Safety and Efficacy Study of PTG-100 in the Treatment of Moderate to Severe Ulcerative Colitis

A Phase 2b Randomised, Double-blind, Placebo-controlled, Parallel, Adaptive 2-Stage, Multi-Centre Study to Evaluate the Safety and Efficacy of Oral PTG-100 Induction in Subjects With Moderate to Severe Active Ulcerative Colitis

The main objectives of this study are to evaluate the efficacy, safety, and tolerability of daily doses of PTG-100 in subjects with moderate to severe ulcerative colitis (UC).

This is a Phase II multi-centre, double blind, randomised, placebo-controlled, clinical study to evaluate the efficacy, safety, and tolerability of an oral peptide, PTG-100, administered as capsules for 12 weeks in subjects with moderate to severe UC.

Following screening procedures and confirmation of subject eligibility, subjects will be randomised 1:1:1:1 to one of three daily doses of PTG-100 (150, 300 or 900 mg) or placebo. Stratification will be based on subjects' prior treatment with anti-TNF agents, with a maximum of 50% of subjects with prior unsuccessful anti-TNF agent treatments. Subjects will be treated with study drug for 12 weeks. Sigmoidoscopies will be performed at the Screening Visit and on Week 12. A final Follow Up Visit will occur on Week 16, when subject has been off study treatment for 4 weeks. Clinical, safety, pharmacokinetic (PK) and pharmacodynamic (PD) parameters will be evaluated on an ongoing basis during the 16 week study.

Inclusion Criteria include:

• Male and female subjects age 18 to 80 years, inclusive
• Diagnosis of UC for at least 2 months prior to screening
• Moderate to severe active UC as defined by Mayo Score of 6 to 12 inclusive (range of 0-12) at baseline with endoscopy score of at least 2 (range 0-3)
• Subject must have had an inadequate response, loss of response to or intolerance to at least of of the following medications: immunomodulators, TNF-alpha antagonists or corticosteroids
• Subject is unlikely to conceive, as defined by one of the following: a) subject is male, b) subject is surgically sterilized female, c) subject is post-menopausal female >= 45 years of age with clinical documentation of menopause, or d) subject is woman of child bearing potential (WOCBP) and agrees to abstain from heterosexual activity, use adequate hormonal contraception or use double barrier contraception.
• For WOCBP, a negative pregnancy test at screening and within 24 hours of first dose of study medication

Exclusion Criteria include:

• Subject has Crohn's Disease (CD), indeterminate colitis (IC) or presence or history of fistula with CD
• History of toxic megacolon, abdominal abscess, symptomatic colonic stricture or stoma; history or is at imminent risk of colectomy
• History or current evidence of colonic dysplasia or adenomatous colonic polyps
• Current bacterial or parasitic pathogenic enteric infection, including Clostridium difficile, infection with hepatitis B or C virus, infection with human immunodeficiency virus, infection requiring hospitalisation or intravenous antimicrobial therapy, or opportunistic infection within 6 months, any infection requiring antimicrobial therapy within 2 weeks, history of more than one episode of herpes zoster or any episode of disseminated zoster
• Live virus vaccination within one month prior to screening
• Subject has a concurrent clinically significant, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, might confound the study results or poses additional risk to the subject
• Known primary or secondary immunodeficiency
• History of myocardial infarction, unstable angina, transient ischaemic attack, decompensated heart failure requiring hospitalisation, congestive heart failure (NYHA Class 3 or 4), uncontrolled arrhythmias, cardiac revascularisation, stroke, uncontrolled hypertension, or uncontrolled diabetes within 6 months of screening
• Clinically meaningful laboratory abnormalities at screening
• Pregnant or lactating females
• Any surgical procedure requiring general anaesthesia within one month prior to screening, or planned elective surgery during the study
• History of malignant neoplasms or carcinoma in situ within 5 years prior to screening
• History of any major neurological disorders, as judged by the Investigator, or positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist
• Current or recent history of alcohol dependence or illicit drug use within 1 year prior to screening.
• Subject is mentally or legally incapacitated at the time of screening visit or has a history of clinically significant psychiatric disorders that would impact the subject's ability to participate in the trial according to the investigator
• Unable to attend study visits or comply with procedures
• Concurrent participation in any other interventional study.