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

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ClinicalTrials.gov Identifier: NCT02895100
Recruitment Status : Terminated (Data Monitoring Committee discontinued the trial due to futility-based outcome)
First Posted : September 9, 2016
Results First Posted : March 22, 2021
Last Update Posted : October 22, 2021
Sponsor:
Information provided by (Responsible Party):
Protagonist Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE September 4, 2016
First Posted Date  ICMJE September 9, 2016
Results First Submitted Date  ICMJE February 22, 2021
Results First Posted Date  ICMJE March 22, 2021
Last Update Posted Date October 22, 2021
Study Start Date  ICMJE December 2016
Actual Primary Completion Date March 26, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2021)
Proportion of Subjects Receiving PTG-100 With Clinical Remission at Week 12 Compared With Placebo [ Time Frame: 12 week treatment period ]
The primary efficacy endpoint for this study was the proportion of subjects receiving PTG-100 with clinical remission at Week 12. Clinical remission was defined using the Mayo subscores of stool frequency, rectal bleeding, and endoscopy.
Original Primary Outcome Measures  ICMJE
 (submitted: September 4, 2016)
  • Proportion of subjects receiving PTG-100 with clinical remission at Week 12 compared with placebo [ Time Frame: 12 week treatment period ]
  • Proportion of subjects with at least 1 adverse event (AE) comparing individual PTG-100 dosing groups with placebo [ Time Frame: Up to approximately 16 weeks ]
    An adverse event is any undesirable experience associated with the use of a medical product in a patient.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2016)
  • Proportion of subjects with endoscopic response at Week 12 (defined as an endoscopic subscore of 0 or 1) [ Time Frame: 12 week treatment period ]
    Mayo endoscopic subscore is one of the Mayo score components and its value ranges from 0 to 3 points
  • Proportion of subjects with clinical response at Week 12 (defined as at least 1 point and 30% reduction from baseline in rectal bleeding and stool frequency subscores) [ Time Frame: 12 week treatment period ]
    Mayo stool frequency and rectal bleeding subscores are two of the Mayo score components and each subscore value ranges from 0 to 3 points
  • Mean change in endoscopy subscore from baseline to Week 12 [ Time Frame: 12 week treatment period ]
    Mayo endoscopic subscore is one of the Mayo score components and its value ranges from 0 to 3 points
  • Mean change in rectal bleeding and stool frequency subscores from baseline to Weeks 2, 4, 6, 8, 10, 12, and 16 [ Time Frame: 12 week treatment period ]
    Mayo stool frequency and rectal bleeding subscores are two of the Mayo score components and each subscore value ranges from 0 to 3 points
  • Proportion of subjects with endoscopic remission at Week 12 (defined as an endoscopic subscore of 0) [ Time Frame: 12 week treatment period ]
    Mayo endoscopic subscore is one of the Mayo score components and its value ranges from 0 to 3 points
  • Mean change in Mayo Score from baseline to Week 12 [ Time Frame: 12 week treatment period ]
    The Complete Mayo Score is the sum of 4 subscores (stool frequency, rectal bleeding, endoscopic findings, physician's global assessment. Each subscore ranges from 0 to 3, with the higher value indicating more severe disease. The total Complete Mayo Score ranges from 0 to 12.
  • Mean change in Partial Mayo Score from baseline to Weeks 2, 4, 6, 8, 12, and 16 [ Time Frame: 12 week treatment period ]
    The Partial Mayo Score is the sum of 3 subscores (stool frequency, rectal bleeding, physician's global assessment. Each subscore ranges from 0 to 3, with the higher value indicating more severe disease. The Partial Mayo Score ranges from 0 to 9.
  • Mean change in fecal calprotectin levels from baseline to Weeks 6 and 12 [ Time Frame: 12 week treatment period ]
    Fecal calprotectin is used to detect inflammation in the intestines. For patients with ulcerative colitis (UC), it is a measure of the activity and severity of UC.
  • Mean change in Inflammatory Bowel Disease Questionnaire (IBDQ) score from baseline to Week 12 [ Time Frame: 12 week treatment period ]
    IBDQ is a widely used questionnaire for health-related quality of life assessment in patients with inflammatory bowel diseases (IBDs)
  • Proportion of subjects developing antidrug antibodies (ADA) [ Time Frame: 16 week study duration ]
    ADA are antibodies which may develop as a result of an immunological reaction to a pharmaceutical agent. ADAs may inactivate the therapeutic effects of a drug and, in rare cases, cause adverse effects.
  • Frequency and type of adverse events (AE) (affecting ≥ 5% of subjects) [ Time Frame: 16 week study duration ]
    An adverse event is any undesirable experience associated with the use of a medical product in a patient.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of PTG-100 in the Treatment of Moderate to Severe Ulcerative Colitis
Official Title  ICMJE 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
Brief Summary 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).
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE
  • Drug: PTG-100
    Daily dosing of PTG-100 by subject for a 12 week treatment period.
  • Drug: Placebo
    Daily dosing of Placebo capsules by subject for a 12 week treatment period.
Study Arms  ICMJE
  • Experimental: PTG-100 (150 mg QD)
    Low dose
    Intervention: Drug: PTG-100
  • Experimental: PTG-100 (300 mg QD)
    Medium dose
    Intervention: Drug: PTG-100
  • Experimental: PTG-100 (900 mg QD)
    High dose
    Intervention: Drug: PTG-100
  • Placebo Comparator: Placebo group
    Placebo control
    Intervention: Drug: Placebo
Publications * Sandborn W, Mattheakis LC, Modi NB, Pugatch D, Bressler B, Lee S, Bhandari R, Kanwar B, Shames R, D'Haens G, Schreiber S, Danese S, Feagan B, Pai RK, Liu DY, Gupta S. PTG-100, an Oral α4β7 Antagonist Peptide: Preclinical Development and Phase 1 and 2a Studies in Ulcerative Colitis. Gastroenterology. 2021 Aug 30. pii: S0016-5085(21)03463-6. doi: 10.1053/j.gastro.2021.08.045. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 24, 2021)
98
Original Estimated Enrollment  ICMJE
 (submitted: September 4, 2016)
240
Actual Study Completion Date  ICMJE March 26, 2018
Actual Primary Completion Date March 26, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Bosnia and Herzegovina,   Canada,   Croatia,   Czechia,   Germany,   Hungary,   Korea, Republic of,   Latvia,   Netherlands,   New Zealand,   Poland,   Russian Federation,   Serbia,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02895100
Other Study ID Numbers  ICMJE PTG-100-02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Protagonist Therapeutics, Inc.
Study Sponsor  ICMJE Protagonist Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Director Clinical Development Protagonist Therapeutics, Inc.
PRS Account Protagonist Therapeutics, Inc.
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP