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

• Register: EUCTR
• Last refreshed on: 25 May 2020
• Main ID: EUCTR2012-003123-38-PL
• Date of registration: 15/01/2013
• Prospective Registration: Yes
• Primary sponsor: Celgene International II Sàrl (CIS II)
• Public title: 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
• Scientific title: A PHASE 2, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PARALLEL-GROUP STUDY TO EVALUATE THE CLINICAL EFFICACY AND SAFETY OF INDUCTION THERAPY WITH RPC1063 IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
• Date of first enrolment: 10/02/2013
• Target sample size: 86
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003123-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Optional open-label treatment period; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bulgaria, Czech Republic, Greece, Hungary, Israel, Korea, Republic of, Netherlands, Poland, Russian Federation, Slovakia, Ukraine, United States

Contacts

• Name: PPD Project Manager
• Affiliation: PPD

• Name: PPD Project Manager
• Affiliation: PPD

Key inclusion & exclusion criteria

Inclusion criteria:
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
Exclusion criteria:
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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderately to severely active Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: 0.25 mg RPC1063
Pharmaceutical Form: Capsule
INN or Proposed INN: RPC1063
Current Sponsor code: RPC1063
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: 0.5 mg RPC1063
Pharmaceutical Form: Capsule
INN or Proposed INN: RPC1063
Current Sponsor code: RPC1063
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: 1 mg RPC1063
Pharmaceutical Form: Capsule
INN or Proposed INN: RPC1063
Current Sponsor code: RPC1063
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: Week 8

Secondary Objective: - Compare the efficacy of RPC1063 vs placebo at weeks 8 and 32 as measured by clinical response, clinical remission, and mucosal healing
- 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(s)

Timepoint(s) of evaluation of this end point: See section E.5.2

Secondary end point(s): Efficacy Endpoints:

• Proportion of patients with a clinical response at Week 8, defined as a reduction from baseline in Mayo score of = 3 points and = 30%, and a decrease from baseline in the rectal bleeding subscore of = 1 point or an absolute rectal bleeding subscore of = 1 point
• Change from baseline in Mayo score at Week 8
• Proportion of patients with mucosal healing at Week 8, defined by an endoscopy subscore of = 1 point
Proportion of patients in clinical remission at Week 32 defined as Mayo score of = 2 points with no individual subscore of > 1 point
• Proportion of patients with a clinical response at Week 32, defined as a reduction from baseline in Mayo score of = 3 points and = 30%, and a decrease from baseline in the rectal bleeding subscore of = 1 point or an absolute rectal bleeding subscore of = 1 point
• Proportion of patients with mucosal healing at Week 32, defined by an endoscopy subscore of = 1 point

Safety Endpoints:

• The incidence and type of AEs, SAEs, AEs leading to discontinuation of study treatment, target AEs of special interest, laboratory abnormalities, vital signs, ECG, and physical exam abnormalities

PK and PD Endpoints:

• PK assessments will include PK sampling to determine plasma concentration of RPC1063 and active metabolites at scheduled assessments during the treatment period (see Table 1 [IP and MP] and Table 2 [OLP] Schedule of Events)
• Absolute lymphocyte count (ALC) derived from blinded hematology laboratory results
• Plasma protein biomarkers (cytokines, chemokines, other inflammatory proteins)
• Stool analysis for fecal biomarkers – fecal lactoferrin and calprotectin
• Total immunoglobulins (Igs) - IgA, IgG, IgM

Secondary ID(s)

2012-003123-38-BE

NCT01647516

RPC01-202

Source(s) of Monetary Support

Celgene International II Sàrl (CIS II)

Ethics review

Status: Approved
Approval date: 09/01/2013
Contact: