A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Oral RPC1063 as Induction and Maintenance Therapy for Moderate to Severe Ulcerative Colitis

Phase 3

Completed

Conditions: chronic inflammation of the mucous membrane of the large intestine
inflammatory bowel disease
10017969

Registration Number: NL-OMON47446

Lead Sponsor: Celgene International II Sarl (CIS II)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 33

Inclusion Criteria

1. Male or female patients aged 18 to 75 years (at screening), inclusive
2. Have had UC diagnosed at least 3 months prior to first investigational drug administration. The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histopathology report (note: endoscopy and histopathology may be performed at Screening if no prior report is readily available).
3. Evidence of UC extending * 15 cm from the anal verge as determined by Baseline
endoscopy (flexible sigmoidoscopy or colonoscopy)
4. Have 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
5. Must be currently receiving treatment with at least 1 of the following therapies and
must continue on these therapies during Induction:
* - Oral aminosalicylates at a therapeutic dose for their disease (eg, mesalamine,
sulfasalazine, olsalazine, balsalazide), with the dose stable for at least 3 weeks,
prior to Screening endoscopy
* - Prednisone (doses * 20 mg per day) or equivalent receiving a stable dose for at
least 2 weeks prior to Screening endoscopy
* - Budesonide MMX therapy receiving a stable dose for at least 2 weeks prior to screening endoscopy.
6. Have undergone colonoscopy (or are willing to undergo colonoscopy during Screening):
- within the past 2 years, to screen for dysplasia (unless otherwise recommended by local and national guidelines) if the patient has had left-sided colitis of > 12 years duration or total / extensive colitis of > 8 years duration
- within the past 5 years, to screen for polyps if the patient age is > 45 years
7. If oral aminosalicylates or corticosteroids have been recently discontinued, they must
have been stopped for at least 2 weeks prior to the endoscopy used for Baseline Mayo
Score
8. Female patients of childbearing potential:
Must agree to practice a highly effective method of contraception throughout the trial 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 trial are the following:
-combined hormonal (oestrogen and progestogen containing) 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 patients:
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 patients:
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.
9. Must provide written informed consent and have the ability to be compliant with the schedule of protocol assessments
10. Patients must have documentation of positive Varicella zoster virus IgG antib

Exclusion Criteria

1. Have severe extensive colitis as evidenced by:
* Physician judgment that the patient is likely to require colectomy or ileostomy
within 12 weeks of Baseline
* Current or recent (within 3 months) evidence of fulminant colitis, toxic
megacolon, or bowel perforation
2. 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. Have positive stool examination for pathogens (ova and parasites, bacteria) or
positive test for toxin producing Clostridium difficile (C. difficile) at Screening. PCR (polymerase chain reaction) examination of the stool for C. difficile may be used to excude false positives. If positive, patients may be treated and retested. Documentation of a negative test result for pathogens (ova and parisites, bacteria) is required within 60 days of Day 1.
4. Pregnancy, lactation, or a positive serum *-human chorionic gonadotropin (*-hCG) measured during Screning
5. Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine,
psychiatric, or other major systemic disease making implementation of the protocol or
interpretation of the trial difficult or that would put the patient at risk by participating
in the trial
6. Clinically relevant cardiovascular conditions, including history or presence of:
* 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
* Prolonged Fridericia's corrected QT interval (QTcF; QTcF > 450 msec
for males, > 470 msec for females), or at additional risk for QT interval
prolongation (eg, hypokalemia, hypomagnesemia, congenital long-QT
syndrome)
* Resting HR < bpm when taking vital signs as part of a physical exam at
Screening
7. History of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with
glycosylated Hb (HbA1c) > 9% , or diabetic patients with significant comorbid
conditions such as retinopathy or nephropathy
8. History of uveitis (within the last year) or macular edema
9. Known active bacterial, viral, fungal, mycobacterial infection, or other infection
(including tuberculosis or atypical mycobacterial disease [but 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 antibiotics within 30 days of Screening or oral antibiotics
within 14 days of Screening
10. History of cancer, including solid tumors and hematological malignancies (except
basal cell and in situ squamous cell carcinomas of the skin or uterine cervix that have
been excised and resolved) or colonic mucosal dysplasia
11. History of alcohol or drug abuse within 1 year prior to randomization;Exclusions Related to Medications:;12. History of treatment with a biologic agent within 8 weeks or 5 elimination half-lives (whichever is less) of that agent prior to randomization
13. History of treatment with an investigational agent within 5 elimination half-lives of
that agent prior to randomization
14. History of treatment with topical rectal 5-aminosalicyli