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

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.

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.

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.