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

May 19, 2021 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Poland
      • Knurów, Poland, 44-190
        • Poland
      • Oświęcim, Poland, 32-600
        • Poland
      • Poznań, Poland, 60-369
        • Poland
      • Poznań, Poland, 60-529
        • Poland
      • Rzeszów, Poland, 35-326
        • Poland
      • Łódź, Poland, 90-349
        • Poland
      • Łódź, Poland, 90-572
        • Poland
  • United States
    • California
      • Los Angeles, California, United States, 90067
        • United States, California
      • San Carlos, California, United States, 94070
        • United States, California
    • Colorado
      • Colorado Springs, Colorado, United States, 80907
        • United States, Colorado
    • Florida
      • Clearwater, Florida, United States, 33756
        • United States, Florida
      • Hialeah, Florida, United States, 33012
        • United States, Florida
      • Kissimmee, Florida, United States, 34759
        • United States, Florida
      • Naples, Florida, United States, 34102
        • United States, Florida
      • Orlando, Florida, United States, 32825
        • United States, Florida
      • Plantation, Florida, United States, 33322
        • United States, Florida
    • Georgia
      • Decatur, Georgia, United States, 30033
        • United States, Georgia
      • Doraville, Georgia, United States, 30362
        • United States, Georgia
    • Kansas
      • Shawnee Mission, Kansas, United States, 66226
        • United States, Kansas
    • Maryland
      • Chevy Chase, Maryland, United States, 20815
        • United States, Maryland
    • North Carolina
      • Greenville, North Carolina, United States, 27834
        • United States, North Carolina
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • United States, Ohio
      • Dayton, Ohio, United States, 45417
        • United States, Ohio
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • United States, Oklahoma
    • South Carolina
      • Rock Hill, South Carolina, United States, 29732
        • United States, South Carolina
    • Texas
      • Austin, Texas, United States, 78704
        • United States, Texas
      • Harlingen, Texas, United States, 78550
        • United States, Texas
      • San Antonio, Texas, United States, 78229
        • United States, Texas
      • Sugar Land, Texas, United States, 77479
        • United States, Texas
      • Tyler, Texas, United States, 75701
        • United States, Texas
    • Virginia
      • Lynchburg, Virginia, United States, 24502
        • United States, Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: OPS-2071
OPS-2071 300 mg, tablets, orally, BID.
Experimental: 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.
Drug: OPS-2071
OPS-2071 300 mg, tablets, orally, BID.
Experimental: 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.
Drug: OPS-2071
OPS-2071 300 mg, tablets, orally, BID.
Placebo Comparator: 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.
Drug: Placebo
OPS-2071-matched placebo, tablets, orally, BID.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieved Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score
Time Frame: Week 12
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Endoscopic Response Based on Simple Endoscopic Score for Crohn's Disease (SES-CD)
Time Frame: Week 12
Endoscopic response was defined as a reduction of the SES-CD by at least 50%, at Week 12. The SES-CD is a total score that indicates endoscopic disease activity status based on endoscopy results regarding the size of ulcers, surface ulceration, affected surface size, and presence of luminal narrowing. Each item is scored from 0-3, with total score from 0-60 . Higher score indicates more severe endoscopic activity.
Week 12
Change From Baseline in the SES-CD Score at Week 12
Time Frame: Baseline (Day 1) and Week 12
The SES-CD is a total score that indicates endoscopic disease activity status based on endoscopy results regarding the size of ulcers, surface ulceration, affected surface size, and presence of luminal narrowing. Each item is scored from 0-3, with a total score from 0-60. A higher score indicates more severe endoscopic activity. A negative change from baseline indicates improvement.
Baseline (Day 1) and Week 12
Percentage of Participants With Two-item Participant Reported Outcome (PRO-2) Remission
Time Frame: Week 12
PRO-2 remission was defined as stool frequency =< 3 times per day and abdominal pain =< 1 at Week 12. The PRO-2 is a symptom control measure based on 2 participant-reported components (stool frequency and abdominal pain) of the CDAI (on an 11-point scale where 0=no pain to 10=worst imaginable pain). A weekly score was calculated for the liquid or soft stool frequency and a separate weekly score was calculated for abdominal pain, in each case based on daily symptom reporting. PRO2 is a composite index consisting of weighted scoring of both variables. PRO2 scores ranges from 0 to approximately 45, higher score indicates higher disease activity.
Week 12
Percentage of Participants With Clinical Response Based on CDAI Score
Time Frame: Week 12
Clinical response was defined as at least a 25% decrease in the CDAI score at Week 12. The CDAI evaluated the 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
Percentage of Participants With Endoscopic Remission Based on SES-CD
Time Frame: Week 12
Endoscopic remission was defined as an SES-CD total score of 0 to 2; or a score of 0 to 4, with no individual subscore greater than 1 at Week 12. The SES-CD is a total score that indicates endoscopic disease activity status based on endoscopy results regarding the size of ulcers, surface ulceration, affected surface size, and presence of luminal narrowing. Each item is scored from 0-3, with a total score from 0-60. A higher score indicates more severe endoscopic activity.
Week 12
Percentage of Participants With a Decrease in the CDAI Score at Week 12
Time Frame: Week 12
Percentage of participants who had a decrease of at least => 100 points in CDAI scores were to be reported. The CDAI evaluated the 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
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Time Frame: From the signing of the informed consent form up to early termination (up to approximately 9 weeks)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant and that does not necessarily have a causal relationship with the treatment. An SAE is defined as any fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-patient hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the subject and may have required medical or surgical intervention. A TEAE is defined as an AE that occurred after the administration of investigational medicinal product (IMP).
From the signing of the informed consent form up to early termination (up to approximately 9 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
IQVIA Pvt. Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 25, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 22, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 22, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 15, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 20, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 21, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 15, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 341-201-00004
  • 2019-000176-41 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

IPD Sharing 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.

IPD Sharing 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

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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