Efficacy and Safety Evaluation of Oral Zasocitinib in Patients with Moderately to Severely Active Crohn's Disease: A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study

Trial statistics

science

3

test molecules

location_city

96

research sites

public

14

countries

medical_information

1

disease

person_search

104

investigators

handshake

15

vendors

Diseases & Conditions

Crohn's disease

Objectives

The primary objective of this study is to evaluate the **efficacy** of orally administered TAK-279, compared to placebo, in achieving endoscopic response at Week 12 in subjects with moderately to severely active Crohn's Disease. This is clinically relevant as endoscopic response is a critical marker of disease activity and can indicate the potential for long-term remission and improved patient outcomes.

Secondary objectives include:

Evaluating the efficacy of TAK-279 in achieving clinical remission, clinical response, and endoscopic remission at Week 12.
Assessing the effect of TAK-279 on patient-reported symptoms over time.
Evaluating the impact of TAK-279 on disease-specific health-related quality of life.

Participants

The clinical trial involves a total of **149 participants** diagnosed with **moderately to severely active Crohn's Disease**. The study population includes both male and female subjects, aged between 18 and 75 years, who are in general good health aside from their Crohn's Disease. Participants were selected based on specific inclusion criteria, including a confirmed diagnosis of Crohn's Disease with a Crohn's Disease Activity Index (CDAI) score between 220 and 450, and the presence of characteristic ulcerations as determined by ileocolonoscopy. The trial does not include a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified, but participants must comply with study procedures and requirements, including the use of digital tools and applications. Key inclusion criteria also require participants to have a history of inadequate response or intolerance to certain therapies for Crohn's Disease. The trial does not specify any exclusion criteria beyond those implied by the inclusion criteria.

Plans and Procedures

The clinical trial is a **randomized**, **double-blind**, placebo-controlled, dose-ranging study designed to evaluate the efficacy and safety of oral **Zasocitinib** in subjects with moderately to severely active **Crohn's disease**. The trial is set to span a total duration of approximately three years, with an estimated recruitment start date in mid-2024 and an anticipated end date in mid-2027. Participants will be involved in the study for a maximum treatment period of 52 weeks. The primary objective is to assess the endoscopic response at Week 12, with secondary endpoints including clinical remission and response, endoscopic remission, and improvements in health-related quality of life.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is determined based on criteria such as age, disease severity, and prior treatment history. Participants must have a documented diagnosis of Crohn's disease and meet specific disease activity scores. Following successful screening, participants will be randomized to receive either Zasocitinib or a placebo. Study visits will occur at regular intervals to monitor efficacy and safety, with assessments including endoscopic evaluations, clinical indices, and patient-reported outcomes. The end-of-study visit will conclude the participant's involvement, with final assessments conducted to evaluate the long-term effects of the treatment.

Participants are expected to comply with all study procedures, including the use of digital tools and applications, and must provide informed consent prior to any study-related activities. Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent. The trial is designed to ensure rigorous evaluation of the investigational product, with all data collected contributing to the understanding of Zasocitinib's potential benefits and risks in treating Crohn's disease.

Treatment

The clinical trial involves the administration of **Zasocitinib**, an investigational medication, to evaluate its efficacy and safety in subjects with moderately to severely active Crohn's Disease. **Zasocitinib** is provided in a **capsule** form and is administered **orally**. The active substance, **Zasocitinib**, is a small molecule with the chemical name N-((1R,2R)-2-methoxycyclobutyl)-7-(methylamino)-5-((2-oxo-2H-[1,2'-bipyridin]-3-yl)amino)pyrazolo[1,5-a]pyrimidine-3-carboxamide. The maximum treatment period for **Zasocitinib** is 52 weeks, although specific dosing schedules and daily dose amounts are not provided in the available data. The medication is developed by Takeda Development Center Americas, Inc.

The study also includes a **placebo** group, which receives a placebo formulation with the same excipients as **TAK-279**. The placebo is used as a comparator to assess the efficacy of **Zasocitinib**. The placebo is also administered in a **capsule** form and taken **orally**. The use of a placebo is essential in maintaining the double-blind nature of the study, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias in the assessment of the treatment's efficacy.

Efficacy

The efficacy of the investigational drug **Zasocitinib** will be assessed in a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study involving subjects with moderately to severely active Crohn's Disease. The primary endpoint for evaluating efficacy is the endoscopic response at Week 12, defined as the proportion of subjects achieving a decrease in the Simple Endoscopic Score for Crohn's Disease (SES-CD) greater than 50% from baseline. For subjects with isolated ileal disease, the criteria are an SES-CD of 4 or less, or at least a 2-point reduction from baseline, with assessments read centrally.

Secondary endpoints include several measures at Week 12: clinical remission, assessed as the proportion of subjects achieving a Crohn's Disease Activity Index (CDAI) of less than 150; clinical response, defined as a reduction in CDAI from baseline of more than 100; and endoscopic remission, assessed as the proportion of subjects achieving an SES-CD of 4 or less, or 2 or less for ileal disease, with no subscore greater than 1. Additional secondary endpoints involve patient-reported outcomes, such as clinical remission in two items of the CDAI, clinical response in PRO2, absence of bowel urgency, and changes in disease-specific health-related quality of life (HRQoL) as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) and fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

The subject is willing and able to understand and fully comply with study procedures and requirements (including digital tools and applications), 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 prior to the initiation of any study procedures.
Subjects must be ≥18 and ≤75 years of age at the time of the signing of the ICF. In South Korea, the age requirement for adult subjects is ≥19 years of age.
Disease-Specific Inclusion Criteria: Subjects must have active moderate to severe ileal (terminal ileum), ileocolonic, or colonic CD at baseline during screening period as defined by: a) CDAI score between 220 and 450 (inclusive) and b) Presence of ulcerations that are characteristic to CD, as determined by ileocolonoscopy performed during screening, and as defined by the SES-CD ≥6 (SES-CD ≥4 for isolated ileitis)
Disease-Specific Inclusion Criteria: Subjects must have a documented diagnosis (endoscopic with histology) of CD for at least 30 days before screening. Documented diagnosis is defined as: a) A biopsy report to confirm the histological diagnosis AND b) A report documenting disease duration based upon prior ileocolonoscopy. 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 ileocolonoscopy should be consistent with a CD diagnosis. If the histology diagnosis is not clear and the endoscopy is inconsistent with CD at this time point, the subject will not be randomized.
Disease-Specific Inclusion Criteria: Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, aged >50 years, or other known risk factors must be up to date on colorectal cancer surveillance (may be performed during screening).
Disease-Specific Inclusion Criteria: Subjects must be willing and able to undergo ileocolonoscopy with biopsies during screening after all other inclusion criteria have been met.
Prior Treatment Failure Criteria: 7. Subjects with a history of inadequate response to, loss of response to, or intolerance to one or more of these therapies for CD based on Physician assessment: (according to either (a) or (b) below or a combination of both) (Details provided in Appendix 2).: a) 6-mercaptopurine or azathioprine, oral or IV corticosteroids or history of corticosteroid dependence (an inability to successfully taper corticosteroids without return of CD 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 JAKi or S1P receptor modulators).
Other General Inclusion Criteria: 8. Subjects are (CCI). For individuals of reproductive potential, if sexually active, agree to comply with the contraceptive requirements for the duration of the study and 10 days after the last dose of the study drug. The following birth control requirements must be met: b) Female (sex-assigned at birth) subjects must be surgically sterile or be of nonchildbearing potential with confirmation of postmenopausal status (ie, follicle-stimulating hormone level >40 mIU/mL); or, if sexually active with a nonsterilized individual who produces sperm agrees to use a highly effective method of contraception from the signing of informed consent throughout the duration of the study

cancel

Exclusion Criteria

Exclusion Criteria Related to GI Tract: Subjects with IBD indeterminate or unclassified, microscopic colitis, ischemic colitis, infectious colitis, or radiation colitis, and diverticular disease associated with colitis, and/or clinical/histologic findings suggestive of ulcerative colitis.
Exclusion Criteria Related to GI Tract: Have complications of CD such as strictures, stenoses, short gut syndrome, or any other manifestation that might require surgery during the study, could preclude the use of the CDAI/PRO2 to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with TAK-279.
Exclusion Criteria Related to GI Tract: Have any current or prior abscesses unless they have been drained and treated at least 6 weeks prior to randomization and are not anticipated to require surgery during the treatment period. Subjects with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present.
Exclusion Criteria Related to GI Tract: Subjects with presence of enterovesical (ie, between the bowel and urinary bladder) or enterovaginal fistulae.
Exclusion Criteria Related to GI Tract: Have had any kind of bowel resection or diversion within 6 months or any other intraabdominal surgery within 3 months prior to screening. Subjects with >2 bowel resections, subtotal colectomy, or proctocolectomy are excluded. Subjects who have had limited surgery for CD may be allowed in the study, provided that this does not affect efficacy assessment. Discussion with the sponsor medical team should occur prior to screening.
Exclusion Criteria Related to GI Tract: Subjects with a current ileostomy or colostomy. Subjects who had a j-pouch are excluded as a j-pouch could result in a stoma.
Exclusion Criteria Related to GI Tract: Subjects with obstructive/ symptomatic colonic stricture may require surgery for CD during treatment period.
Exclusion Criteria Related to GI Tract: Subjects with past medical history or presence of toxic megacolon.
Exclusion Criteria Related to GI Tract: Subjects with gastrointestinal dysplasia or neoplasia except history of adenomatous polyps that have been completely removed.
Exclusion Criteria Related to GI Tract: Subjects with evidence or suspicion of liver disease or primary sclerosing cholangitis.
Exclusion Criteria related to Medication:
Exclusion Criteria Related to Other Prohibited Concomitant Medications: Subjects on CD-related antibiotics who have not been on stable doses for greater than or discontinued within 14 days prior to the first administration of study drug.
Exclusion Criteria Related to Other Prohibited Concomitant Medications: Subjects on oral 5-ASAs who have not been on stable doses for greater than, or discontinued within, at least 14 days prior to the first administration of study drug or receiving mesalamine >4.8g/day (or equivalent).
Subjects on high dose corticosteriods
Subjects on prohibited medications as listed in the protocol
Exclusion Criteria related to Infectious Diseases: Tuberculosis (TB): a) Subject has current active TB infection, regardless of treatment status. b) Subject who has positive QuantiFERON will require to start treatment for latent TB at least 2 weeks prior to randomization. c) Subject has a positive QuantiFERON-TB Gold (QFT) or T-Spot, TB skin test (TST) result or 2 indeterminate QFT or TST results. TST is considered positive if 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 based on local guidelines a minimum of 2 weeks prior to 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 or TST may be used based on country and site-specific guidelines. d) Subject has had any imaging study during or 6 months prior to screening, including x-ray, chest computed tomography, magnetic resonance imaging, or other chest imaging suggesting evidence of current active of TB.
Exclusion Criteria related to Infectious Diseases: Herpes infections: a) Subject has active herpes virus infection, including herpes zoster or herpes simplex 1 and 2 (demonstrated on physical examination and/or medical history) at screening or prior to the first administration of study drug, b) Subject has a history of herpetic infection within 8 weeks prior to screening. c) Subject has 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).
Non-herpetic 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.
Other infectious diseases: a) Subject has history of symptoms suggestive of systemic or invasive infection within 30 days prior to the first administration of study drug. b) Subject has history of bacterial, viral, or fungal infection that required hospitalization or treatment with intravenous antimicrobial therapy within 8 weeks prior to the first administration of study drug, or oral antimicrobial therapy within 30 days prior to the first administration of study drug. c)Subject 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) Subject has a history of an infected joint prosthesis unless that prosthesis has been removed or replaced within 60 days prior to the first administration of study drug. e) Subject has a history of opportunistic infections (eg, Pneumocystis jirovecii pneumonia, histoplasmosis, coccidiomycosis). f) Subjects 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 prior to the first administration of study drug. g) Subject has active CMV colitis requiring treatment in last 2 weeks prior to the first administration of study drug.
Exclusion Criteria related to Health: Noninfectious Disorders Exclusions: 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) Subject has a history of known or suspected condition/illness that is consistent with compromised immunity, including but not limited to any identified congenital or acquired immunodeficiency, splenectomy. b) Subject had a major surgery within 60 days prior to the first administration of study drug or has a major surgery planned during the study. c) Subject 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) Subject has a history of Class III or IV congestive heart failure as defined by New York Heart Association criteria. e) Subject has a history of cancer or lymphoproliferative disease within 5 years prior to 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 based on this exclusion criterion. f) For 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 corticosteroids treatment, or has required more than one course of oral corticosteroids within 6 months prior to the first administration of study drug. g) Subject has any of the following cardiovascular history or unstable cardiovascular disease: •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. •Any history of cerebrovascular event, myocardial infarction, coronary stenting, or aorto-coronary bypass surgery within the past 6 months prior to screening. h) Subject has ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the subject if they participate in the study, in the opinion of the investigator. i) Subject has history of any significant/uncontrolled psychiatric illness (including but not limited to active suicidal ideation at screening or prior to 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) Subject 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.
Exclusion Criteria related to Laboratory Investigations: Subject has inadequate renal or hepatic function before randomization based on the following parameters: a) Total bilirubin (unconjugated and/or conjugated) ≥1.5 × ULN unless the subject has known Gilbert’s syndrome that can explain the elevation of bilirubin, or b) Serum ALT or AST ≥3 × ULN, or c)Creatinine >1.5 × ULN. –Note: The subjects may be retested (1 time) to meet eligibility criteria at the discretion of the investigator. d) Estimated creatinine clearance <45 mL/min based on the Cockcroft-Gault calculation.
Exclusion Criteria related to Laboratory Investigations: 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 g) Thyroid-stimulating hormone (TSH), free T4 (thyroxine) or T3 (triiodothyronine) outside the normal reference range. h) Subject has 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.
Other General Exclusion Criteria: Subject does not tolerate venipuncture or inability to be venipunctured.
Allergies and Adverse Drug Reactions Exclusions: a) Subject has history of significant drug allergy (such as anaphylaxis). b) Subject has a known or suspected intolerance, hypersensitivity, or allergy to TAK-279 or any of its components, as follows:
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.
Subjects who have given greater than 500 mL of blood or plasma within 30 days of screening (during a clinical trial or at a blood bank donation) or plans to donate blood during the study.
Subject is compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Subject is a study site employee, an immediate family member (eg, spouse, parent, child, sibling), or is in a dependent relationship with a study site employee who is involved in conduct of this study or may consent under duress.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Recruiting	15 Jul 2024	8
Bulgaria	Recruiting	15 Jul 2024	8
Czechia	Recruiting	15 Jul 2024	6
Denmark	Recruiting	15 Jul 2024	9
France	Recruiting	15 Jul 2024	10
Germany	Recruiting	15 Jul 2024	13
Greece	Recruiting	15 Jul 2024	8
Hungary	Recruiting	15 Jul 2024	6
Italy	Recruiting	15 Jul 2024	11
The Netherlands	Recruiting	15 Jul 2024	—