PN-943 in Adults With Moderate to Severe Active Ulcerative Colitis (UC)

Ulcerative Colitis Chronic Moderate Clinical Trial

Official title:

A Phase 2 Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-center Study to Evaluate the Safety and Efficacy of Oral PN-943 in Subjects With Moderate to Severe Active Ulcerative Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04504383
• Other study ID #: PN-943-03
• Status: Completed
• Phase: Phase 2
• Start date: August 5, 2020
• Est. completion date: February 16, 2023

Study information

• Verified date: April 2023
• Source: Protagonist Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the safety, tolerability, and clinical efficacy of PN-943 450 mg twice daily [BID] and PN-943 150 mg BID, compared with placebo BID, in subjects with moderate to severe active Ulcerative Colitis (UC).

Description:

The study consists of a 12-week double-blind, placebo-controlled treatment period. Participants will be randomized in a 1:1:1 ratio to PN-943 450 mg BID, PN-943 150 mg BID, or matching placebo BID. Participants who successfully complete the double-blind period may be eligible for an extended treatment period of 40 weeks duration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 169
• Est. completion date: February 16, 2023
• Est. primary completion date: February 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

1. Male and female subjects age 18 (or the minimum country specific age of consent if >18) to 75 years.

2. Subject understands the study procedures and agrees to participate in the study by giving written informed consent.

3. Diagnosis of UC supported by appropriate documentation of biopsy results consistent with UC.

4. Moderate to severe active UC.

5. Demonstrated inadequate response, loss of response, or intolerance of at least 1 of oral aminosalicylates (5-ASAs), corticosteroids, immunomodulators, or a biologic (excluding vedolizumab).

Key Exclusion Criteria:

1. Subject with a current diagnosis of Crohn's disease (CD), indeterminate colitis (IC), microscopic colitis, ischemic colitis, radiation colitis.

2. History of colonic dysplasia other than completely removed low-grade dysplastic lesion.

3. History of active bacterial, viral, fungal or mycobacterial infection requiring hospitalization or IV antibiotic/anti-infective treatment within 4 weeks of screening or oral antibiotics/anti-infectives within 2 weeks of screening.

4. Prior treatment with vedolizumab, natalizumab, or any agent targeting the a4ß7 or ß1 integrin or planned during the study.

5. Positive stool test for C. difficile.

6. Chronic recurrent or serious infection.

7. Known primary or secondary immunodeficiency.

8. Pregnant or lactating female or considering becoming pregnant during the study or within 30 days after the last dose of study medication.

9. History of any major neurological disorders.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis Chronic Moderate
• Ulcerative Colitis Chronic Severe

Intervention

Drug:
• PN-943
Administered by the oral route BID for the duration of the study.
• Placebo
Administered by the oral route BID for 12 weeks.

Locations

Country	Name	City	State
Austria	Protagonist Investigational Site	Innsbruck
Austria	Protagonist Investigational Site	Salzburg
Austria	Protagonist Investigational Site	Vienna
Bulgaria	Protagonist Investigational Site	Sofia
Bulgaria	Protagonist Investigational Site	Sofia
Canada	Protagonist Investigational Site	Kelowna	British Columbia
Canada	Protagonist Investigational Site	North Bay	Ontario
Canada	Protagonist Investigational Site	Toronto	Ontario
Canada	Protagonist Investigational Site	Vancouver	British Columbia
Canada	Protagonist Investigational Site	Vaughan	Ontario
Canada	Protagonist Investigational Site	West Vancouver	British Columbia
Georgia	Protagonist Investigational Site	Tbilisi
Georgia	Protagonist Investigational Site	Tbilisi
Georgia	Protagonist Investigational Site	Tbilisi
Georgia	Protagonist Investigational Site	Tbilisi
Georgia	Protagonist Investigational Site	Tbilisi
Germany	Protagonist Investigational Site	Berlin
Germany	Protagonist Investigational Site	Berlin
Germany	Protagonist Investigational Site	Kiel
Germany	Protagonist Investigational Site	Tuebingen
Hungary	Protagonist Investigational Site	Budapest
Hungary	Protagonist Investigational Site	Debrecen
Hungary	Protagonist Investigational Site	Székesfehérvár
Italy	Protagonist Investigational Site	Castellana Grotte
Italy	Protagonist Investigational Site	Modena
Italy	Protagonist Investigational Site	Negrar
Italy	Protagonist Investigational Site	Padova
Italy	Protagonist Investigational Site	Roma
Italy	Protagonist Investigational Site	Roma
Italy	Protagonist Investigational Site	San Giovanni Rotondo
Korea, Republic of	Protagonist Investigational Site	Busan
Korea, Republic of	Protagonist Investigational Site	Busan
Korea, Republic of	Protagonist Investigational Site	Daegu
Korea, Republic of	Protagonist Investigational Site	Daegu
Korea, Republic of	Protagonist Investigational Site	Daejeon
Korea, Republic of	Protagonist Investigational Site	Seoul
Korea, Republic of	Protagonist Investigational Site	Seoul
Korea, Republic of	Protagonist Investigational site	Seoul
Poland	Protagonist Investigational Site	Bydgoszcz
Poland	Protagonist Investigational Site	Bydgoszcz
Poland	Protagonist Investigational Site	Czestochowa
Poland	Protagonist Investigational Site	Czestochowa
Poland	Protagonist Investigational Site	Katowice
Poland	Protagonist Investigational Site	Kraków
Poland	Protagonist Investigational Site	Ksawerów
Poland	Protagonist Investigational Site	Lódz
Poland	Protagonist Investigational Site	Lódz
Poland	Protagonist Investigational Site	Lublin
Poland	Protagonist Investigational Site	Nowy Targ
Poland	Protagonist Investigational Site	Piotrków Trybunalski
Poland	Protagonist Investigational Site	Poznan
Poland	Protagonist Investigational Site	Poznan
Poland	Protagonist Investigational Site	Poznan	Wielkopolskie
Poland	Protagonist Investigational Site	Rzeszów
Poland	Protagonist Investigational Site	Sopot
Poland	Protagonist Investigational Site	Swidnica
Poland	Protagonist Investigational Site	Torun
Poland	Protagonist Investigational Site	Tychy
Poland	Protagonist Investigational Site	Warsaw
Poland	Protagonist Investigational Site	Warsaw
Poland	Protagonist Investigational Site	Warszawa
Poland	Protagonist Investigational Site	Wloclawek
Poland	Protagonist Investigational Site	Wroclaw
Poland	Protagonist Investigational Site	Wroclaw
Poland	Protagonist Investigational Site	Wroclaw
Poland	Protagonist Investigational Site	Wroclaw
Russian Federation	Protagonist Investigational Site	Chelyabinsk
Russian Federation	Protagonist Investigational Site	Moscow
Russian Federation	Protagonist Investigational Site	Novosibirsk
Russian Federation	Protagonist Investigational Site	Novosibirsk
Russian Federation	Protagonist Investigational Site	Perm
Russian Federation	Protagonist Investigational Site	Pyatigorsk
Russian Federation	Protagonist Investigational Site	Saint Petersburg
Russian Federation	Protagonist Investigational Site	Saint Petersburg
Russian Federation	Protagonist Investigational Site	Saint Petersburg
Russian Federation	Protagonist Investigational Site	Saint Petersburg
Russian Federation	Protagonist Investigational Site	Samara
Russian Federation	Protagonist Investigational Site	Saratow
Russian Federation	Protagonist Investigational Site	Stavropol'
Russian Federation	Protagonist Investigational Site	Tomsk
Russian Federation	Protagonist Investigational Site	Tyumen
Serbia	Protagonist Investigational Site	Zrenjanin
Ukraine	Protagonist Investigational Site	Ivano-Frankivs'k
Ukraine	Protagonist Investigational Site	Kherson
Ukraine	Protagonist Investigational Site	Kyiv
Ukraine	Protagonist Investigational Site	Kyiv
Ukraine	Protagonist Investigational Site	Kyiv
Ukraine	Protagonist Investigational Site	Lviv
Ukraine	Protagonist Investigational Site	Vinnytsia
Ukraine	Protagonist Investigational Site	Vinnytsia
Ukraine	Protagonist Investigational Site	Zhytomyr
United States	Protagonist Investigational Site	Austin	Texas
United States	Protagonist Investigational Site	Charlotte	North Carolina
United States	Protagonist Investigational Site	Chesterfield	Michigan
United States	Protagonist Investigational Site	Colorado Springs	Colorado
United States	Protagonist Investigational Site	Englewood	New Jersey
United States	Protagonist Investigational Site	Garden Grove	California
United States	Protagonist Investigational site	Garland	Texas
United States	Protagonist Investigational Site	Glen Burnie	Maryland
United States	Protagonist Investigational Site	Jackson	Mississippi
United States	Protagonist Investigational Site	Kissimmee	Florida
United States	Protagonist Investigational Site	Los Angeles	California
United States	Protagonist Investigational site	Lynchburg	Virginia
United States	Protagonist Investigational Site	Metairie	Louisiana
United States	Protagonist Investigational Site	Miami	Florida
United States	Protagonist Investigational Site	Miami	Florida
United States	Protagonist Investigational Site	Miami	Florida
United States	Protagonist Investigational Site	Murrieta	California
United States	Protagonist Investigational Site	Nashville	Tennessee
United States	Protagonist Investigational Site	Norman	Oklahoma
United States	Protagonist Investigational Site	North Massapequa	New York
United States	Protagonist Investigational Site	Oklahoma City	Oklahoma
United States	Protagonist Investigational Site	Orangeburg	South Carolina
United States	Protagonist Investigational site	Orlando	Florida
United States	Protagonist Investigational Site	Pasadena	Texas
United States	Protagonist Investigational Site	Saint Augustine	Florida
United States	Protagonist Investigational Site	Saint Louis	Missouri
United States	Protagonist Investigational Site	San Francisco	California
United States	Protagonist Investigational Site	Spring	Texas
United States	Protagonist Investigational Site	Troy	Michigan
United States	Protagonist Investigational Site	Tucson	Arizona
United States	Protagonist Investigational Site	Wesley Chapel	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Protagonist Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Bulgaria,  Canada,  Georgia,  Germany,  Hungary,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of subjects achieving clinical remission at Week 52.	Clinical remission is determined using the Adapted Mayo score (sum of 3 subscores from the Mayo score): Stool frequency subscore (SFS); Rectal bleeding subscore (RBS); Endoscopic subscore (ESS)	Week 52
Primary	Proportion of subjects achieving clinical remission at Week 12 compared to placebo.	Clinical remission is determined using the Adapted Mayo score (sum of 3 subscores from the Mayo score): Stool frequency subscore (SFS); Rectal bleeding subscore (RBS); Endoscopic subscore (ESS)	Week 12
Secondary	Comparison between PN-943 high-dose and low-dose individually to placebo.	Proportion of subjects with endoscopic improvement.; Proportion of subjects achieving endoscopic remission.; Proportion of subjects with histological improvement.; Proportion of subjects achieving histological remission.; Proportion of subjects with mucosal healing.	Week 12