Efficacy and Safety of Oral OPS-2071 in Participants With Crohn's Disease Showing Symptoms of Active Inflammation

NCT03850509 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 341-201-000042019-000176-41
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 31

Brief Summary

The purpose of this study is to evaluate the effects and safety of OPS-2071 (150, 300, or 600 mg twice a day \[BID\]) versus placebo, as add-on therapy in participants with Crohn's disease who show symptoms of active inflammation despite being on ongoing treatment.

Conditions

Crohn's Disease

Keywords

Crohn's disease; Inflammatory bowel disease; Fluoroquinolones; Inflammation; Intestine; Digestive tract; Abdominal pain; Diarrhea

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score

  Clinical remission was defined as CDAI score \<150 at Week 12. The CDAI evaluated severity of signs and symptoms of Chron's Disease. Some components of the CDAI were reported by the investigator (physical examination for the presence of an abdominal mass and extraintestinal complications, laboratory results for hematocrit levels, and weight) while other components were determined with data collected in a participant diary (number of liquid or soft stools, number of antidiarrheal medications, abdominal pain score, and general well-being). The index values of 150 and below were associated with quiescent disease; values above that indicated active disease, values \>=220 indicated moderate to severe disease, and values above 450 were seen with extremely severe disease.

  Week 12

Secondary Outcomes (7)

• Percentage of Participants With Endoscopic Response Based on Simple Endoscopic Score for Crohn's Disease (SES-CD)

  Week 12

• Change From Baseline in the SES-CD Score at Week 12

  Baseline (Day 1) and Week 12

• Percentage of Participants With Two-item Participant Reported Outcome (PRO-2) Remission

  Week 12

• Percentage of Participants With Clinical Response Based on CDAI Score

  Week 12

• Percentage of Participants With Endoscopic Remission Based on SES-CD

  Week 12

Study Arms (4)

OPS-2071 150 mg BID

EXPERIMENTAL

Participants were to receive OPS-2071 150 mg, tablets, orally, twice daily (BID) in the morning and evening (8 to 12 hours apart) with 240 milliliters (mL) of water for up to 12 weeks.

Drug: OPS-2071

OPS-2071 300 mg BID

EXPERIMENTAL

Participants received OPS-2071 300 mg, tablets, orally, BID in the morning and evening (8 to 12 hours apart) with 240 mL of water for up to 6 weeks.

Drug: OPS-2071

OPS-2071 600 mg BID

EXPERIMENTAL

Participants were to receive OPS-2071 600 mg, tablets, orally, BID in the morning and evening (8 to 12 hours apart) with 240 mL of water for up to 12 weeks.

Drug: OPS-2071

Placebo

PLACEBO COMPARATOR

Participants received OPS-2071-matched placebo, tablets, orally, BID in morning and evening (8 to 12 hours apart) with 240 mL of water for up to 4 weeks.

Drug: Placebo

Interventions

OPS-2071 DRUG

OPS-2071 300 mg, tablets, orally, BID.

OPS-2071 150 mg BID; OPS-2071 300 mg BID; OPS-2071 600 mg BID

Placebo DRUG

OPS-2071-matched placebo, tablets, orally, BID.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants between the ages of 18 and 70 years, inclusive
• 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).
• Participants 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 \[TNF-α\] monoclonal antibody), immunosuppressants, low-dose steroids, or 5-aminosalicylic acid (5-ASA) formulations.
• Participants who are on stable Crohn's disease medications for at least 4 weeks.
• Participants with a CDAI score between 180 and 450 points, inclusive.
• Participants who are willing and able to follow the trial protocol and have signed informed consent.

You may not qualify if:

• Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP.
• Sexually active males or WOCBP who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of IMP. If employing birth control, 2 of the following precautions must be used: vasectomy, tubal ligation, intrauterine device, birth control pill, birth control implant, or birth control depot injection. A vaginal diaphragm, condom with spermicide, or sponge with spermicide may also be used as measures to prevent pregnancy, but must be used in combination with at least one of the previous methods.
• Participants taking any nonsteroidal anti-inflammatory drugs that cannot be stopped or replaced.
• 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.
• Participants taking antithrombotic drugs.
• Participants with symptomatic bowel stenosis, fistula, or stoma; or with more than 2 bowel resections.
• Participants with short bowel syndrome.
• participants with known existing aortic aneurysm, or who are at risk for an aortic aneurysm, such as participants with peripheral atherosclerotic vascular diseases, uncontrolled hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and elderly participants (over the age of 70).
• Participants with known or suspected (family history, unexplained syncope) long QT syndrome or QTcF \> 470 msec for females or \> 450 msec for males at baseline.
• Participants with inadequate organ function, as follows:
• Serum creatinine \> 1.5x the upper limit of normal (ULN)
• Aspartate aminotransferase or alanine aminotransferase levels \> 1.5x ULN
• Total bilirubin \> 1.5x ULN. Elevated unconjugated bilirubin related to Gilbert's syndrome is allowed.
• Use of antibiotics (eg. metronidazole, rifaximin, tinidazole, ciprofloxacin, clarithromycin) within 15 days prior to screening or for greater than 2 months within the past year. A short course (maximum of 5 days) of antibiotics will be permitted during the trial, as needed, for indications other than Crohn's disease.
• Known hypersensitivity to quinolones or other significant adverse reaction to quinolones.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• IQVIA Pvt. Ltd: collaborator

Study Sites (31)

United States, California

Los Angeles, California, 90067, United States

Location

United States, California

San Carlos, California, 94070, United States

Location

United States, Colorado

Colorado Springs, Colorado, 80907, United States

Location

United States, Florida

Clearwater, Florida, 33756, United States

Location

United States, Florida

Hialeah, Florida, 33012, United States

Location

United States, Florida

Kissimmee, Florida, 34759, United States

Location

United States, Florida

Naples, Florida, 34102, United States

Location

United States, Florida

Orlando, Florida, 32825, United States

Location

United States, Florida

Plantation, Florida, 33322, United States

Location

United States, Georgia

Decatur, Georgia, 30033, United States

Location

United States, Georgia

Doraville, Georgia, 30362, United States

Location

United States, Kansas

Shawnee Mission, Kansas, 66226, United States

Location

United States, Maryland

Chevy Chase, Maryland, 20815, United States

Location

United States, North Carolina

Greenville, North Carolina, 27834, United States

Location

United States, Ohio

Cincinnati, Ohio, 45219, United States

Location

United States, Ohio

Dayton, Ohio, 45417, United States

Location

United States, Oklahoma

Oklahoma City, Oklahoma, 73112, United States

Location

United States, South Carolina

Rock Hill, South Carolina, 29732, United States

Location

United States, Texas

Austin, Texas, 78704, United States

Location

United States, Texas

Harlingen, Texas, 78550, United States

Location

United States, Texas

San Antonio, Texas, 78229, United States

Location

United States, Texas

Sugar Land, Texas, 77479, United States

Location

United States, Texas

Tyler, Texas, 75701, United States

Location

United States, Virginia

Lynchburg, Virginia, 24502, United States

Location

Poland

Knurów, 44-190, Poland

Location

Poland

Lodz, 90-349, Poland

Location

Poland

Lodz, 90-572, Poland

Location

Poland

Oświęcim, 32-600, Poland

Location

Poland

Poznan, 60-369, Poland

Location

Poland

Poznan, 60-529, Poland

Location

Poland

Rzeszów, 35-326, Poland

Location

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases; Inflammation; Abdominal Pain; Diarrhea

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Signs and Symptoms, Digestive

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Two or more parties are unaware of the intervention assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are assigned to one of two or more groups in parallel for the duration of the study

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: February 21, 2019
• Study Start: February 25, 2020
• Primary Completion: May 22, 2020
• Study Completion: May 22, 2020
• Last Updated: June 15, 2021
• Results First Posted: June 15, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com

Locations

PL (7); US (24)