Clinical trial NCT04090411: A Study to Evaluate the Efficacy and Safety of PF-06480605 in Adults With Moderate to Severe Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Moderate to Severe Ulcerative Colitis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2019-09-16
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: week 0-14
measure: Incidence and severity of treatment emergent adverse events (TEAEs) during the induction period.
timeFrame: week 0-14
measure: Incidence of serious adverse events (SAEs) during the induction period.
timeFrame: week 0-14
measure: Incidence of AEs or SAEs leading to discontinuation during the induction period.
timeFrame: week 0-14
measure: Incidence of clinically significant abnormalities in vital signs, electrocaridograms, (ECGs) and laboratory values during the induction period.
timeFrame: week 0-14
measure: Incidence and severity of treatment emergent adverse events (TEAEs) during the chronic therapy period.
timeFrame: Weeks 14-64
measure: Incidence of serious adverse events (SAEs) during the chronic therapy period.
timeFrame: Weeks 14-64
measure: Incidence of AEs or SAEs leading to discontinuation during the chronic therapy period.
timeFrame: Weeks 14-64
measure: Incidence of clinically significant abnormalities in vital signs, ECGs and laboratory values during the chronic therapy period.
timeFrame: Weeks 14-64
Secondary outcomes:
measure: 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.
timeFrame: week 0-14
measure: 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.
timeFrame: week 0-14
measure: Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 14.
timeFrame: week 0-14
measure: Proportion of participants achieving endoscopic remission (defined as endoscopic subscore = 0) at Week 14.
timeFrame: week 0-14
measure: PF 06480605 trough concentrations during the induction period through Week 14.
timeFrame: week 0-14
measure: Change from baseline in fecal calprotectin during the induction period through Week 14.
timeFrame: week 0-14
measure: Change from baseline in hsCRP during the induction period through Week 14.
timeFrame: week 0-14
measure: Change from baseline in serum sTL1A during the induction period through Week 14.
timeFrame: week 0-14
measure: Incidence of development of anti drug antibodies (ADAs) and neutralizing antibodies (NAbs) during the induction period through Week 14.
timeFrame: week 0-14
measure: Proportion of participants achieving clinical remission (defined as a Total Mayo Score >/= to 2, with no individual subscore >1) at Week 56.
timeFrame: Weeks 14-56
measure: Proportion of participants achieving sustained clinical remission (ie, clinical remission at both Week 14 and Week 56).
timeFrame: Weeks 14-56
measure: 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.
timeFrame: Weeks 14-56
measure: Proportion of participants achieving sustained remission-FDA definition 1 (ie, remission-FDA definition 1 at both Week 14 and Week 56).
timeFrame: Weeks 14-56
measure: Proportion of participants achieving sustained remission-FDA definition 2 (ie, remission-FDA definition 2 at both Week 14 and Week 56).
timeFrame: Weeks 14-56
measure: Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 56.
timeFrame: Weeks 14-56
measure: Proportion of participants achieving sustained endoscopic improvement (ie, endoscopic improvement at both Week 14 and Week 56).
timeFrame: Weeks 14-56
measure: Proportion of participants achieving endoscopic remission (defined as endoscopic sub-score = 0) at Week 56.
timeFrame: Weeks 14-56
measure: Proportion of participants achieving sustained endoscopic remission (ie, endoscopic remission at both Week 14 and Week 56).
timeFrame: Weeks 14-56
measure: PF-06480605 concentration from Week 14 through the End of Study Visit.
timeFrame: Weeks 14-64
measure: Change from Week 14 in fecal calprotectin during the chronic therapy period through the End of Study Visit
timeFrame: Weeks 14-64
measure: Change from Week 14 in hsCRP during the chronic therapy period through the End of Study Visit.
timeFrame: Weeks 14-64
measure: Change from week 14 in serum sTL1A during the chronic therapy period through the End of Study Visit.
timeFrame: Weeks 14-64
measure: Change from baseline through the End of the Study Visit in fecal calprotectin
timeFrame: weeks 14-64
measure: Change from baseline through the End of the Study Visit in hsCRP.
timeFrame: Weeks 14-64
measure: Change from baseline through the End of Study Visit in serum sTL1A.
timeFrame: Weeks 14-64
measure: Incidence of development of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) from Week 14 through the End of Study Visit.
timeFrame: Weeks 14-64
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists
state: Alabama
city: Dothan
country: United States
facility: Dothan Surgery Center
state: Alabama
city: Dothan
country: United States
facility: Flowers Hospital
state: Alabama
city: Little Rock
country: United States
facility: Lynn Institute of the Ozarks
state: Arkansas
city: Newport Beach
country: United States
facility: Surinder Saini, M.D., Inc.
state: California
city: Guilford
country: United States
facility: Endoscopy Center of Connecticut, LLC
state: Connecticut
city: Hamden
country: United States
facility: Endoscopy Center of Connecticut, LLC
state: Connecticut
city: Hamden
country: United States
facility: Medical Research Center Of Connecticut, LLC
state: Connecticut
city: Hamden
country: United States
facility: PACT Gastroenterology Center
state: Connecticut
city: Hamden
country: United States
facility: Whitney Imaging
state: Connecticut
city: Brooksville
country: United States
facility: Medycal Research Inc.
state: Florida
city: Clearwater
country: United States
facility: Safety Harbor Surgery
state: Florida
city: Clearwater
country: United States
facility: Trident Care
state: Florida
city: Oldsmar
country: United States
facility: Tower Radiology Center
state: Florida
city: Tampa
country: United States
facility: Akumin
state: Florida
city: Tampa
country: United States
facility: Tampa Bay Endoscopy Center
state: Florida
city: Tampa
country: United States
facility: Alliance Clinical Research of Tampa
state: Florida
city: Roswell
country: United States
facility: Gastroenterology Consultants P.C.
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medical Center (clinic address)
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital - Office
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Farmington Hills
country: United States
facility: Michigan Endoscopy Center
state: Michigan
city: Las Vegas
country: United States
facility: Valley View Surgery Center
state: Nevada
city: Las Vegas
country: United States
facility: Sierra Clinical Research
state: Nevada
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College- New York Presbyterian Hospital
state: New York
city: Philadelphia
country: United States
facility: Investigational Drug Services
state: Pennsylvania
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Greenville
country: United States
facility: Gastroenterology Associates, PA of Greenville
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt GI Endoscopy Lab at One Hundred Oaks
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Heart One Hundred Oaks
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Inflammatory Bowel Disease Clinic
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Laboratory Services North One Hundred Oaks
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt One Hundred Oaks Imaging
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center - GI Research Office
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Med. Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center- Heart Station (ECG)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: PrimeCare Medical Group
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Consultants of San Antonio, PA
state: Texas
city: San Antonio
country: United States
facility: VIP Trials
state: Texas
city: San Antonio
country: United States
facility: South Texas Radiology Imaging Centers
state: Texas
city: Fairfax
country: United States
facility: Gastroenterology Associates of Northern VA
state: Virginia
city: Fairfax
country: United States
facility: Gastroenterology Associates of Northern Virginia
state: Virginia
city: Fairfax
country: United States
facility: Verity Research, Inc.
state: Virginia
city: Wauwatosa
country: United States
facility: Medical Diagnostic Imaging
state: Wisconsin
city: Wauwatosa
country: United States
facility: Allegiance Internal Medicine and Allegiance Research Specialists
state: Wisconsin
city: Wauwatosa
country: United States
facility: GI Associates
state: Wisconsin
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd.
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Leuven
country: Belgium
facility: University Hospitals Leuven/Department of Gastroenterology
city: Sofia
country: Bulgaria
facility: "ACIBADEM City Clinic Diagnostic-Consultative Center" EOOD
city: Manizales
country: Colombia
facility: Asociacion IPS Medicos Internistas de Caldas
state: Caldas
city: Amiens Cedex 1
country: France
facility: CHU d'Amiens-Picardie - SITE SUD
city: Lille Cedex
country: France
facility: Centre Hospitalier Regional Universitaire (CHU) de Lille - CIC
city: Lille Cedex
country: France
facility: Centre Hospitalier Regional Universitaire (CHU) de Lille - Hopital Claude Huriez
city: Lille Cedex
country: France
facility: Centre Hospitalier Regional Universitaire (CHU) de Lille
city: Nantes Cedex 1
country: France
facility: CHU Hôtel-Dieu
city: Pierre-Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Pierre-Bénite Cedex
country: France
facility: Centre Hospitalier Universitaire de Lyon Sud
city: Berlin
country: Germany
facility: Deutsches Rotes Kreuz Schwesternschaft Berlin Gemeinnützige Krankenhaus GmbH
city: Halle (Saale)
country: Germany
facility: Studiengesellschaft BSF Unternehmergesellschaft
city: Halle/Saale
country: Germany
facility: Studiengesellschaft BSF UG (haftungsbeschränkt)
city: Balatonfured
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft.
state: Veszprem
city: Ajka
country: Hungary
facility: Magyar Imre Kórház
city: Budapest
country: Hungary
facility: Clinexpert Egészségügyi Szolgáltató és Kereskedelmi Kft.
city: Szekszard
country: Hungary
facility: Clinfan Kft.
city: Székesfehérvár
country: Hungary
facility: Life Egészségcentrum
city: Tapolca
country: Hungary
facility: Deák Jenő Kórház
city: Tatabanya
country: Hungary
facility: Clinexpert Tatabanya, Szent Borbala Hospital
city: Veszprém
country: Hungary
facility: Szofia Private Clinic
city: Rajkot
country: India
facility: Shree Giriraj Multispeciality Hospital
state: Gujarat
city: Surat
country: India
facility: Surat Institute of Digestive Sciences
state: Gujarat
city: Surat
country: India
facility: Gujarat Hospital Gastro and Vascular Centre, Opp. Shree Ram Petrol Pump
state: Gujarat
city: Bangalore,
country: India
facility: M.S. Ramaiah Medical College and Hospitals,
state: Karnataka
city: Bangalore
country: India
facility: M.S. Ramaiah Medical College and Hospitals
state: Karnataka
city: Pune
country: India
facility: Grant Medical Foundation, Ruby Hall Clinic
state: Maharashtra
city: Jaipur
country: India
facility: S.R. Kalla Memorial Gastro & General Hospital
state: Rajasthan
city: Jaipur
country: India
facility: S.M.S. Medical College & Hospital
state: Rajasthan
city: Castellana Grotte
country: Italy
facility: IRCCS "Saverio de Bellis", UOC Gastroenterologia
state: Bari
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas Centro per le Malattie Infiammatorie Croniche dell'Intestino - IBD Cent
state: Milan
city: Napoli
country: Italy
facility: A.O.U. dell'Università degli Studi della Campania "Luigi Vanvitelli"
state: Naples
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico di Roma
state: RM
city: Negrar
country: Italy
facility: UO Malattie retto-Intestinali Ospedale "Sacro Cuore-don Calabria"
state: Verona
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova - U.O.C. di Gastroenterologia
city: Nagakute
country: Japan
facility: Aichi Medical University Hospital
state: Aichi
city: Sakura
country: Japan
facility: Toho University Sakura Medical Center
state: Chiba
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Sendai
country: Japan
facility: National Hospital Organization Sendai Medical Center
state: Miyagi
city: Bunkyo-ku
country: Japan
facility: Tokyo Medical And Dental University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Guadalajara
country: Mexico
facility: BRCR Global Mexico
state: Jalisco
city: Merida
country: Mexico
facility: Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion
state: Yucatan
city: Ciudad de Mexico
country: Mexico
facility: Karla Adriana Espinosa Bautista
city: Queretaro
country: Mexico
facility: Smiq S. de R.L. de C.V.
city: Bialystok
country: Poland
facility: KLIMED Marek Klimkiewicz
city: Knurow
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla
city: Knurow
country: Poland
facility: MZ Badania Slowik Zymla Sp. j.
city: Sopot
country: Poland
facility: ENDOSKOPIA Sp. z o. o.
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecinskie Centrum Medyczne
city: Warszawa
country: Poland
facility: WIP Warsaw IBD Point Profesor Kierkus
city: Warszawa
country: Poland
facility: NZOZ Vivamed Jadwiga Miecz
city: Wroclaw
country: Poland
facility: Centrum Medyczne Melita Medical
city: Bucuresti
country: Romania
facility: Medlife S.A.
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk City Clinical Hospital
state: Stavropol Region
city: Moscow
country: Russian Federation
facility: KDC "Evromedservis", OJSC
city: Novosibirsk
country: Russian Federation
facility: Limited Liability Company "Medicinsky Center SibNovoMed"
city: Novosibirsk
country: Russian Federation
facility: LLC Novosibirskiy Gastrocenter
city: Omsk
country: Russian Federation
facility: Clinic of OSMU
city: Perm
country: Russian Federation
facility: Perm Clinical Centre of the Federal Medical-Biological Agency
city: Samara
country: Russian Federation
facility: Private Healthcare Institution "Clinical Hospital" Russian Railways-Medicine "Samara city"
city: Saratov
country: Russian Federation
facility: Clinical Hospital named after S.R. Mirotvortsev
city: Smolensk
country: Russian Federation
facility: Research Institute of Antimicrobial Chemotherapy
city: Tomsk
country: Russian Federation
facility: Tomsk Regional Clinical Hospital
city: Tyumen
country: Russian Federation
facility: City Hospital JSC "Medical centre"
city: Yaroslavl
country: Russian Federation
facility: SBHI YaR "Regional Clinical Hospital"
city: Kragujevac
country: Serbia
facility: Klinicki Centar Kragujevac
city: Subotica
country: Serbia
facility: Opsta Bolnica Subotica
city: Zrenjanin
country: Serbia
facility: Opsta Bolnica "Djordje Joanovic", Odeljenje Interno, Odsek Gastroenterologija
city: Nitra
country: Slovakia
facility: KM Management spol. s.r.o.
city: Presov
country: Slovakia
facility: Gastro LM s.r.o
city: Vranov nad Toplou
country: Slovakia
facility: ENDOMED, s.r.o.
city: Bloemfontein
country: South Africa
facility: Dr van Dyk & Partners Inc
state: FREE State
city: Bloemfontein
country: South Africa
facility: IATROS International
state: FREE State
city: Bloemfontein
country: South Africa
facility: Universitas Private Hospital
state: FREE State
city: Johannesburg
country: South Africa
facility: Ahmed Kathrada Private Hospital
state: Gauteng
city: Johannesburg
country: South Africa
facility: Lenasia Clinical Trial Centre
state: Gauteng
city: Kempton Park
country: South Africa
facility: Arwyp Medical Centre
state: Gauteng
city: Kempton Park
country: South Africa
facility: Clinresco Centres (Pty) Ltd
state: Gauteng
city: Pretoria
country: South Africa
facility: Emmed Research
state: Gauteng
city: Pretoria
country: South Africa
facility: Radiology24 Jakaranda Hospital
state: Gauteng
city: Pretoria
country: South Africa
facility: Mediclinic Kloof Hospital
state: Gauteng
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
state: Madrid
city: Pathum Wan
country: Thailand
facility: King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University
state: Bangkok
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital, Prince of Songkla University
state: Songkhla
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital
city: Istanbul
country: Turkey
facility: Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi, Ic Hastaliklari Anabilim Dali
city: Mersin
country: Turkey
facility: Mersin Universitesi Tip Fakultesi Hastanesi
city: Zonguldak
country: Turkey
facility: Bulent Ecevit Universitesi Tip Fakultesi
city: Kharkiv
country: Ukraine
facility: Municipal non-profit enterprise of Kharkiv regional council "Regional clinical hospital"
city: Kharkiv
country: Ukraine
facility: Municipal non-profit enterprise "City clinical hospital #2 named after O.O.Shalimov"
city: Kyiv
country: Ukraine
facility: Medical Centre Medical Clinic Blagomed LLC
city: Kyiv
country: Ukraine
facility: Municipal Non-profit Enterprise "Kyiv City Clinical Hospital #1"
city: Kyiv
country: Ukraine
facility: Municipal Non-profit enterprise of Kyiv Regional Council "Kyiv regional hospital"
city: Kyiv
country: Ukraine
facility: Municipal non-profit enterprise of Kyiv regional council "Kyiv regional clinical hospital"
city: Vinnytsia
country: Ukraine
facility: Medical center of Limited Liability Company "Health Clinic", medical clinical research center
city: Zaporizhzhia
country: Ukraine
facility: Medical Centre "DIACENTER" LLC
city: Sutton Coldfield
country: United Kingdom
facility: Endoscopy Facility - Spire Little Aston Hospital
state: Birmingham
city: Northwood
country: United Kingdom
facility: MeDiNova North London Quality Research Site
state: Middlesex
city: Corby
country: United Kingdom
facility: MeDiNova Northamptonshire Quality Research Site
city: High Wycombe
country: United Kingdom
facility: Egin Research Ltd
city: Northwood
country: United Kingdom
facility: Chest X-ray Facility - BMI Bishops Wood Hospital
city: Nottingham
country: United Kingdom
facility: Spire Nottingham Hospital
city: Orpington
country: United Kingdom
facility: Endoscopy Facility - Orpington Endoscopy Centre
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: