USTEKINUMAB for Crohn's disease

Inclusion criteria

• {"criterion_text":"- Patient has given written informed consent from to participate in the clinical trial."}
• {"criterion_text":"- Patient is male or female aged 18 to 75 years, inclusive."}
• {"criterion_text":"- Patient who has CD, confirmed at any time in the past by radiography, histology, or endoscopy, of at least 3 months prior to the randomization."}
• {"criterion_text":"- Patients with active Crohn's Disease (CD) who have at least moderately active CD, defined by an absolute CDAI score of at least ≥220, despite 12-weeks of treatment with vedolizumab (VEDO)."}
• {"criterion_text":"- The following treatments for CD are allowed: a. azathioprine (AZA), 6-mercaptopurine (6-MP) or methotrexate (MTX), if taken at a stable dose for more than 8 weeks prior to the randomization, b. 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, c. 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, d. 5-Aminosalicylates (5-ASA), if taken at a stable dose for at least 4 weeks prior to the randomization."}
• {"criterion_text":"- 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: •\timplantable progestogen-only hormone contraception associated with inhibition of ovulation; •\tintrauterine device (IUD); •\tintrauterine hormone - releasing system (IUS), •\tbilateral tubal occlusion; •\tpartner 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: •\tprogestogen-only hormone contraception associated with inhibition of ovulation (oral or injectable) •\tcombined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: -\toral -\tintravaginal -\ttransdermal -\tinjectable 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 ustekinumab or any other murine and/or human proteins or has hypersensitivity to immunoglobulin products."}
• {"criterion_text":"- Use of total parenteral nutrition within a month prior to the randomization."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Live or live - attenuated vaccine within 4 weeks prior to the randomization."}
• {"criterion_text":"- Abnormalities in laboratory tests performed at screening: a.\tSerum 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.\tSerum alanine aminotransferase ≥ 2.0 × ULN, c.\tSerum aspartate aminotransferase ≥ 2.0 × ULN, d.\tSerum total bilirubin ≥ 1.5 × ULN, e.\tHemoglobin < 8.5 g/dl (SI units: < 85 g/l or 5.28 mmol/l ), f. \tWhite blood cell count < 3.5 × 103 cells/μl (SI units: <3.5×109 cells/l), g.\tNeutrophil count < 1.5 × 103 cells/μl (SI units: <1.5×109 cells/l), h.\tPlatelet count < 100 × 103 cells/μl (SI units: <100×109 cells/l). i.\tPositive HBsAg result, j.\tPositive HBV DNA result, k.\tPositive HCV RNA result, l.\tPositive anti-HIV result, m.\tPositive or twice inconclusive Quantiferon-TB Gold test result."}
• {"criterion_text":"- Patient who has a current or history of any of the following infections: a.\tKnown 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.\tKnown infection with human immunodeficiency virus (HIV). c.\tAcute infection requiring oral antibiotics within 2 weeks or parenteral injection within 4 weeks prior to the randomization. d.\tRecurrent hemiplegia. e.\tOther recurrent or chronic infection, significant in the investigator’s opinion, within 6 weeks prior to the randomization. f.\tCurrent 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.\tKnown cytomegalovirus infection within 6 months prior to the randomization. h.\tEvidence of Clostridioides difficile toxin in stool within 3 months prior to the randomization. i.\tPatient 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.\tCurrent diagnosis of latent TB at screening (defined as a positive Quantiferon-TB-Gold without clinical signs of active tuberculosis and with a negative examination of chest x-ray from the qualifying visit for vedolizumab treatment). k.\tOther serious infections, in the investigator’s opinion, within 6 months prior to the randomization."}
• {"criterion_text":"- Medical condition including 1 or more of the following a.\tDiagnose of UC (ulcerative colitis) or indeterminate colitis. b.\tShort bowel syndrome. c.\tEvidence of fixed symptomatic stenosis or obstruction of the large or small intestine. d.\tActive entero-vesical, entero-retroperitoneal, entero-cutaneous or entero-vaginal fistulae within 6 months prior to the randomization. Entero-enteral fistulae without clinically significant symptoms in the invesigator’s opinion and anal fistulae without draining problems are allowed. e.\tBody 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."}
• {"criterion_text":"- Current or history of alcohol abuse within 12 months prior to the randomization."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Female patients who are currently pregnant or planning to become pregnant within 6 months of the last dose of study drug."}
• {"criterion_text":"- Female patients who are currently breastfeeding planning to breastfeed within 6 months of the last dose of study drug."}
• {"criterion_text":"- Patient who has received any of following treatments: a.\tWithin 2 weeks prior to randomization: - budesonide taken orally in excess of 9 mg/day, - other GCSs taken orally in excess of 20 mg/day prednisone, - GCSs administered parenterally, - antibiotics for the primary treatment of CD (e.g., ciprofloxacin, metronidazole) b.\tWithin 3 weeks prior to the randomization: - apheresis (e.g., Adacolumn apheresis), c. \tWithin 4 weeks prior to the randomization administration of parenteral antibiotics d.\tWithin 8 weeks prior to the randomization initiation of treatment with the following drugs: - azathioprine, - 6-mercaptopurine, - methotrexate."}
• {"criterion_text":"- Lack of cooperation from the patient."}
• {"criterion_text":"- Patient who has received any of following treatments due to CD or other disease: a. within 4 weeks prior to randomization: janus kinase (JAK) inhibitors, including but not limited to tofacitinib and baricitinib, b. within 8 weeks prior to randomization: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, c. within 12 months prior to randomization: alkylating agents, d. ever: infliximab, ustekinumab."}
• {"criterion_text":"- Currently require or are anticipated to require surgical intervention for CD during the study."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Extensive colonic resection (subtotal and total colectomy) prior to the randomization."}
• {"criterion_text":"- History of more than 3 small-bowel resection procedures."}
• {"criterion_text":"- Stoma (e.g., ileostomy or colostomy) within 6 months prior to the randomization."}
• {"criterion_text":"- Nonautologous stem cell therapy (e.g. Prochymal) within 12 months 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 an absolute CDAI score <150 points.","definition_or_measurement_approach":"Sustained corticosteroid-free remission at week 52, sustained from week 8 onward with a maximum 11-week corticosteroid tapering regimen; clinical remission defined as absolute CDAI score <150 points."}

Secondary endpoints

• {"endpoint_text":"- Percentage of clinical response at Week 8, Week 22 and Week 52, defined as CDAI-100 response,, i.e., a decrease in CDAI score of 100 points or more from the baseline value.","definition_or_measurement_approach":"CDAI-100 response: decrease in CDAI score ≥100 points from baseline measured at Weeks 8, 22, 52."}
• {"endpoint_text":"- Percentage of clinical response at Week 8, Week 22 and Week 52, defined as CDAI-70, i.e. a decrease in CDAI score of 70 points or more form the baseline value.","definition_or_measurement_approach":"CDAI-70 response: decrease in CDAI score ≥70 points from baseline measured at Weeks 8, 22, 52."}
• {"endpoint_text":"- Percentage of clinical remission at Week 8, defined as an absolute CDAI score of < 150 points.","definition_or_measurement_approach":"Clinical remission: absolute CDAI score <150 measured at Week 8."}
• {"endpoint_text":"- Percentage of deaths from Crohn’s disease at Week 8, Week 22 and Week 52. 5. The cumulative dose of corticosteroids used during the current flare of Crohn’s disease at Week 52.","definition_or_measurement_approach":"Occurrence of deaths attributed to Crohn's disease at Weeks 8, 22, 52; cumulative corticosteroid dose during current flare assessed at Week 52."}
• {"endpoint_text":"- The cumulative dose of corticosteroids used during the current flare of Crohn’s disease at Week 52.","definition_or_measurement_approach":"Total cumulative dose of corticosteroids used during the current flare measured at Week 52."}
• {"endpoint_text":"- Percentage of patients who achieved endoscopic remission at Week 8, Week 22 and Week 52 . Endoscopic remission is defined as (all conditions must be met): - SES-CD score ≤ 4 points and - SES-CD score with at least 2 points reduction from baseline value and - SES-CD subscores ≤ 1 point in all individual component.","definition_or_measurement_approach":"Endoscopic remission: SES-CD ≤4 AND ≥2 point reduction from baseline AND all SES-CD subscores ≤1; assessed at Weeks 8, 22, 52."}
• {"endpoint_text":"- Percentage of patients who achieved an endoscopic response at Week 8, Week 22 and Week 52, defined as a 50% reduction in SES-CD score from baseline value.","definition_or_measurement_approach":"Endoscopic response: 50% reduction in SES-CD from baseline measured 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 instruments (SIBDQ, PROMIS-29 v2.1, WPAI:GH v2.2, 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":"Recording of severe adverse events occurrence at Weeks 8, 22, 52."}
• {"endpoint_text":"- Occurrence of non-severe adverse events at Week 8, Week 22 and Week 52.","definition_or_measurement_approach":"Recording of non-severe adverse events occurrence at 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 assessed 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":"MACE events (cardio death, non-fatal MI, non-fatal stroke) occurrence assessed at Weeks 8, 22, 52."}
• {"endpoint_text":"- Occurrence of tuberculosis at Week 8, Week 22 and Week 52.","definition_or_measurement_approach":"Recording of tuberculosis occurrence at Weeks 8, 22, 52."}
• {"endpoint_text":"- Occurrence of hemiplegia at Week 8, Week 22 and Week 52.","definition_or_measurement_approach":"Recording of hemiplegia (shingles/presentation) occurrence at Weeks 8, 22, 52."}

Poland

Earliest CTIS Part Ii Submission Date

29-03-2024

Latest Decision Or Authorization Date

06-05-2024

Processing Time Days

38

Number Of Sites

1

Number Of Participants

192

Primary sponsor

Full Name

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Poland