A CLINICAL EFFICACY AND SAFETY STUDY TO EVALUATE IN A BLINDED WAY THE NEW MEDICINAL PRODUCT RPC1063 IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
- Conditions
- Moderately to severely active Ulcerative ColitisMedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2012-003123-38-PL
- Lead Sponsor
- Celgene International II Sàrl (CIS II)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 86
1. Males or female patients aged 18 to 75 years, inclusive
2. Have had UC diagnosed at least 3 months prior to screening. The diagnosis of UC must be confirmed by endoscopic and histologic evidence
3. Have active UC confirmed on endoscopy with = 15 cm involvement
4. Have active UC defined as Mayo score of 6-12 inclusive with endoscopic subscore of = 2
5. Have undergone colonoscopy or sigmoidoscopy within the past 2 years for extent of disease, and if the UC has been present for > 10 years, have had a colonoscopy with biopsy to rule out dysplasia
6. . 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
7. Must be currently receiving treatment with at least 1 of the following therapies:
a. Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide) for at least 6 weeks with the dose stable for at least 3 weeks prior to screening endoscopy
b. Prednisone (doses = 30 mg) or equivalent for at least 4 weeks and receiving a stable dose for at least 2 weeks
8. 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
9. All patients aged 45 years or over must have had a colonoscopy to screen for adenomatous polyps within 5 years of their first dose of investigational drug or must have had a colonoscopy at screening to assess for polyps. The adenomatous polyps must be removed prior to their first dose of investigational drug.
10. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments
11.Patients must have documentation of positive Varicella Zoster virus (VZV) IgG antibody status or complete VZV vaccination at least 30 days prior to randomization
12.Documentation of no evidence of chronic lung disease or tuberculosis (TB) on a chest X ray completed within the 6 months prior to screening. If a chest X-ray was not done in the 6 months preceding the Screening visit, it may be performed during the Screening visit
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 85
F.1.3 Elde
1Have severe extensive colitis evidenced by:
Physician judgment that patient is likely to require colectomy or ileostomy within 12 weeks of baseline
Current evidence of fulminant colitis, toxic megacolon or bowel perforation
Previous total colectomy
Have 4 or more of the following:
Temp > 38°C, Heart rate (HR) > 110 (bpm); Focal severe or rebound abdominal tenderness; Anemia (hemoglobin [Hgb] < 8.5 g/dL);Transverse colon diameter > 5cm on plain X-ray
2Diagnosis of Crohn’s disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn’s disease
3Have positive stool culture for pathogens (O+P, bacteria) or positive test for C. difficile at screening. If C. difficile is positive, the patient may be treated and retested
4Have had treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 16 weeks of screening
5Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin (hCG) measured during screening
6Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric or other major systemic disease making implementation or interpretation of the study difficult or that would put the patient at risk
7Clinically 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 QTcF interval (QTcF > 450 msec males, > 470 msec females), or at additional risk for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital long-QT syndrome, concurrent therapy with QT prolonging drugs)
-Patients with other pre-existing stable cardiac conditions who have not been cleared for the study by an appropriate cardiac evaluation by a cardiologist
8Resting HR less than 55 beats per minute (bpm) when taking vitals as part of a physical exam at Screening
9History of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with hemoglobin A1c > 7% , or diabetic patients with significant co-morbid conditions such as retinopathy or nephropathy
10History of uveitis
11Known active bacterial, viral, fungal, mycobacterial infection or other infection (including TB or atypical mycobacterial disease [excluding fungal infection of nail beds]) or any major episode of infection that required hospitalization/treatment with intravenous (IV) antibiotics within 30 days or oral antibiotics within 14 days prior to screening
12History of recurrent or chronic infection (e.g., hepatitis B or C, human immunodeficiency virus [HIV], syphilis, TB); recurring urinary tract infections are allowed
13History of cancer, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved)
14History of alcohol or drug abuse within 1 year prior to randomization
15History of or currently active primary or secondary immunodeficiency
16 History of treatment with a biologic agent within 5 half-lives of that agent prior to randomization
17History of treatment with an investigational agent within 5 half-lives of that agent prior to randomization
18History of treatment with topical rectal steroids within 2 weeks of screening
19.Receipt of a live vaccine or attenuated live vaccine within 4 weeks pri
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Week 8;Main Objective: Compare the efficacy of RPC1063 vs placebo for induction of clinical remission at Week 8 in patients with moderately to severely active UC.;Secondary Objective: - Compare the efficacy of RPC1063 vs placebo at weeks 8 and 32 as measured by clinical response, clinical remission, and mucosal healing<br>- Compare the overall safety and tolerability of RPC1063 vs placebo for the duration of the study;Primary end point(s): Proportion of patients in clinical remission, defined as a Mayo score of = 2 points and with no individual subscore of > 1 point
- Secondary Outcome Measures
Name Time Method