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

Ulcerative Colitis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02895100
• Other study ID #: PTG-100-02
• Status: Terminated
• Phase: Phase 2
• Start date: December 2016
• Est. completion date: March 26, 2018

Study information

• Verified date: September 2021
• Source: Protagonist Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 98
• Est. completion date: March 26, 2018
• Est. primary completion date: March 26, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• PTG-100
Daily dosing of PTG-100 by subject for a 12 week treatment period.
• Placebo
Daily dosing of Placebo capsules by subject for a 12 week treatment period.

Locations

Country	Name	City	State
Australia	Site Reference ID/Investigator # 908	Herston
Australia	Site Reference ID/Investigator # 901	Murdoch	Western Australia
Australia	Site Reference ID/Investigator # 900	South Brisbane
Australia	Site Reference ID/Investigator # 907	Subiaco
Belgium	Site Reference ID/Investigator # 559	Gent
Belgium	Site Reference ID/Investigator # 533	Kortrijk
Belgium	Site Reference ID/Investigator # 505	Leuven
Bosnia and Herzegovina	Site Reference ID/Investigator # 573	Mostar
Bosnia and Herzegovina	Site Reference ID/Investigator # 571	Tuzla
Canada	Site Reference ID/Investigator # 105	London	Ontario
Canada	Site Reference ID/Investigator # 103	Vancouver	British Columbia
Croatia	Site Reference ID/Investigator #556	Osijek
Croatia	Site Reference ID/Investigator # 550	Split
Croatia	Site Reference ID/Investigator # 562	Zagreb
Czechia	Site Reference ID/Investigator # 517	Nový Hradec Králové
Czechia	Site Reference ID/Investigator # 539	Zlín
Germany	Site Reference ID/Investigator # 542	Berlin
Germany	Site Reference ID/Investigator # 560	Berlin
Germany	Site Reference ID/Investigator # 532	Kiel
Germany	Site Reference ID/Investigator # 506	Leipzig
Germany	Site Reference ID/Investigator # 572	Mannheim
Germany	Site Reference ID/Investigator # 538	Münster
Germany	Site Reference ID/Investigator # 574	Tuebingen
Germany	Site Reference ID/Investigator # 541	Ulm
Hungary	Site Reference ID/Investigator # 554	Budapest
Hungary	Site Reference ID/Investigator # 558	Budapest
Hungary	Site Reference ID/Investigator # 552	Debrecen
Hungary	Site Reference ID/Investigator # 567	Eger
Hungary	Site Reference ID/Investigator # 557	Kistarcsa
Hungary	Site Reference ID/Investigator # 544	Mosonmagyaróvár
Hungary	Site Reference ID/Investigator # 563	Sopron
Korea, Republic of	Site Reference ID/Investigator # 906	Daegu
Korea, Republic of	Site Reference ID/Investigator # 904	Seoul
Korea, Republic of	Site Reference ID/Investigator # 905	Seoul
Latvia	Site Reference ID/Investigator # 501	Riga
Latvia	Site Reference ID/Investigator # 545	Riga
Netherlands	Site Reference ID/Investigator # 568	Amsterdam
New Zealand	Site Reference ID/Investigator # 903	Dunedin
New Zealand	Site Reference ID/Investigator # 902	Newton
Poland	Site Reference ID/Investigator # 529	Kielce
Poland	Site Reference ID/Investigator # 540	Krakow
Poland	Site Reference ID/Investigator # 576	Kraków
Poland	Site Reference ID/Investigator # 512	Ksawerów
Poland	Site Reference ID/Investigator # 518	Lodz
Poland	Site Reference ID/Investigator # 530	Lodz
Poland	Site Reference ID/Investigator # 577	Poznan
Poland	Site Reference ID/Investigator # 546	Sopot
Poland	Site Reference ID/Investigator # 513	Warszawa
Poland	Site Reference ID/Investigator # 531	Wloclawek
Russian Federation	Site Reference ID/Investigator # 553	Kazan'
Russian Federation	Site Reference ID/Investigator # 524	Moscow
Russian Federation	Site Reference ID/Investigator # 536	Moskva
Russian Federation	Site Reference ID/Investigator # 515	Novosibirsk
Russian Federation	Site Reference ID/Investigator # 526	Rostov-na-Donu
Russian Federation	Site Reference ID/Investigator # 514	Saint Petersburg
Russian Federation	Site Reference ID/Investigator # 522	Saint Petersburg
Russian Federation	Site Reference ID/Investigator # 555	Saint Petersburg
Russian Federation	Site Reference ID/Investigator # 523	Samara
Russian Federation	Site Reference ID/Investigator # 551	Ufa
Russian Federation	Site Reference ID/Investigator # 525	Yaroslavl
Serbia	Site Reference ID/Investigator # 521	Belgrade
Serbia	Site Reference ID/Investigator # 566	Belgrade
Serbia	Site Reference ID/Investigator # 575	Belgrade
Serbia	Site Reference ID/Investigator # 500	Kragujevac
Serbia	Site Reference ID/Investigator # 543	Niš
Serbia	Site Reference ID/Investigator # 502	Zvezdara
Ukraine	Site Reference ID/Investigator # 510	Chernivtsi
Ukraine	Site Reference ID/Investigator # 535	Ivano-Frankivs'k
Ukraine	Site Reference ID/Investigator # 508	Kharkiv
Ukraine	Site Reference ID/Investigator # 509	Kharkov
Ukraine	Site Reference ID/Investigator # 549	Kiev
Ukraine	Site Reference ID/Investigator # 565	Kyiv
Ukraine	Site Reference ID/Investigator # 534	L'viv
Ukraine	Site Reference ID/Investigator # 520	Odessa
Ukraine	Site Reference ID/Investigator # 504	Uzhgorod
Ukraine	Site Reference ID/Investigator # 507	Vinnytsya
Ukraine	Site Reference ID/Investigator # 547	Zaporizhzhya
United States	Site Reference ID/Investigator # 100	Atlanta	Georgia
United States	Site Reference ID/Investigator # 126	Bastrop	Louisiana
United States	Site Reference ID/Investigator # 117	Chevy Chase	Maryland
United States	Site Reference ID/Investigator # 107	Chicago	Illinois
United States	Site Reference ID/Investigator # 119	Cincinnati	Ohio
United States	Site Reference ID/Investigator # 125	Colorado Springs	Colorado
United States	Site Reference ID/Investigator # 118	DeSoto	Texas
United States	Site Reference ID/Investigator # 109	Great Neck	New York
United States	Site Reference ID/Investigator # 110	Hermitage	Tennessee
United States	Site Reference ID/Investigator # 101	Los Angeles	California
United States	Site Reference ID/Investigator # 102	Los Angeles	California
United States	Site Reference ID/Investigator # 104	Marietta	Georgia
United States	Site Reference ID/Investigator # 120	Miami	Florida
United States	Site Reference ID/Investigator # 128	Nashville	Tennessee
United States	Site Reference ID/Investigator # 122	New York	New York
United States	Site Reference ID/Investigator # 106	Port Orange	Florida
United States	Site Reference ID/Investigator # 113	Richmond	Virginia
United States	Site Reference ID/Investigator # 115	Saint Augustine	Florida
United States	Site Reference ID/Investigator # 114	Shreveport	Louisiana
United States	Site Reference ID/Investigator # 112	Suwanee	Georgia
United States	Site Reference ID/Investigator # 116	Sweetwater	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Protagonist Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bosnia and Herzegovina,  Canada,  Croatia,  Czechia,  Germany,  Hungary,  Korea, Republic of,  Latvia,  Netherlands,  New Zealand,  Poland,  Russian Federation,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Subjects Receiving PTG-100 With Clinical Remission at Week 12 Compared With Placebo	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.	12 week treatment period