Clinical trial NCT02895100: Safety and Efficacy Study of PTG-100 in the Treatment of Moderate to Severe Ulcerative Colitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: ulcerative colitis
inflammatory bowel disease
PROPEL
Propel Study
Lead sponsor: Protagonist Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-09-09
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Subjects Receiving PTG-100 With Clinical Remission at Week 12 Compared With Placebo
timeFrame: 12 week treatment period
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator # 101
state: California
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator # 102
state: California
city: Colorado Springs
country: United States
facility: Site Reference ID/Investigator # 125
state: Colorado
city: Miami
country: United States
facility: Site Reference ID/Investigator # 120
state: Florida
city: Port Orange
country: United States
facility: Site Reference ID/Investigator # 106
state: Florida
city: Saint Augustine
country: United States
facility: Site Reference ID/Investigator # 115
state: Florida
city: Sweetwater
country: United States
facility: Site Reference ID/Investigator # 116
state: Florida
city: Atlanta
country: United States
facility: Site Reference ID/Investigator # 100
state: Georgia
city: Marietta
country: United States
facility: Site Reference ID/Investigator # 104
state: Georgia
city: Suwanee
country: United States
facility: Site Reference ID/Investigator # 112
state: Georgia
city: Chicago
country: United States
facility: Site Reference ID/Investigator # 107
state: Illinois
city: Bastrop
country: United States
facility: Site Reference ID/Investigator # 126
state: Louisiana
city: Shreveport
country: United States
facility: Site Reference ID/Investigator # 114
state: Louisiana
city: Chevy Chase
country: United States
facility: Site Reference ID/Investigator # 117
state: Maryland
city: Great Neck
country: United States
facility: Site Reference ID/Investigator # 109
state: New York
city: New York
country: United States
facility: Site Reference ID/Investigator # 122
state: New York
city: Cincinnati
country: United States
facility: Site Reference ID/Investigator # 119
state: Ohio
city: Hermitage
country: United States
facility: Site Reference ID/Investigator # 110
state: Tennessee
city: Nashville
country: United States
facility: Site Reference ID/Investigator # 128
state: Tennessee
city: DeSoto
country: United States
facility: Site Reference ID/Investigator # 118
state: Texas
city: Richmond
country: United States
facility: Site Reference ID/Investigator # 113
state: Virginia
city: Murdoch
country: Australia
facility: Site Reference ID/Investigator # 901
state: Western Australia
city: Herston
country: Australia
facility: Site Reference ID/Investigator # 908
city: South Brisbane
country: Australia
facility: Site Reference ID/Investigator # 900
city: Subiaco
country: Australia
facility: Site Reference ID/Investigator # 907
city: Gent
country: Belgium
facility: Site Reference ID/Investigator # 559
city: Kortrijk
country: Belgium
facility: Site Reference ID/Investigator # 533
city: Leuven
country: Belgium
facility: Site Reference ID/Investigator # 505
city: Mostar
country: Bosnia and Herzegovina
facility: Site Reference ID/Investigator # 573
city: Tuzla
country: Bosnia and Herzegovina
facility: Site Reference ID/Investigator # 571
city: Vancouver
country: Canada
facility: Site Reference ID/Investigator # 103
state: British Columbia
city: London
country: Canada
facility: Site Reference ID/Investigator # 105
state: Ontario
city: Osijek
country: Croatia
facility: Site Reference ID/Investigator #556
city: Split
country: Croatia
facility: Site Reference ID/Investigator # 550
city: Zagreb
country: Croatia
facility: Site Reference ID/Investigator # 562
city: Nový Hradec Králové
country: Czechia
facility: Site Reference ID/Investigator # 517
city: Zlín
country: Czechia
facility: Site Reference ID/Investigator # 539
city: Berlin
country: Germany
facility: Site Reference ID/Investigator # 560
city: Berlin
country: Germany
facility: Site Reference ID/Investigator # 542
city: Kiel
country: Germany
facility: Site Reference ID/Investigator # 532
city: Leipzig
country: Germany
facility: Site Reference ID/Investigator # 506
city: Mannheim
country: Germany
facility: Site Reference ID/Investigator # 572
city: Münster
country: Germany
facility: Site Reference ID/Investigator # 538
city: Tuebingen
country: Germany
facility: Site Reference ID/Investigator # 574
city: Ulm
country: Germany
facility: Site Reference ID/Investigator # 541
city: Budapest
country: Hungary
facility: Site Reference ID/Investigator # 554
city: Budapest
country: Hungary
facility: Site Reference ID/Investigator # 558
city: Debrecen
country: Hungary
facility: Site Reference ID/Investigator # 552
city: Eger
country: Hungary
facility: Site Reference ID/Investigator # 567
city: Kistarcsa
country: Hungary
facility: Site Reference ID/Investigator # 557
city: Mosonmagyaróvár
country: Hungary
facility: Site Reference ID/Investigator # 544
city: Sopron
country: Hungary
facility: Site Reference ID/Investigator # 563
city: Daegu
country: Korea, Republic of
facility: Site Reference ID/Investigator # 906
city: Seoul
country: Korea, Republic of
facility: Site Reference ID/Investigator # 905
city: Seoul
country: Korea, Republic of
facility: Site Reference ID/Investigator # 904
city: Riga
country: Latvia
facility: Site Reference ID/Investigator # 501
city: Riga
country: Latvia
facility: Site Reference ID/Investigator # 545
city: Amsterdam
country: Netherlands
facility: Site Reference ID/Investigator # 568
city: Dunedin
country: New Zealand
facility: Site Reference ID/Investigator # 903
city: Newton
country: New Zealand
facility: Site Reference ID/Investigator # 902
city: Kielce
country: Poland
facility: Site Reference ID/Investigator # 529
city: Krakow
country: Poland
facility: Site Reference ID/Investigator # 540
city: Kraków
country: Poland
facility: Site Reference ID/Investigator # 576
city: Ksawerów
country: Poland
facility: Site Reference ID/Investigator # 512
city: Lodz
country: Poland
facility: Site Reference ID/Investigator # 530
city: Lodz
country: Poland
facility: Site Reference ID/Investigator # 518
city: Poznań
country: Poland
facility: Site Reference ID/Investigator # 577
city: Sopot
country: Poland
facility: Site Reference ID/Investigator # 546
city: Warszawa
country: Poland
facility: Site Reference ID/Investigator # 513
city: Wloclawek
country: Poland
facility: Site Reference ID/Investigator # 531
city: Kazan'
country: Russian Federation
facility: Site Reference ID/Investigator # 553
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator # 524
city: Moskva
country: Russian Federation
facility: Site Reference ID/Investigator # 536
city: Novosibirsk
country: Russian Federation
facility: Site Reference ID/Investigator # 515
city: Rostov-na-Donu
country: Russian Federation
facility: Site Reference ID/Investigator # 526
city: Saint Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator # 514
city: Saint Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator # 522
city: Saint Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator # 555
city: Samara
country: Russian Federation
facility: Site Reference ID/Investigator # 523
city: Ufa
country: Russian Federation
facility: Site Reference ID/Investigator # 551
city: Yaroslavl
country: Russian Federation
facility: Site Reference ID/Investigator # 525
city: Belgrade
country: Serbia
facility: Site Reference ID/Investigator # 521
city: Belgrade
country: Serbia
facility: Site Reference ID/Investigator # 575
city: Belgrade
country: Serbia
facility: Site Reference ID/Investigator # 566
city: Kragujevac
country: Serbia
facility: Site Reference ID/Investigator # 500
city: Niš
country: Serbia
facility: Site Reference ID/Investigator # 543
city: Zvezdara
country: Serbia
facility: Site Reference ID/Investigator # 502
city: Chernivtsi
country: Ukraine
facility: Site Reference ID/Investigator # 510
city: Ivano-Frankivs'k
country: Ukraine
facility: Site Reference ID/Investigator # 535
city: Kharkiv
country: Ukraine
facility: Site Reference ID/Investigator # 508
city: Kharkov
country: Ukraine
facility: Site Reference ID/Investigator # 509
city: Kiev
country: Ukraine
facility: Site Reference ID/Investigator # 549
city: Kyiv
country: Ukraine
facility: Site Reference ID/Investigator # 565
city: L'viv
country: Ukraine
facility: Site Reference ID/Investigator # 534
city: Odessa
country: Ukraine
facility: Site Reference ID/Investigator # 520
city: Uzhgorod
country: Ukraine
facility: Site Reference ID/Investigator # 504
city: Vinnytsya
country: Ukraine
facility: Site Reference ID/Investigator # 507
city: Zaporizhzhya
country: Ukraine
facility: Site Reference ID/Investigator # 547
Study officials:
affiliation: Protagonist Therapeutics, Inc.
name: Director Clinical Development
role: STUDY_DIRECTOR
References:
citation: Sandborn WJ, 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 alpha4beta7 Antagonist Peptide: Preclinical Development and Phase 1 and 2a Studies in Ulcerative Colitis. Gastroenterology. 2021 Dec;161(6):1853-1864.e10. doi: 10.1053/j.gastro.2021.08.045. Epub 2021 Aug 30.