To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis

Celgene

Status and phase: Active, not recruiting; Phase 3

Conditions: Colitis, Ulcerative

Treatments: Other: Placebo; Drug: Ozanimod

Study type: Interventional

Funder types: Industry

Identifiers

NCT03915769

RPC01-3103

U1111-1230-3228 (Registry Identifier)

Details and patient eligibility

About

Japanese patients with moderate or severe active ulcerative colitis as a subject when ozanimod 0.46 mg or 0.92 mg is orally administered is evaluated about dose response, efficacy and safety with placebo as a control.

Full description

Following the up to 5-week Screening Period, eligible subjects will be randomized to enter the 12 weeks placebo-controlled Induction Period (IP). Subjects who are responders at Week 12 will continue on their assigned treatment in the 40-week Maintenance Period (MP). Non responders at Week 12 have the option to enter the Open-label Extension (OLE). Subjects who complete the MP will be given the option to participate in the OLE. Subjects that enter the MP and experience disease relapse will also have the option to enter the OLE. The OLE will continue until marketing launch (about 4 years of ozanimod for Ulcerative colitis (UC), or until the Sponsor discontinues the development program.

Enrollment: 195 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Main Inclusion Criteria for Induction and Maintenance Periods

1. Subject is a Japanese male or female subjects aged 18 to 75 years at the time of signing the informed consent form (ICF) at Screening.
2. Subject has had Ulcerative Colitis (UC) diagnosed at least 3 months prior to first investigational product administration. The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histopathology report.
3. Subject has evidence of UC extending ≥ 15 cm from the anal verge as determined by Baseline endoscopy (flexible sigmoidoscopy or colonoscopy).
4. Subject has active UC defined as Mayo score of 6 to 12 inclusive, with endoscopic subscore of ≥ 2, a rectal bleeding score of ≥ 1, and a stool frequency score ≥ 1.

Main Inclusion Criteria for Open-label Extension Period

Subjects must satisfy the following criteria to be enrolled in the study:

1. Must have completed the Week 12 Visit and is non-responder at Week 12
2. Who completes the IP and enters the MP, completes participation through the last study treatment visit at Week 52 with maintaining clinical response, OR experiences disease relapse during the MP

Exclusion criteria

Main Exclusion Criteria

1. Subject has severe extensive colitis

2. Subject has diagnosis of Crohn's disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn's disease or microscopic colitis or radiation colitis or ischemic colitis.

3. Subject has positive stool examination for pathogens (ova and parasites, bacteria) or positive test for toxin producing Clostridium difficile (C. difficile) at Screening.4. Subject is pregnant or breastfeeding

4. Subject has clinically relevant cardiovascular conditions

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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195 participants in 3 patient groups, including a placebo group

0.46 mg ozanimod oral capsule once daily (QD)

Experimental group

Description:

It will be a 7-day dose escalation regimen in the IP consisting of 4 days of treatment with 0.23 mg ozanimod, followed by 3 days of treatment with 0.46 mg ozanimod, followed by 0.46 mg ozanimod.

Treatment:

Drug: Ozanimod

0.92 mg ozanimod oral capsule QD

Experimental group

Description:

It will be a 7-day dose escalation regimen in the IP consisting of 4 days of treatment with 0.23 mg ozanimod, followed by 3 days of treatment with 0.46 mg ozanimod, followed by 0.92 mg ozanimod.

Treatment:

Drug: Ozanimod

Placebo oral capsule QD

Placebo Comparator group

Description:

It will be a 7-day dose escalation regimen in the IP consisting of 4 days of treatment with a placebo capsule, followed by 3 days of treatment with two placebo capsules, followed by two placebo capsules.

Treatment:

Other: Placebo