colitis for ≥ 8 years or disease limited to left side of colon (distal to splenic flexure) for ≥10 years, a colonoscopy performed within 1 year prior to the randomization is required e. Body mass index ≥ 35 kg/m2. f. \tUncontrolled diabetes mellitus. g.\tUncontrolled hypertension (as defined by systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg). h.\tA known malignancy within 5 years prior to the randomization, except completely excised and cured squamous carcinoma in situ of the uterine cervix, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma. i.\tHistory of lymphoma, lymphoproliferative disease, or bone marrow hyperplasia. j.\tNew York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled cardiac disease (unstable angina or clinically significant electrocardiogram [ECG] abnormalities), or myocardial infarction within 6 months prior to the randomization. k.\tHistory of organ transplantation, including corneal graft/transplantation. l.\tAny uncontrolled, clinically significant respiratory disease in the investigator’s opinion, including but not limited to chronic obstructive pulmonary disease, asthma, bronchiectasis, or pleural effusion. m.\tPrevious diagnosis or symptoms suggestive of demyelinating disorders, including multiple sclerosis and Guillain-Barré syndrome. n.\tAny condition significantly affecting the nervous system (e.g., neuropathic conditions or nervous system damage). o.\tAny other serious acute or chronic medical, or psychiatric conditions that may increase the risk associated with study participation or investigational product administration or that may interfere with the interpretation of study results.\n- Current or history of alcohol abuse within 12 months prior to the randomization.\n- Treatment with any other investigational device or medical product within 4 weeks prior to the randomization or 5 half-lives of the drug, whichever is longer.\n- Female patients who are currently pregnant or planning to become pregnant within 6 months of the last dose of study drug.\n- Female patients who are currently breastfeeding planning to breastfeed within 6 months of the last dose of study drug.\n- Lack of cooperation from the patient.\n- Patient who has received any of the following treatments: a. Within 2 weeks prior to the randomization: - budesonide taken orally in excess of 9 mg/day, - other GCSs taken orally in excess of 20 mg/day prednisone, - GCSs administered parenterally, - rectally administered medications containing corticosteroids or 5-ASA b. Within 3 weeks prior to the randomization: - apheresis (e.g., Adacolumn apheresis), c. \tWithin 4 weeks prior to the randomization administration of parenteral antibiotics d. Within 8 weeks prior to the randomization initiation of treatment with the following drugs: - azathioprine, - 6-mercaptopurine (6-MP), - methotrexate (MTX),\n- Patient who has received any of the following treatments due to ulcerative colitis or other disease: a. within 8 weeks prior to the randomization: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, b. within 12 months prior to the randomization: alkylating agents, c. ever: infliximab, ustekinumab.tofacitinib\n- Currently require or are anticipated to require surgical intervention for ulcerative colitis during the study.\n- Abdominal surgery for, including but not limited to, active gastrointestinal bleeding, peritonitis, intestinal obstruction, gastrointestinal resection, or intra-abdominal or pancreatic abscess requiring surgical drainage within 6 months prior to the randomization.\n- Extensive colonic resection (subtotal and total colectomy) prior to the randomization.\n- Stoma (e.g., ileostomy or colostomy) within 6 months prior to the randomization.\n- Nonautologous stem cell therapy (e.g. Prochymal) within 12 months prior to the randomization.\n- Use of total parenteral nutrition within a month prior to the randomization."}

Primary endpoints

• {"endpoint_text":"- Percentage of sustained corticosteroid-free remissions at week 52, sustained from week 8 onward with a maximum 11-week regimen of corticosteroids tapering. Clinical remission defined as the total Mayo score of ≤ 2 with all subscores of ≤ 1 and Mayo rectal bleeding subscore of 0","definition_or_measurement_approach":"Sustained corticosteroid-free remission at week 52, sustained from week 8 onward with up to an 11-week steroid taper. Clinical remission defined as total Mayo score ≤ 2 with all subscores ≤ 1 and Mayo rectal bleeding subscore = 0."}

Secondary endpoints

• {"endpoint_text":"- Percentage of clinical response at Week 8, Week 22 and Week 52, defined as a decrease in the total Mayop score of at least 3 points and at least 30% from the baseline value, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.","definition_or_measurement_approach":"Clinical response at Weeks 8, 22, 52 defined as decrease in total Mayo score ≥3 points and ≥30% from baseline plus either rectal bleeding subscore decrease ≥1 or rectal bleeding subscore of 0 or 1."}
• {"endpoint_text":"- Percentage of clinical remission at Week 8, defined as the total Mayo score of ≤ 2 with all subscores of ≤ 1 and Mayo rectal bleeding subscore of 0.","definition_or_measurement_approach":"Clinical remission at Week 8 defined as total Mayo score ≤2 with all subscores ≤1 and rectal bleeding subscore = 0."}
• {"endpoint_text":"- Percentage of deaths from ulcerative colitis at Week 8, Week 22, and Week 52.","definition_or_measurement_approach":"Proportion of patients who die from ulcerative colitis at Weeks 8, 22, and 52."}
• {"endpoint_text":"- The cumulative dose of corticosteroids used during the current flare of ulcerative colitis at Week 52.","definition_or_measurement_approach":"Cumulative corticosteroid dose during current flare measured up to Week 52."}
• {"endpoint_text":"- Percentage of patients who achieved mucosal healing at Week 8, Week 22, and Week 52, defined as the Mayo Endoscopic Score of ≤ 1.","definition_or_measurement_approach":"Mucosal healing defined as Mayo Endoscopic Score ≤1 at Weeks 8, 22, 52."}
• {"endpoint_text":"- Percentage of patients who achieved histologic – endoscopic mucosal healing at Week 8, Week 22, and Week 52, defined as achieving a combination of histologic remission and mucosal healing, as defined below: - histologic remission, defined as an absolute Robarts Histopathological Index (RHI) score of 3 points or less - mucosal healing, defined as the Mayo Endoscopic Score of ≤ 1.","definition_or_measurement_approach":"Histologic–endoscopic mucosal healing defined as both RHI ≤3 (histologic remission) and Mayo Endoscopic Score ≤1 (mucosal healing) at Weeks 8, 22, 52."}
• {"endpoint_text":"- Percentage of patients who achieved deep histologic – endoscopic mucosal healing at Week 8, Week 22, and Week 52, defined as achieving a combination of histologic remission and endoscopic normalization, as defined below: - histologic remission, defined as an absolute Robarts Histopathological Index (RHI) score of 3 points or less - endoscopic normalization, defined as the Mayo Endoscopic Score of 0.","definition_or_measurement_approach":"Deep histologic–endoscopic mucosal healing defined as RHI ≤3 and Mayo Endoscopic Score = 0 at Weeks 8, 22, 52."}
• {"endpoint_text":"- Change from baseline value in quality of life measured by SIBDQ, PROMIS-29 v.2.1, WPAI:GH v.2.2 and PSQI questionnaires, at Week 8, Week 22, and Week 52.","definition_or_measurement_approach":"Change from baseline in QoL as measured by SIBDQ, PROMIS-29 v2.1, WPAI:GH v2.2 and PSQI at Weeks 8, 22, 52."}
• {"endpoint_text":"- Occurrence of severe adverse events at Week 8, Week 22, and Week 52.","definition_or_measurement_approach":"Proportion of patients with severe adverse events recorded up to Weeks 8, 22, 52."}
• {"endpoint_text":"- Occurrence of non-severe adverse events at Week 8, Week 22, and Week 52.","definition_or_measurement_approach":"Proportion of patients with non-severe adverse events recorded up to Weeks 8, 22, 52."}
• {"endpoint_text":"- Occurrence of death from any cause at Week 8, Week 22, and Week 52.","definition_or_measurement_approach":"All-cause mortality at Weeks 8, 22, 52."}
• {"endpoint_text":"- Occurrence of MACE events, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, at Week 8, Week 22, and Week 52.","definition_or_measurement_approach":"Occurrence of MACE (cardiovascular death, non-fatal MI, non-fatal stroke) at Weeks 8, 22, 52."}
• {"endpoint_text":"- Occurrence of tuberculosis at Week 8, Week 22, and Week 52.","definition_or_measurement_approach":"Incidence of tuberculosis diagnoses at Weeks 8, 22, 52."}
• {"endpoint_text":"- Occurrence of hemiplegia at Week 8, Week 22, and Week 52.","definition_or_measurement_approach":"Occurrence of hemiplegia/presentation of shingles (as listed) at Weeks 8, 22, 52."}

Methods

• Recruitment arrangements document available (K1_ Recruitment arrangements_Procedura swiadomej zgody) and recruitment material document (K2_Recruitment material_Ogoszenie o badaniu) are listed in the dossier; no specific recruitment channels, target-audience details or country-specific approaches are described in the CTIS JSON.

Poland

Earliest CTIS Part Ii Submission Date

03-04-2024

Latest Decision Or Authorization Date

04-08-2025

Processing Time Days

488

Number Of Sites

1

Number Of Participants

180

Primary sponsor

Full Name

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Poland

Third parties

• {"country":"","full_name":"Agencja Badań Medycznych","duties_or_roles":"","organisation_type":""}