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

NCT ID: NCT03850509

Last Updated: 2021-06-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-25
• Study Completion Date: 2020-05-22

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.

Detailed Description

OPS-2071 is a novel agent that is currently being developed for the treatment of Crohn's disease and was previously investigated for the treatment of enteric infection, including those caused by Clostridium difficile. OPS-2071 belongs to the fluoroquinolone family of compounds and has shown anti-inflammatory and potent antibacterial activity in in vitro and in vivo assays. OPS-2071 is anticipated to be effective in the treatment of Crohn's disease due to its unique mode of action. In vitro investigations of OPS-2071 showed a dual mechanism of action, including a potent, broad spectrum antibacterial effect and a strong anti-inflammatory effect that translated into significant attenuation of numerous cytokines, including TNF-alpha (TNF-α) screening.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

OPS-2071 150 mg BID

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.

Group Type: EXPERIMENTAL

OPS-2071

Intervention Type: DRUG

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

OPS-2071 300 mg BID

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.

Group Type: EXPERIMENTAL

OPS-2071

Intervention Type: DRUG

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

OPS-2071 600 mg BID

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.

Group Type: EXPERIMENTAL

OPS-2071

Intervention Type: DRUG

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

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

OPS-2071

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Conditions or circumstances that could prevent completion of the trial according to the judgment of the investigator, including an uncontrolled comorbidity, heart condition, or dysfunction of any other organ; peripheral neuropathy; known arrhythmias, atrial fibrillation, or paroxysmal tachycardia; history of myasthenia gravis; history of drug or alcohol abuse, mental illness, or noncompliance with treatments or visits; or known immune-deficiency.
• HIV infection, viral hepatitis, prior organ transplant, or malignant disease that is not in remission for at least 3 years, with the exception of basal cell carcinoma.
• Participants who have used any investigational drug within 2 months prior to screening.
• Blood donation in the last 2 months.
• Use of inhibitors of UGT1A1 and UGT1A9 (eg, Silybin, diclofenac, mycophenolic acid, efavirenz, regorafenib) and BCRP (eg, Estrone, 17β-estradiol, flavonoids, herb extracts, gefitinib, imatinib, tamoxifen, novobiocin, nelfinavir, ritonavir, dipyridamole, fumitremorgin C, Ko143, cyclosporine, curcumin, eltrombopag, omeprazole, ivermectin).
• Participants with a history of treatment failure with 2 or more biologics.
• Participants 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.
• Participants with systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg.
• Participants taking quinidine, procainamide, disopyramide, encainide, flecainide, sotalol, amiodarone, ibutilide, dronedarone, or propafenone.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IQVIA Pvt. Ltd

INDUSTRY

Sponsor Role: collaborator

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

United States, California

Los Angeles, California, United States

United States, California

San Carlos, California, United States

United States, Colorado

Colorado Springs, Colorado, United States

United States, Florida

Clearwater, Florida, United States

United States, Florida

Hialeah, Florida, United States

United States, Florida

Kissimmee, Florida, United States

United States, Florida

Naples, Florida, United States

United States, Florida

Orlando, Florida, United States

United States, Florida

Plantation, Florida, United States

United States, Georgia

Decatur, Georgia, United States

United States, Georgia

Doraville, Georgia, United States

United States, Kansas

Shawnee Mission, Kansas, United States

United States, Maryland

Chevy Chase, Maryland, United States

United States, North Carolina

Greenville, North Carolina, United States

United States, Ohio

Cincinnati, Ohio, United States

United States, Ohio

Dayton, Ohio, United States

United States, Oklahoma

Oklahoma City, Oklahoma, United States

United States, South Carolina

Rock Hill, South Carolina, United States

United States, Texas

Austin, Texas, United States

United States, Texas

Harlingen, Texas, United States

United States, Texas

San Antonio, Texas, United States

United States, Texas

Sugar Land, Texas, United States

United States, Texas

Tyler, Texas, United States

United States, Virginia

Lynchburg, Virginia, United States

Poland

Knurów, , Poland

Poland

Lodz, , Poland

Poland

Lodz, , Poland

Poland

Oświęcim, , Poland

Poland

Poznan, , Poland

Poland

Poznan, , Poland

Poland

Rzeszów, , Poland

Countries

United States; Poland

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-000176-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

341-201-00004

Identifier Type: -

Identifier Source: org_study_id