ZASOCITINIB for Moderately to severely active ulcerative colitis | Ulcerative colitis

Inclusion criteria

• {"criterion_text":"- The subject is willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator. The subject has provided informed consent (that is, in writing, documented via a signed and dated ICF) and any required privacy authorization before the initiation of any study procedures.\n- Subjects must be aged ≥18 and ≤75 years at the time of the signing of the ICF.\n- Subjects must have moderately to severely active UC at screening as defined by: a. A modified Mayo score of 5 to 9 points, with b. An endoscopic subscore of ≥2.\n- Subjects must have a documented diagnosis (endoscopic with histology) of UC for at least 30 days before screening with disease extending >15 cm from the anal verge. Documented diagnosis is defined as: a. A biopsy report to confirm the histological diagnosis AND b. A report documenting disease duration based upon prior colonoscopy. Note: If a biopsy report is not available in the source document at the time of screening, a local histology report of a biopsy performed during the screening colonoscopy should be consistent with a UC diagnosis. If the histology diagnosis is not consistent with UC at this time point, the subject will not be eligible for inclusion.\n- Subjects with extensive colitis or pancolitis of >8 years’ duration or left-sided colitis >12 years’ duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (if not performed in the previous 12 months, it must be performed during screening).\n- Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factors must be up to date on colorectal cancer surveillance (may be performed during screening).\n- Subjects must be willing and able to undergo colonoscopy with biopsies during screening after all other inclusion criteria have been met.\n- Subjects with a history of inadequate response to, loss of response to, or intolerance to one or more of these therapies for UC based on Physician assessment (according to either [a] or [b] below or a combination of both): a) 6-mercaptopurine or azathioprine, oral or IV corticosteroids, or history of corticosteroid dependence (an inability to successfully taper corticosteroids without return of UC symptoms), oral 5-ASAs. AND/OR b) Biologic agents (such as TNF antagonists, antibodies to IL-23p19, IL-12/23p40, vedolizumab) or any advanced therapy (such as α4 integrin antagonists, JAKi, or S1P receptor modulators). • Inadequate response: The subject experiences continued disease activity despite treatment with an adequate therapeutic dose and treatment course (dictated by the product label and UC therapeutic guidelines as per the study site region). • Loss of response: The subject experiences relapse after an initial clinical response or remission. • Intolerance: The subject has a history of having experienced an unacceptable or dose-limiting toxicity associated with the use of the agent.\n- Subjects are of nonchildbearing potential. for individuals of reproductive potential, if sexually active, agree to comply with the contraceptive requirements of the protocol. The following birth control requirements must be met: Female (sex-assigned at birth) subjects must be surgically sterile; or be of nonchildbearing potential with confirmation of postmenopausal status (ie, follicle-stimulating hormone levels>40 mIU/mL); or, if sexually active with a nonsterilized individual who produces sperm, agree to use a highly effective method of contraception from the signing of the ICF throughout the duration of the study."}

Exclusion criteria

• {"criterion_text":"- 1. Subjects with indeterminate/unclassified inflammatory bowel disease, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, diverticular disease associated with colitis, and/or clinical/histologic findings suggestive of CD.\n- 18.\tOther infectious diseases: a.\tSubject has history of symptoms suggestive of systemic or invasive infection within 30 days before the first administration of study drug. b.\tSubject has a history of bacterial, viral, or fungal infection that required hospitalization or treatment with intravenous antimicrobial therapy within 8 weeks before the first administration of study drug or oral antimicrobial therapy within 30 days before the first administration of study drug. c.\tSubject has a history of chronic or recurrent bacterial disease, including but not limited to chronic pyelonephritis or cystitis, chronic bronchitis/pneumonitis, osteomyelitis, or chronic skin ulcerations/infections or fungal infections (except superficial onychomycosis). d.\tSubject has a history of an infected joint prosthesis unless that prosthesis has been removed or replaced within 60 days before the first administration of study drug. e.\tSubject has a history of opportunistic infections (eg, Pneumocystis jirovecii pneumonia, histoplasmosis, coccidiomycosis). f.\tSubjects with active enteric infections (positive stool culture and sensitivity), intestinal pathogens, Clostridioides difficile infection, or pseudomembranous colitis (subjects with infection at screening may be allowed retest after treatment) within 4 weeks before the first administration of study drug. g.\tSubject has active cytomegalovirus colitis requiring treatment in last 2 weeks before the first administration of study drug.\n- 19.\tNoninfectious disorders: Subject has any clinically significant medical condition, evidence of an unstable clinical condition (eg, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or immunologic), or vital signs/physical/laboratory/ECG abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results. These include but are not limited to: a.\tSubject has a known or suspected history of a condition/illness that is consistent with compromised immunity, including but not limited to any identified congenital or acquired immunodeficiency or splenectomy. b.\tSubject had a major surgery within 60 days before the first administration of study drug or has a major surgery planned during the study. c.\tSubject has uncontrolled hypertension characterized by systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg at screening, confirmed by 2 separate visits. d.\tSubject has a history of Class III or IV congestive heart failure as defined by New York Heart Association criteria. e.\tSubject has a history of cancer or lymphoproliferative disease within 5 years before the first administration of study drug. Note: Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded on the basis of this exclusion criterion. f.\tFor subjects with asthma, chronic obstructive pulmonary disease, or other pulmonary illnesses, subject has been hospitalized in the past 3 months, has ever required intubation for treatment, currently requires oral corticosteroid treatment, or has required more than 1 course of oral corticosteroids within 6 months before the first administration of study drug. g. Subject has any of the following cardiovascular history or unstable cardiovascular disease: A. A new diagnosis of atrial fibrillation, or an episode of atrial fibrillation with rapid ventricular response or other dysrhythmia), non-acute cardiac hospitalization (eg, pacemaker implantation) pulmonary embolism, or deep venous thrombosis within the past 6 months prior to screening. B. Any history of cerebrovascular event, myocardial infarction, coronary stenting, or aorto-coronary bypass surgery within the past 6 months prior to screening. h.\tSubject has ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the subject if he or she participated in the study, in the opinion of the investigator. i.\tSubject has history of any significant/uncontrolled psychiatric illness (including but not limited to active suicidal ideation at screening or before the first administration of study drug) for which participation in the trial would, in the opinion of the investigator, put the subject at undue risk or would interfere with interpretation of study results. j.\tSubject has a known history of clinically significant drug or alcohol abuse within 12 months prior to the first administration of study drug as determined by the investigator.\n- 2. Subjects with complications of UC such as strictures, stenoses, fistulas, short gut syndrome, or any other manifestation that might require surgery during the study, could preclude the use of the modified Mayo score to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with TAK-279.\n- 20. Subject has inadequate renal or hepatic function before randomization based on the following parameters: a.\tTotal bilirubin (unconjugated and/or conjugated) ≥1.5 × upper limit of normal (ULN) unless the subject has known Gilbert’s syndrome that can explain the elevation of bilirubin, or b.\tSerum ALT or AST ≥3 × ULN, or c.\tCreatinine >1.5 × ULN. Note: The subjects may be retested (1 time) to meet eligibility criteria at the discretion of the investigator. d.\td.\tEstimated creatinine clearance <45 mL/min based on the Cockcroft-Gault calculation.\n- 21. Subject with any of the following laboratory values at the screening visit: a. Hemoglobin <9.0 g/Dl (<90.0 g/L). b. Absolute white blood cell count <3.0 × 109 /L (<3000/mm3 ). c. Absolute neutrophil count of <1.2 × 109 /L (<1200/mm3 ). d. Absolute lymphocyte count of <0.75 × 109 /L (<750/mm3 ). e. Platelet count <100 × 109 /L. f. g. Thyroid-stimulating hormone (TSH) outside the normal reference range and free T4 (thyroxine) or T3 (triiodothyronine) outside the normal reference range. h. Any other significant laboratory abnormalities that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study. i. CPK > ULN. CPK may be repeated once; if repeat value is CTCAE Grade 1 or lower (or ≤2.5 × ULN) and no higher than the initial value, subject remains eligible. Investigators should assess the subject for modulating factors including concomitant medications or vigorous exercise that may affect CPK levels.\n- 22. The subject does not tolerate venipuncture or is unable to be venipunctured.\n- 23. Allergies and adverse drug reactions exclusions: a.\tSubject has a history of significant drug allergy (such as anaphylaxis). b.\tSubject has a known or suspected intolerance, hypersensitivity, or allergy to TAK-279 or any of its components.\n- 24. Subject has a positive pregnancy test result or plans to become pregnant or donate sperm during the study period, or subject is pregnant or lactating/nursing.\n- 3. Subjects with any current or prior abscesses unless they have been drained and treated at least 6 weeks before randomization and are not anticipated to require surgery during the treatment period.\n- 4. Subjects who have had extensive surgery for UC, including subtotal colectomy or proctocolectomy or have bowel surgery planned during the study. Subjects who have had limited surgery for UC (for example, segmental colonic resection) may be allowed in the study, provided that this does not affect efficacy assessment. Discussion with the sponsor medical team should occur before screening.\n- 10.\n- 5. Subjects with any kind of small bowel or colonic surgery within 6 months or any other intra-abdominal surgery within 3 months before screening. Subjects with >2 bowel resections are excluded.\n- 6. Subjects with a current ileostomy or colostomy. Subjects who had a J-pouch are excluded, as a J-pouch could result in a stoma.\n- 7. Subjects with past medical history or presence of toxic megacolon, intra-abdominal abscess, or stricture/stenosis with the small bowel or colon.\n- 8. Subjects with gastrointestinal dysplasia or neoplasia, except history of adenomatous polyps that have been completely removed.\n- 9. Subjects with evidence of or suspected liver disease or primary sclerosing cholangitis.\n- 25. Subjects who have given greater than 500 mL of blood or plasma within 30 days of screening (during a clinical trial or a blood bank donation) or plans to donate blood during the study.\n- 26. Subject is compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.\n- 27. Subject is sponsor or site personnel involved in the clinical study or their immediate family.\n- 11. Subjects on UC-related antibiotics who have not been on stable doses for greater than, or discontinued within, 14 days before the first administration of study drug.\n- 12. Subjects on oral 5-ASAs who have not been on stable doses for greater than, or discontinued within, at least 14 days before the first administration of study drug or receiving mesalamine >4.8 g/day (or equivalent).\n- 13.\n- 14.\n- 15. Tuberculosis (TB): a.\tSubject has current active TB infection, regardless of treatment status. b.\tSubject who has a positive QuantiFERON test result will be required to start treatment for latent TB at least 2 weeks before randomization. c.\tSubject has a positive QuantiFERON-TB Gold (QFT) or T-Spot TB test (TBT) result or 2 indeterminate QFT or TBT results, or tuberculin skin test (TST) reaction ≥10 mm, unless there are no signs/symptoms of active TB and documentation of prior and complete treatment for latent TB (appropriate in duration and type according to current local country guidelines) has been completed or subject has initiated prophylaxis on the basis of local guidelines for a minimum of 2 weeks before the first administration of study drug and documentation of no history of active TB can be provided. Note: TB prophylaxis regimens should be administered according to local guidelines. However, because of potential interactions with TAK-279, rifampin should not be used. Note: QFT, TBT, or TST may be used on the basis of country and site-specific guidelines. d.\tSubject has had any imaging study during or 6 months before screening, including x-ray, chest computed tomography, magnetic resonance imaging, or other chest imaging, suggesting evidence of active TB.\n- 16. Herpes infections: a.\tSubject has active herpes virus infection, including herpes zoster or herpes simplex 1 and 2 (demonstrated on physical examination and/or medical history) at screening before the first administration of study drug. b.\tSubject has a history of herpetic infection within 8 weeks before screening. c.\tSubject has a history of serious herpetic infection that includes any episode of disseminated disease, multidermatomal herpes simplex virus, herpes encephalitis, ophthalmic herpes, or recurrent herpes zoster (defined as 2 episodes within 2 years).\n- 17. Nonherpetic viral diseases: a. Subject has presence of hepatitis C virus (HCV) antibody and a positive confirmatory test result for HCV RNA (nucleic acid test or polymerase chain reaction). b. Subject has presence of positive hepatitis B surface antigen (HBsAg+), presence of hepatitis B virus DNA, or positive anti-hepatitis B core antibody without concurrent positive hepatitis B surface antibody (HBcAb+ and HBsAb-). c. Subject has positive results for HIV by serology, regardless of viral load."}

Primary endpoints

• {"endpoint_text":"- Clinical remission at Week 12, assessed as the proportion of subjects achieving a modified Mayo score of ≤2 with stool frequency subscore of ≤1, rectal bleeding subscore of 0, and centrally read endoscopic subscore of ≤1 (score of 1 modified to exclude friability).","definition_or_measurement_approach":"Clinical remission defined as modified Mayo score ≤2 with stool frequency subscore ≤1, rectal bleeding subscore 0, and centrally read endoscopic subscore ≤1 (endoscopic score of 1 modified to exclude friability); assessed at Week 12; proportion of subjects meeting these criteria."}

Secondary endpoints

• {"endpoint_text":"- Clinical response at Week 12, assessed as the proportion of subjects achieving a reduction from baseline in modified Mayo score of ≥2 points and ≥30% from baseline and a decrease from baseline in the rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of ≤1 point.\n- Symptomatic remission at Week 12, assessed as the proportion of subjects achieving a rectal bleeding subscore of 0 and stool frequency subscore of ≤1.\n- Endoscopic improvement at Week 12, assessed as the proportion of subjects achieving a modified Mayo endoscopic subscore of ≤1 (score of 1 modified to exclude friability).\n- Endoscopic remission at Week 12, assessed as the proportion of subjects achieving a modified Mayo endoscopic subscore of 0.\n- Proportion of subjects with no bowel urgency as measured by the bowel urgency electronic diary (eDiary) item at Week 12.\n- Proportion of subjects with no abdominal pain as measured by the abdominal pain eDiary item at Week 12.\n- Disease-specific HRQoL as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 12, assessed as the proportion of subjects with total score ≥170.\n- Change from baseline in disease-specific HRQoL as measured by the IBDQ total score at Week 12.\n- Change from baseline in fatigue as measured by the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-Fatigue) score at Week 12.","definition_or_measurement_approach":"Endpoints measured at Week 12 using modified Mayo score components (clinical response/remission/endoscopic subscores), centrally read endoscopy for endoscopic subscores, patient-reported eDiary items for bowel urgency and abdominal pain, IBDQ total score for HRQoL (proportion ≥170 and change from baseline), and FACIT-Fatigue total score for fatigue change from baseline."}

Methods

• Digital advertising: Program Digital Ads, Program Search Ads (online search advertising), social media video scripts and digital assets (Program Social Media Video Script series) used to reach patients online.
• Study website and landing pages: Program Website Copy and Study Landing Pages to provide study information and pre-screening.
• Patient-facing emails and messaging: Advocacy Email, Doctor to Patient Email, Program Patient Messaging and patient email communications to inform potential participants and advocacy contacts.
• Printed materials and in-clinic materials: Recruitment brochures, recruitment posters, appointment reminder cards, study brochures and subject participation cards for site-based recruitment.
• Pre-screening and e-screen tools: Trialbee self-assessment and secondary assessment tools, master screener forms and electronic pre-screen activities.
• Advocacy outreach: Advocacy letters and advocacy messaging to patient advocacy organizations and groups to facilitate recruitment.
• Third-party/agency recruitment and site support: Use of CROs and patient recruitment vendors (e.g., Clinical Trial Media, WCG Clinical, Scout Clinical, Trialbee) to manage digital campaigns, patient outreach and site support.

Slovakia

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

507

Number Of Sites

5

Number Of Participants

8

Greece

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

574

Number Of Sites

5

Number Of Participants

8

Belgium

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

14-11-2025

Processing Time Days

493

Number Of Sites

2

Number Of Participants

3

Czechia

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

01-12-2025

Processing Time Days

525

Number Of Sites

11

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

14-11-2025

Processing Time Days

508

Number Of Sites

6

Number Of Participants

10

Romania

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

24-11-2025

Processing Time Days

585

Number Of Sites

7

Number Of Participants

7

Bulgaria

Earliest CTIS Part Ii Submission Date

28-05-2025

Latest Decision Or Authorization Date

14-11-2025

Processing Time Days

170

Number Of Sites

6

Number Of Participants

8

France

Earliest CTIS Part Ii Submission Date

21-06-2024

Latest Decision Or Authorization Date

02-04-2026

Processing Time Days

650

Number Of Sites

3

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

10-07-2024

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

658

Number Of Sites

5

Number Of Participants

9

Poland

Earliest CTIS Part Ii Submission Date

10-07-2024

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

652

Number Of Sites

13

Number Of Participants

105

Norway

Earliest CTIS Part Ii Submission Date

21-06-2024

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

655

Number Of Sites

2

Number Of Participants

9

Denmark

Earliest CTIS Part Ii Submission Date

10-07-2024

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

658

Number Of Sites

6

Number Of Participants

10

Hungary

Earliest CTIS Part Ii Submission Date

12-07-2024

Latest Decision Or Authorization Date

06-05-2026

Processing Time Days

663

Number Of Sites

6

Number Of Participants

8

Primary sponsor

Full Name

Takeda Development Center Americas Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

CRO

Name

PRA Hellas CRO A.E.

Responsibilities

Study start up, contract negotiation and monitoring activities in Greece

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"CRO","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clinical Trial Media Inc.","duties_or_roles":"Patient Recruitment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"Laboratory services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"IQVIA Laboratories","duties_or_roles":"Laboratory services","organisation_type":"Health care"}
• {"country":"United States","full_name":"Rules Based Medicine Inc.","duties_or_roles":"Laboratory services","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Patient Recruitment, Staffing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"Site services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"DMC, statistical/adjudication services","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Canada","full_name":"Alimentiv Inc.","duties_or_roles":"Imaging Services","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"PRA Hellas CRO A.E.","duties_or_roles":"Study start up, contract negotiation and monitoring activities in Greece","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement/Stipend","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"Laboratory services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central ECG Collection/MACE adjudication","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Electronic data capture / ePRO / rater training","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Laboratories (UK address)","duties_or_roles":"Laboratory services","organisation_type":"Health care"}
• {"country":"United States","full_name":"Eurofins Viracor Biopharma Services LLC","duties_or_roles":"Laboratory services","organisation_type":"Laboratory/Research/Testing facility"}