A Study to Evaluate the Efficacy and Safety of PF-06480605 in Adults With Moderate to Severe Ulcerative Colitis

Moderate to Severe Ulcerative Colitis Clinical Trial

Official title:

A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate The Efficacy, Safety, and Pharmacokinetics of PF-06480605 in Adult Participants With Moderate To Severe Ulcerative Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04090411
• Other study ID #: B7541007
• Secondary ID: TL1ATuscany 2201
• Status: Completed
• Phase: Phase 2
• Start date: December 19, 2019
• Est. completion date: October 25, 2022

Study information

• Verified date: January 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase 2b study is designed to have all subjects go into a 12 week induction period to compare different doses of study drug against placebo. After induction is complete all subjects will receive active therapy for 40 weeks, followed by a 12 week follow up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 246
• Est. completion date: October 25, 2022
• Est. primary completion date: October 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:-

• A diagnosis of UC for =3 months.
• Participants with moderate to severe active UC as defined by a Total Mayo Score of =6, and an endoscopic subscore of =2.
• Active disease beyond the rectum (>15 cm of active disease from the anal verge at the screening endoscopy).
• Must have failed or been intolerant to at least one of the following class of medications: steroids, immunosuppressants, anti-TNFs, anti-integrin inhibitors, anti- IL-12/23 inhibitors, or JAK inhibitors.

Exclusion Criteria:

• Participants with a diagnosis of ischemic colitis, infectious colitis, radiation colitis, microscopic colitis, indeterminate colitis, or findings suggestive of Crohn's disease (eg, skip lesions, fistulae/perianal disease, non-necrotizing granulomas, etc.).
• Participants with an imminent need for surgery or with elective surgery scheduled to occur during the study
• Chest Radiograph showing abnormalities: The study will accept a Chest x-ray or computed tomography scan of the chest examination performed up to 12 weeks prior to screening if available.
• 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
• Infected with tuberculosis, (TB): Any evidence of untreated latent or active TB infection.
• Infected with human immunodeficiency virus, (HIV), Hepatitis B or C viruses

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Moderate to Severe Ulcerative Colitis
• Ulcer

Intervention

Drug:
• Induction- PF-06480605 50 mg SC Q4W
PF-06480605
• Induction- PF-06480605 150 mg SC Q4W
PF-06480605
• Induction- PF-06480605 450 mg SC Q4W
PF-06480605

Other:
• Induction- Placebo SC Q4W
0 mg Placebo

Drug:
• Chronic- PF-06480605 50 mg SC Q4W
PF-06480605
• Chronic- PF-06480605 150 mg SC Q4W
PF-06480605
• Chronic- PF-06480605 450 mg SC Q4W
PF-06480605

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Mater Misericordiae Ltd.	South Brisbane	Queensland
Belgium	University Hospitals Leuven/Department of Gastroenterology	Leuven
Bulgaria	"ACIBADEM City Clinic Diagnostic-Consultative Center" EOOD	Sofia
Colombia	Asociacion IPS Medicos Internistas de Caldas	Manizales	Caldas
France	CHU d'Amiens-Picardie - SITE SUD	Amiens Cedex 1
France	Centre Hospitalier Regional Universitaire (CHU) de Lille	Lille Cedex
France	Centre Hospitalier Regional Universitaire (CHU) de Lille - CIC	Lille Cedex
France	Centre Hospitalier Regional Universitaire (CHU) de Lille - Hopital Claude Huriez	Lille Cedex
France	CHU Hôtel-Dieu	Nantes Cedex 1
France	Centre Hospitalier Lyon Sud	Pierre-Benite Cedex
France	Centre Hospitalier Universitaire de Lyon Sud	Pierre-Bénite Cedex
Germany	Deutsches Rotes Kreuz Schwesternschaft Berlin Gemeinnützige Krankenhaus GmbH	Berlin
Germany	Studiengesellschaft BSF Unternehmergesellschaft	Halle (Saale)
Germany	Studiengesellschaft BSF UG (haftungsbeschränkt)	Halle/Saale
Hungary	Magyar Imre Kórház	Ajka
Hungary	DRC Gyogyszervizsgalo Kozpont Kft.	Balatonfured	Veszprem
Hungary	Clinexpert Egészségügyi Szolgáltató és Kereskedelmi Kft.	Budapest
Hungary	Life Egészségcentrum	Székesfehérvár
Hungary	Clinfan Kft.	Szekszard
Hungary	Deák Jeno Kórház	Tapolca
Hungary	Clinexpert Tatabanya, Szent Borbala Hospital	Tatabanya
Hungary	Szofia Private Clinic	Veszprém
India	M.S. Ramaiah Medical College and Hospitals	Bangalore	Karnataka
India	M.S. Ramaiah Medical College and Hospitals,	Bangalore,	Karnataka
India	S.M.S. Medical College & Hospital	Jaipur	Rajasthan
India	S.R. Kalla Memorial Gastro & General Hospital	Jaipur	Rajasthan
India	Grant Medical Foundation, Ruby Hall Clinic	Pune	Maharashtra
India	Shree Giriraj Multispeciality Hospital	Rajkot	Gujarat
India	Gujarat Hospital Gastro and Vascular Centre, Opp. Shree Ram Petrol Pump	Surat	Gujarat
India	Surat Institute of Digestive Sciences	Surat	Gujarat
Italy	IRCCS "Saverio de Bellis", UOC Gastroenterologia	Castellana Grotte	Bari
Italy	A.O.U. dell'Università degli Studi della Campania "Luigi Vanvitelli"	Napoli	Naples
Italy	UO Malattie retto-Intestinali Ospedale "Sacro Cuore-don Calabria"	Negrar	Verona
Italy	Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia	Padova
Italy	Policlinico Universitario Campus Bio-Medico di Roma	Roma	RM
Italy	Istituto Clinico Humanitas Centro per le Malattie Infiammatorie Croniche dell'Intestino - IBD Cent	Rozzano	Milan
Japan	Tokyo Medical And Dental University Hospital	Bunkyo-ku	Tokyo
Japan	Fukuoka University Hospital	Fukuoka
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Aichi Medical University Hospital	Nagakute	Aichi
Japan	Toho University Sakura Medical Center	Sakura	Chiba
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	National Hospital Organization Sendai Medical Center	Sendai	Miyagi
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Mexico	Karla Adriana Espinosa Bautista	Ciudad de Mexico
Mexico	BRCR Global Mexico	Guadalajara	Jalisco
Mexico	Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion	Merida	Yucatan
Mexico	Smiq S. de R.L. de C.V.	Queretaro
Poland	KLIMED Marek Klimkiewicz	Bialystok
Poland	Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla	Knurow
Poland	MZ Badania Slowik Zymla Sp. j.	Knurow
Poland	ENDOSKOPIA Sp. z o. o.	Sopot
Poland	Twoja Przychodnia - Szczecinskie Centrum Medyczne	Szczecin
Poland	NZOZ Vivamed Jadwiga Miecz	Warszawa
Poland	WIP Warsaw IBD Point Profesor Kierkus	Warszawa
Poland	Centrum Medyczne Melita Medical	Wroclaw
Romania	Medlife S.A.	Bucuresti
Romania	Spitalul Clinic Colentina	Bucuresti
Russian Federation	KDC "Evromedservis", OJSC	Moscow
Russian Federation	Limited Liability Company "Medicinsky Center SibNovoMed"	Novosibirsk
Russian Federation	LLC Novosibirskiy Gastrocenter	Novosibirsk
Russian Federation	Clinic of OSMU	Omsk
Russian Federation	Perm Clinical Centre of the Federal Medical-Biological Agency	Perm
Russian Federation	Pyatigorsk City Clinical Hospital	Pyatigorsk	Stavropol Region
Russian Federation	Private Healthcare Institution "Clinical Hospital" Russian Railways-Medicine "Samara city"	Samara
Russian Federation	Clinical Hospital named after S.R. Mirotvortsev	Saratov
Russian Federation	Research Institute of Antimicrobial Chemotherapy	Smolensk
Russian Federation	Tomsk Regional Clinical Hospital	Tomsk
Russian Federation	City Hospital JSC "Medical centre"	Tyumen
Russian Federation	SBHI YaR "Regional Clinical Hospital"	Yaroslavl
Serbia	Klinicki Centar Kragujevac	Kragujevac
Serbia	Opsta Bolnica Subotica	Subotica
Serbia	Opsta Bolnica "Djordje Joanovic", Odeljenje Interno, Odsek Gastroenterologija	Zrenjanin
Slovakia	KM Management spol. s.r.o.	Nitra
Slovakia	Gastro LM s.r.o	Presov
Slovakia	ENDOMED, s.r.o.	Vranov nad Toplou
South Africa	Dr van Dyk & Partners Inc	Bloemfontein	FREE State
South Africa	IATROS International	Bloemfontein	FREE State
South Africa	Universitas Private Hospital	Bloemfontein	FREE State
South Africa	Ahmed Kathrada Private Hospital	Johannesburg	Gauteng
South Africa	Lenasia Clinical Trial Centre	Johannesburg	Gauteng
South Africa	Arwyp Medical Centre	Kempton Park	Gauteng
South Africa	Clinresco Centres (Pty) Ltd	Kempton Park	Gauteng
South Africa	Emmed Research	Pretoria	Gauteng
South Africa	Mediclinic Kloof Hospital	Pretoria	Gauteng
South Africa	Radiology24 Jakaranda Hospital	Pretoria	Gauteng
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid
Thailand	Phramongkutklao Hospital	Bangkok
Thailand	Songklanagarind Hospital, Prince of Songkla University	Hat Yai	Songkhla
Thailand	King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University	Pathum Wan	Bangkok
Turkey	Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi	Istanbul
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi	Istanbul
Turkey	Kocaeli Universitesi Tip Fakultesi, Ic Hastaliklari Anabilim Dali	Kocaeli
Turkey	Mersin Universitesi Tip Fakultesi Hastanesi	Mersin
Turkey	Bulent Ecevit Universitesi Tip Fakultesi	Zonguldak
Ukraine	Municipal non-profit enterprise "City clinical hospital #2 named after O.O.Shalimov"	Kharkiv
Ukraine	Municipal non-profit enterprise of Kharkiv regional council "Regional clinical hospital"	Kharkiv
Ukraine	Medical Centre Medical Clinic Blagomed LLC	Kyiv
Ukraine	Municipal Non-profit Enterprise "Kyiv City Clinical Hospital #1"	Kyiv
Ukraine	Municipal non-profit enterprise of Kyiv regional council "Kyiv regional clinical hospital"	Kyiv
Ukraine	Municipal Non-profit enterprise of Kyiv Regional Council "Kyiv regional hospital"	Kyiv
Ukraine	Medical center of Limited Liability Company "Health Clinic", medical clinical research center	Vinnytsia
Ukraine	Medical Centre "DIACENTER" LLC	Zaporizhzhia
United Kingdom	MeDiNova Northamptonshire Quality Research Site	Corby
United Kingdom	Egin Research Ltd	High Wycombe
United Kingdom	Chest X-ray Facility - BMI Bishops Wood Hospital	Northwood
United Kingdom	MeDiNova North London Quality Research Site	Northwood	Middlesex
United Kingdom	Spire Nottingham Hospital	Nottingham
United Kingdom	Endoscopy Facility - Orpington Endoscopy Centre	Orpington
United Kingdom	Endoscopy Facility - Spire Little Aston Hospital	Sutton Coldfield	Birmingham
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Brigham and Women's Hospital - Office	Boston	Massachusetts
United States	Medycal Research Inc.	Brooksville	Florida
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	The University of Chicago Medical Center (clinic address)	Chicago	Illinois
United States	Safety Harbor Surgery	Clearwater	Florida
United States	Trident Care	Clearwater	Florida
United States	Digestive Health Specialists	Dothan	Alabama
United States	Dothan Surgery Center	Dothan	Alabama
United States	Flowers Hospital	Dothan	Alabama
United States	Gastroenterology Associates of Northern VA	Fairfax	Virginia
United States	Gastroenterology Associates of Northern Virginia	Fairfax	Virginia
United States	Verity Research, Inc.	Fairfax	Virginia
United States	Michigan Endoscopy Center	Farmington Hills	Michigan
United States	Gastroenterology Associates, PA of Greenville	Greenville	South Carolina
United States	Endoscopy Center of Connecticut, LLC	Guilford	Connecticut
United States	Endoscopy Center of Connecticut, LLC	Hamden	Connecticut
United States	Medical Research Center Of Connecticut, LLC	Hamden	Connecticut
United States	PACT Gastroenterology Center	Hamden	Connecticut
United States	Whitney Imaging	Hamden	Connecticut
United States	PrimeCare Medical Group	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Sierra Clinical Research	Las Vegas	Nevada
United States	Valley View Surgery Center	Las Vegas	Nevada
United States	Lynn Institute of the Ozarks	Little Rock	Arkansas
United States	Vanderbilt GI Endoscopy Lab at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt Heart One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt Inflammatory Bowel Disease Clinic	Nashville	Tennessee
United States	Vanderbilt Laboratory Services North One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt One Hundred Oaks Imaging	Nashville	Tennessee
United States	Vanderbilt University Med. Center	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Vanderbilt University Medical Center - GI Research Office	Nashville	Tennessee
United States	Vanderbilt University Medical Center- Heart Station (ECG)	Nashville	Tennessee
United States	New York Presbyterian Hospital - Weill Cornell Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	Weill Cornell Medical College- New York Presbyterian Hospital	New York	New York
United States	Surinder Saini, M.D., Inc.	Newport Beach	California
United States	Tower Radiology Center	Oldsmar	Florida
United States	Investigational Drug Services	Philadelphia	Pennsylvania
United States	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Gastroenterology Consultants P.C.	Roswell	Georgia
United States	Gastroenterology Consultants of San Antonio, PA	San Antonio	Texas
United States	South Texas Radiology Imaging Centers	San Antonio	Texas
United States	VIP Trials	San Antonio	Texas
United States	Akumin	Tampa	Florida
United States	Alliance Clinical Research of Tampa	Tampa	Florida
United States	Tampa Bay Endoscopy Center	Tampa	Florida
United States	Allegiance Internal Medicine and Allegiance Research Specialists	Wauwatosa	Wisconsin
United States	GI Associates	Wauwatosa	Wisconsin
United States	Medical Diagnostic Imaging	Wauwatosa	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Colombia,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Mexico,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants achieving clinical remission (defined as a Total Mayo Score =2, with no individual subscore >1) at Week 14. Safety and tolerability will also be assessed		week 0-14
Primary	Incidence and severity of treatment emergent adverse events (TEAEs) during the induction period.		week 0-14
Primary	Incidence of serious adverse events (SAEs) during the induction period.		week 0-14
Primary	Incidence of AEs or SAEs leading to discontinuation during the induction period.		week 0-14
Primary	Incidence of clinically significant abnormalities in vital signs, electrocaridograms, (ECGs) and laboratory values during the induction period.		week 0-14
Primary	Incidence and severity of treatment emergent adverse events (TEAEs) during the chronic therapy period.		Weeks 14-64
Primary	Incidence of serious adverse events (SAEs) during the chronic therapy period.		Weeks 14-64
Primary	Incidence of AEs or SAEs leading to discontinuation during the chronic therapy period.		Weeks 14-64
Primary	Incidence of clinically significant abnormalities in vital signs, ECGs and laboratory values during the chronic therapy period.		Weeks 14-64
Secondary	Proportion of participants achieving remission Food and Drug Administration, ((FDA) definition 1 - defined as endoscopic subscore = 0 or 1, stool frequency subscore = 0, and rectal bleeding subscore = 0) at Week 14.		week 0-14
Secondary	Proportion of participants achieving remission (FDA definition 2 - defined as endoscopic subscore = 0 or 1, =1 point decrease from baseline to achieve a stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0) at Week 14.		week 0-14
Secondary	Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 14.		week 0-14
Secondary	Proportion of participants achieving endoscopic remission (defined as endoscopic subscore = 0) at Week 14.		week 0-14
Secondary	PF 06480605 trough concentrations during the induction period through Week 14.		week 0-14
Secondary	Change from baseline in fecal calprotectin during the induction period through Week 14.		week 0-14
Secondary	Change from baseline in hsCRP during the induction period through Week 14.		week 0-14
Secondary	Change from baseline in serum sTL1A during the induction period through Week 14.		week 0-14
Secondary	Incidence of development of anti drug antibodies (ADAs) and neutralizing antibodies (NAbs) during the induction period through Week 14.		week 0-14
Secondary	Proportion of participants achieving clinical remission (defined as a Total Mayo Score >/= to 2, with no individual subscore >1) at Week 56.		Weeks 14-56
Secondary	Proportion of participants achieving sustained clinical remission (ie, clinical remission at both Week 14 and Week 56).		Weeks 14-56
Secondary	Proportion of participants achieving remission (FDA definition 1 - defined as endoscopic subscore = 0 or 1, stool frequency subscore = 0, and rectal bleeding subscore = 0) at Week 56.		Weeks 14-56
Secondary	Proportion of participants achieving sustained remission-FDA definition 1 (ie, remission-FDA definition 1 at both Week 14 and Week 56).		Weeks 14-56
Secondary	Proportion of participants achieving sustained remission-FDA definition 2 (ie, remission-FDA definition 2 at both Week 14 and Week 56).		Weeks 14-56
Secondary	Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 56.		Weeks 14-56
Secondary	Proportion of participants achieving sustained endoscopic improvement (ie, endoscopic improvement at both Week 14 and Week 56).		Weeks 14-56
Secondary	Proportion of participants achieving endoscopic remission (defined as endoscopic sub-score = 0) at Week 56.		Weeks 14-56
Secondary	Proportion of participants achieving sustained endoscopic remission (ie, endoscopic remission at both Week 14 and Week 56).		Weeks 14-56
Secondary	PF-06480605 concentration from Week 14 through the End of Study Visit.		Weeks 14-64
Secondary	Change from Week 14 in fecal calprotectin during the chronic therapy period through the End of Study Visit		Weeks 14-64
Secondary	Change from Week 14 in hsCRP during the chronic therapy period through the End of Study Visit.		Weeks 14-64
Secondary	Change from week 14 in serum sTL1A during the chronic therapy period through the End of Study Visit.		Weeks 14-64
Secondary	Change from baseline through the End of the Study Visit in fecal calprotectin		weeks 14-64
Secondary	Change from baseline through the End of the Study Visit in hsCRP.		Weeks 14-64
Secondary	Change from baseline through the End of Study Visit in serum sTL1A.		Weeks 14-64
Secondary	Incidence of development of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) from Week 14 through the End of Study Visit.		Weeks 14-64

External Links

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