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

Phase 2

Completed

• Conditions: chronic inflammatory bowel disease; ulcerative colitis; 10018027

• Registration Number: NL-OMON45322
• Lead Sponsor: Protagonist Therapeutics Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 6

Inclusion Criteria

The following are the inclusion criteria. Subjects must meet ALL of the following inclusion criteria to be enrolled. Subjects may be screened up to 3 different times separated by at least 14 days.
1. Male and female subjects aged 18 to 80 years, inclusive.
2. Diagnosis of UC for >= 2 months prior to screening, with a history of disease activity extending beyond the rectum; if the UC has been present for > 10 years, a colonoscopy with biopsy must have been performed within 2 years of screening to rule out dysplasia. Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age > 50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance per local standards and guidelines (may be performed during screening). Subjects with extensive colitis or pancolitis of > 8 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial Screening visit (may be performed during screening).
3. Moderate to severe active UC as defined by complete Mayo Score of 6 to 12, inclusive (range 0 to 12), at baseline (pre-randomisation) with endoscopy score of at least 2 (range 0 to 3), extending 15 cm or more from the anal verge, as determined by blinded central read, within 14 days of randomisation.
4. Demonstrated, over the previous 5-year period, an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents as defined below:
a. Immunomodulators
i. Signs and symptoms of persistently active disease despite a history of at least one >= 8-week regimen of oral azathioprine (>= 1.5 mg/kg) or 6-mercaptopurine (6-MP) (>= 0.75 mg/kg), OR
ii. History of intolerance of at least 1 immunomodulator (including, but not limited to, nausea/vomiting, abdominal pain, pancreatitis, liver function test abnormalities, lymphopaenia, thiopurine S-methyltransferase genetic mutation, and/or infection)
b. TNF-a antagonists
i. Signs and symptoms of persistently active disease despite a history of at least 1 induction regimen of at least 6 weeks duration, OR
ii. Recurrence of symptoms during maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify), OR
iii. History of intolerance (including, but not limited to, infusion- or injection-related reaction, demyelination, congestive heart failure, and infection)
Note: A maximum of 50% of randomised subjects may have had prior treatment with TNF-a antagonists.For subjects in the Netherlands, only subjects who have had prior exposure to anti-TNF agents will be allowed to enrol in the study (as confirmed by medical record documentation or by self-reporting).
c. Corticosteroids
i. Signs and symptoms of persistently active disease despite a history of at least one 4-week induction regimen that included a dose equivalent to prednisone 30 mg daily orally for 2 weeks or intravenous (IV) for 1 week, OR
ii. Two failed attempts to taper corticosteroids to below a dose equivalent to prednisone 10 mg daily orally on 2 separate occasions, OR
iii. History of intolerance of corticosteroids (including, but not limited to, Cushing*s syndrome, osteopaenia/ osteoporosis, hyperglycaemia, insomnia, and infection).
5. Subject is unlikely to conceive, as indicated by at least one *yes* answer to the following criteria:
a. Subject is a male
b. Subject is a surgicall

Exclusion Criteria

The following are the exclusion criteria; subjects must meet NONE of the following exclusion criteria to be enrolled.
Gastrointestinal exclusion criteria
1. Subject with Crohn*s disease (CD), indeterminate colitis, or presence or history of fistula consistent with CD.
2. History of toxic megacolon, abdominal abscess, symptomatic colonic stricture, or stoma; history of extensive colonic resection, or subtotal or total colectomy; or is at imminent risk of colectomy.
3. History or current evidence of colonic dysplasia or adenomatous colonic polyps. Note: Subjects will not be excluded from the study because of a pathology finding of indefinite dysplasia with reactive atypia. Subjects with resected adenomatous polyps may be enrolled.
Infectious disease exclusion criteria
4. Current bacterial or parasitic pathogenic enteric infection, including Clostridium difficile,(confirmed by toxin result), current infection with hepatitis B or C virus (subjects treated for HCV infection must have evidence of sustained virologic response 12 weeks after the end of treatment [SVR12],, infection requiring hospitalisation or IV antimicrobial therapy, opportunistic infection within 6 months of dosing, any infection requiring antimicrobial therapy within 2 weeks of dosing, history of more than one episode of herpes zoster, history of infection with human immunodeficiency virus, or any episode of disseminated zoster. Note: Subjects with a history of C. difficile infection treated with antibiotics with or without faecal microbial transplant may be rescreened after 2 weeks following completion of treatment.
5. Live virus vaccination within 1 month prior to screening.
General exclusion criteria
6. Subject has a concurrent clinically significant, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, haematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject by their participation in the study.
Note: Subjects with a history of uncomplicated kidney stones, childhood asthma, or concurrent stable and well-controlled asthma may be enrolled in the study at the discretion of the Investigator.
7. Known primary or secondary immunodeficiency.
8. History of myocardial infarction, unstable angina, transient ischaemic attack, decompensated heart failure requiring hospitalisation, congestive heart failure (New York Heart Association Class 3 or 4), uncontrolled arrhythmias, cardiac revascularisation, stroke, uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg or diastolic BP > 100 mmHg at Screening), or uncontrolled diabetes (haemoglobin A1c > 9% or > 1 episode of severe hypoglycaemia) within 6 months of screening.
9. Clinically meaningful laboratory abnormalities at Screening including, but not limited to, the ranges below:
a. Absolute neutrophil count < 1000/µL
b. Platelet count < 100,000/µL
c. Haemoglobin < 9 g/dL
d. Creatinine >= 1.5 mg/dL
e. alanine aminotransferase or aspartate aminotransferase >= 2.5 x upper limit of normal (ULN) or bilirubin > 1.5 x ULN
10. Pregnant or lactating females.
11. Any surgical procedure requiring general anaesthesia within 1 month prior to screening, or planned elective surgery during the study.
12. History of malignant neoplasms or carcinoma in si

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary efficacy endpoint is the:<br /><br>1. Proportion of subjects receiving PTG-100 with clinical remission at Week 12<br /><br>compared with placebo<br /><br><br /><br>Clinical remission is defined as follows, using the Mayo subscores of stool<br /><br>frequency, rectal bleeding, and endoscopy:<br /><br>• Stool frequency subscore of 0 or 1 with a pre-specified change of 1 or more<br /><br>from baseline<br /><br>• Rectal bleeding subscore of 0<br /><br>• Endoscopy subscore of 0 or 1 (modified so that a score of 1 does not include<br /><br>friability)<br /><br><br /><br><br /><br><br /><br>The primary safety endpoint is:<br /><br>1. Proportion of subjects with at least 1 AE comparing individual PTG-100<br /><br>dosing groups with placebo</p><br>