A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Trial to Assess the Efficacy and Safety of Orally Administered OPS-2071 for 12 Weeks in Subjects With Crohn’s Disease Showing Symptoms of Active Inflammation Despite Ongoing Treatment

• Register: EUCTR
• Last refreshed on: 21 September 2020
• Main ID: EUCTR2019-000176-41-DE
• Date of registration: 15/08/2019
• Prospective Registration: Yes
• Primary sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Public title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Trial to Assess the Efficacy and Safety of Orally Administered OPS-2071 for 12 Weeks in Subjects With Crohn’s Disease Showing Symptoms of Active Inflammation Despite Ongoing Treatment
• Scientific title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Trial to Assess the Efficacy and Safety of Orally Administered OPS-2071 for 12 Weeks in Subjects With Crohn’s Disease Showing Symptoms of Active Inflammation Despite Ongoing Treatment
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-000176-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Germany, Hungary, Italy, Poland, Russian Federation, Ukraine, United States

Contacts

• Name: Kimberly Sikes
• Affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.

• Name: Kimberly Sikes
• Affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1) Diagnosis of Crohn's disease localized in the ileum and/or colon, with active mucosal inflammation and visible
lesion(s), documented by centrally read ileocolonoscopy and a Simple Endoscopic Score for Crohn’s Disease
(SES-CD) = 6 (= 4 for isolated ileal disease).
2) Subjects who do not have an optimal response (daily stool frequency > 3 and pain score > 1) to their current ongoing
treatment of biologics (eg, first anti-tumor necrosis factor-alpha [TNF-a] monoclonal antibody), immunosuppressants, low-dose steroids, or 5-aminosalicylic acid (5-ASA) formulations.
3) Subjects who are on stable Crohn’s disease medications for at least 4 weeks.
4) Subjects with a CDAI score between 180 and 450 points, inclusive.
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 210
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
1) Low-dose steroids may be tapered down during the trial, based on inflammatory biomarkers and the investigator’s judgment.
2) Use of prednisone or prednisolone > 30 mg/day or budesonide > 9 mg/day within 4 weeks prior to screening; or intravenous steroids within 4 weeks prior to screening.
3) Subjects with known or suspected (family history, unexplained syncope) long QT syndrome or QT interval corrected for heart rate by the Fridericia formula (QTcF) > 470 msec for females or > 450 msec for males at baseline.
4) Subjects with known existing aortic aneurysm, or who are at risk for an aortic aneurysm, such as subjects with
peripheral atherosclerotic vascular diseases, uncontrolled hypertension, certain genetic conditions such as Marfan
syndrome and Ehlers-Danlos syndrome, and elderly subjects (over the age of 70).
5) Subjects with inadequate organ function, as follows: Serum creatinine > 1.5 x the upper limit of normal (ULN); Aspartate aminotransferase or alanine aminotransferase levels > 1.5 x ULN; Total bilirubin > 1.5 x ULN. Elevated unconjugated bilirubin related to Gilbert's syndrome is allowed.
6) Known hypersensitivity to quinolones.
7) Subjects with a history of treatment failure with 2 or more biologics.
8) Subjects with risk factors for tendon rupture (ie, psoriasis, ankylosing spondylitis, competitive athletes, renal failure,
diabetes mellitus) or who have a history of tendon rupture and/or ongoing tendinopathy.
9) Subjects with systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg.
10) Subjects taking quinidine, procainamide, disopyramide, encainide, flecainide, sotalol, amiodarone, ibutilide, dronedarone, or propafenone.


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

Health Condition(s) or Problem(s) studied

Crohn's Disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

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

Intervention(s)

Product Name: OPS-2071
Product Code: OPS-2071
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OPS-2071
CAS Number: 1426216-93-4
Current Sponsor code: OPS-2071
Other descriptive name: OPS-2071
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: OPS-2071
Product Code: OPS-2071
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OPS-2071
CAS Number: 1426216-93-4
Current Sponsor code: OPS-2071
Other descriptive name: OPS-2071
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The percentage of subjects who, at Week 12, achieve clinical remission (defined as a CDAI score < 150).

Secondary Objective: To determine the safety and tolerability of OPS-2071 (150, 300, or 600 mg BID) add-on therapy administered orally for 12 weeks in subjects with Crohn’s disease showing symptoms of active inflammation despite ongoing treatment.

Main Objective: To investigate the therapeutic effect of OPS-2071 (150, 300, or 600 mg twice a day [BID]) add-on therapy administered orally for 12 weeks in subjects with Crohn’s disease showing symptoms of active inflammation despite ongoing treatment.

Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12

Secondary end point(s): Efficacy endpoints:
1) The percentage of subjects with endoscopic response, defined as a reduction of the SES-CD by at least 50%, at Week 12.
2) Change from baseline in the SES-CD score.
3) The percentage of subjects with PRO-2 remission (defined as stool frequency = 3 times per day and abdominal pain = 1) at Week 12.
4) The percentage of subjects with clinical response, defined as at least a 25% decrease in the CDAI score, at Week 12.
5) The percentage of subjects who, at Week 12, achieve endoscopic remission (defined as a SES-CD score of 0 to 2; or a score of 0 to 4, with no individual subscore greater than 1).
6) The percentage of subjects with a decrease from baseline of = 100 points in the CDAI score.

Safety endpoints:
The percentage of subjects by specific AEs, which will be recorded with the onset date, resolution or stabilization date, severity grade, and relatedness to IMP.

Secondary ID(s)

341-201-00004

NCT03850509

Source(s) of Monetary Support

Otsuka Pharmaceutical Development & Commercialization, Inc.

Ethics review

Status: Approved
Approval date:
Contact: