A Study of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease

Overview

About this study

The purpose of this study is to explore the effect of oral ozanimod as an induction treatment for subjects with moderately to severely active Crohn's Disease.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male or female subjects aged 18 to 75 years (at Screening), inclusive.
  • Subject must provide written informed consent prior to any study-related procedures, and have the ability to comply with the Table of Events.
  • Subject has signs and symptoms consistent with a diagnosis of CD for at least 3 months (prior to first IP administration). The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histology report.
    • Note: endoscopy and histopathology confirmation may be obtained during Screening if no prior report is readily available.
  • Subject has met each of the following 2 criteria:
    • a CDAI score ≥ 220 and ≤ 450;
    • an average daily stool frequency ≥ 4 points and/or an abdominal pain of ≥ 2 points.
  • Subject has a SES-CD score of ≥ 6 (or SES-CD ≥4 in subjects with isolated ileal disease).
  • Subject has an inadequate response or loss of response to or is intolerant of at least 1 of the following CD treatments:
    • corticosteroids;
    • immunomodulators;
    • biologic therapy (e.g., ustekinumab, TNFαantagonists, or vedolizumab).
  • If the subject is taking the following background therapies for CD, a stable dose must be maintained as indicated below:
    • oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide) with a stable dose for at least 3 weeks prior to Screening endoscopy;
    • prednisone (doses ≤ 20 mg per day) or equivalent with a stable dose for at least 2 weeks prior to Screening endoscopy;
    • budesonide therapy (doses ≤ 9 mg per day) or beclomethasone doses ≤ 5 mg/day at a stable dose for at least 2 weeks prior to the Screening endoscopy.
  • Subject at high risk (i.e., family history, CD duration) for colonic malignancy has documented evidence of having had a surveillance colonoscopy within the last 2 years or according to local and national medical guidelines to evaluate for polyps, dysplasia, or malignancy. If there is no recent history of surveillance colonoscopy, this can be done as part of the colonoscopy performed during Screening. Any visualized adenomatous polyps must be removed and any suspicious lesion confirmed free of cancer and/or dysplasia prior to randomization.
  • Female subjects of childbearing potential:
  • Must agree to practice a highly effective method of contraception throughout the study until completion of the 75-day Safety Follow-Up Visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl Index of less than 1% per year when used consistently and correctly. Acceptable methods of birth control in the study are the following:
    • combined hormonal (containing oestrogen and progestogen) contraception, which may be oral, intravaginal, or transdermal;
    • progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable;
    • placement of an intrauterine device (IUD);
    • placement of an intrauterine hormone-releasing system (IUS);
    • bilateral tubal occlusion;
    • vasectomised partner;
    • sexual abstinence.
  • Male subjects:
    • Must agree to use a latex condom during sexual contact with women of childbearing potential while participating in the study until completion of the 75-day Safety Follow-up Visit.
  • All subjects:
    • Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
  • Subjects must have documentation of positive varicella zoster virus (VZV) immunoglobulin G (IgG) antibody status or complete VZV vaccination at least 30 days prior to randomization.

Exclusion Criteria:

Exclusions Related to General Health:

  • Subject has any clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric, or other major systemic disease making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study.
  • Subject is likely to require, in the physician's judgment, bowel resection within 12 weeks of entry into the study.
  • Subject has a diagnosis of UC, indeterminate colitis, radiation colitis, or ischemic colitis, or has known strictures or stenosis leading to symptoms of obstruction.
  • Subject has current stoma, ileal-anal pouch anastomosis, symptomatic fistula draining pus that is likely to require, in the physician’s judgement, surgical or medical intervention within 12 weeks of entry into the study, or need for ileostomy or colostomy.
  • Subject has extensive small bowel resection (> 100 cm) or known diagnosis of short bowel syndrome, or subject requires total parenteral nutrition.
  • Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated.
  • Subject has documentation of a positive test for toxin producing Clostridium difficile (C. difficile), or polymerase chain reaction (PCR) examination of the stool on their most recent test, which must have been done in the past 60 days. If positive, subjects may be treated and retested no earlier than 7 days after completion of treatment.
  • Subject has documentation of positive examination for pathogens (ova and parasites, and bacteria), which must have been done in the past 60 days. If positive, subjects may be treated and retested.
  • Subject is pregnant, lactating, or has a positive serum beta human chorionic gonadotropin (β-hCG) measured during Screening.
  • Subject has clinically relevant cardiovascular conditions, making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study, including history or presence of the following:
    • Recent (within the last 6 months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, Class III/IV heart failure, sick sinus syndrome, or severe untreated sleep apnea;
    • Second degree atrioventricular (AV) Block, or third degree heart block unless subjects have a pacemaker in place;
    • Prolonged QT corrected for heart rate using Fridericia's formula (QTcF) interval (QTcF > 450 ms males, > 470 ms females);
    • Resting heart rate (HR) < 55 bpm when taking vitals as part of a physical examination at Screening.
  • Subject has a history of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with hemoglobin A1c (HbA1c) > 9%, or is a diabetic subject with significant comorbid conditions such as retinopathy or nephropathy.
  • Subject has a history of uveitis (within the last year prior to Screening) or clinically confirmed diagnosis of macular edema.
  • Subject has a known active bacterial, viral, fungal, mycobacterial infection, or other infection (including tuberculosis or atypical mycobacterial disease [excluding fungal infection of nail beds, minor upper respiratory tract infections, and minor skin infections]) or any major episode of infection that required hospitalization or treatment with intravenous (IV) antibiotics within 30 days of Screening or oral antibiotics within 14 days of Screening.
  • History or known presence of recurrent or chronic infection (e.g., hepatitis B virus [HBV], hepatitis C virus [HCV], human immunodeficiency virus [HIV]); recurrent urinary tract infections are allowed.
  • Subject has a history of active cancer within 5 years, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin or cervical dysplasia/cancer that have been excised and resolved); or colonic dysplasia that has not been completely removed.
  • Subject has a history of alcohol or drug abuse within 1 year prior to initiation of Screening.

Exclusions Related to Medications:

  • Hypersensitivity to active ingredients or excipients of ozanimod or placebo
  • Subject has a history of primary nonresponse to 2 or more approved biologic therapies used for the treatment of CD.
  • Subject has been treated with a biologic agent within 8 weeks or 5 elimination half-lives (whichever is shorter) prior to the first dose of IP.
  • Subject has a history of treatment with an investigational agent within 5 elimination half-lives of that agent prior to the first dose of IP.
  • Subject has received a live or live attenuated vaccine within 4 weeks prior to the first dose of IP.
  • Subject has received previous treatment with lymphocyte-depleting therapies (eg, Campath®, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, or daclizumab).
  • Subject has received previous treatment with D-penicillamine, leflunomide, or thalidomide.
  • Subject has received previous treatment with natalizumab or fingolimod.
  • Subject has received previous treatment with oral cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 16 weeks of initiation of Screening.
  • Subject has a history of treatment with IV immune globulin (IVIg), or plasmapheresis within 3 months prior to first dose of IP.
  • Subject has discontinued oral or rectal 5-ASA or corticosteroids within 2 weeks prior to the screening endoscopy.
  • Subject has planned concurrent treatment with immunomodulatory agents (e.g., azathioprine, 6-MP, cyclosporine, or methotrexate) after randomization. Subjects receiving azathioprine, 6-MP, or methotrexate at screening must discontinue treatment with these agents prior to first dose of IP.
  • Subject has chronic nonsteroidal anti-inflammatory drug (NSAID) use (note: occasional use of NSAIDs and acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and aspirin up to 325 mg/day is permitted).
  • Subject treated with Class Ia or Class III anti-arrhythmic drugs or with 2 or more agents in combination known to prolong PR interval.
  • Subject receiving treatment with breast cancer resistance protein (BCRP) inhibitors (e.g., cyclosporine, eltrombopag)
  • Subject is receiving treatment with any of the following drugs or interventions within the corresponding timeframe:
    • At randomization:
      • CYP2C8 inhibitors (e.g., gemfibrozil or clopidogrel) and inducers (e.g., rifampicin).
    • Two weeks prior to randomization:
      • o Monoamine oxidase inhibitors (e.g., selegiline, phenelzine).

Exclusions Related to Laboratory Results:

  • Subject has screening ECG results showing any clinically significant abnormality.
  • Subject has serum creatinine results > 1.4 mg/dL for women or > 1.6 mg/dL for men.
  • Subject has liver function impairment or persisting elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) results > 2 times the upper limit of normal (ULN), or direct bilirubin > 1.5 times the ULN.
  • Subject has a platelet count < 100,000/μL.
  • Subject has hemoglobin < 7.5 g/dL.
  • Subject has neutrophils < 1500/μL.
  • Subject has an absolute white blood cell (WBC) count < 3500/μL.
  • Subject has an absolute lymphocyte count (ALC) < 800 cells/μL.
  • Subject has a forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC) < 70% of predicted values at screening.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

La Crosse, Wis.

Mayo Clinic principal investigator

Michael Van Norstrand, M.D., Ph.D.

Open for enrollment

Contact information:

Jodi Kaseno

(608)392-7187

Kaseno.Jodi@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20453730

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