Efficacy and Safety of Oral OPS-2071 in Participants With Crohn's Disease Showing Symptoms of Active Inflammation
Condition: Crohn's Disease
MeSH terms: Crohn Disease; Inflammation
Intervention: OPS-2071; Placebo
Intervention description: OPS-2071 300 mg, tablets, orally, BID.; OPS-2071-matched placebo, tablets, orally, BID.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants are assigned to one of two or more groups in parallel for the duration of the study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Two or more parties are unaware of the intervention assignment.
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Crohn's disease; Inflammatory bowel disease; Fluoroquinolones; Inflammation; Intestine; Digestive tract; Abdominal pain; Diarrhea

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.
    

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.