Study To Evaluate The Efficacy And Safety Of Oral PF-0665... | NCT03395184 | Trialant
NCT03395184
Sponsor
Pfizer
Status
Completed
Last Update Posted
Oct 30, 2024Actual
Enrollment
244Actual
Phase
Phase 2
Conditions
Crohn's Disease
Interventions
PF-06651600 Placebo
PF-06651600
Placebo PF-06700841
PF-06700841
Countries
United States
Australia
Austria
Belgium
Bosnia and Herzegovina
Canada
Croatia
Czechia
Georgia
Germany
Hungary
Italy
Lebanon
Poland
Russia
Saudi Arabia
Serbia
Slovakia
South Africa
South Korea
Spain
Switzerland
Tunisia
Turkey (Türkiye)
Ukraine
United Arab Emirates
Protocol Section
Identification Module
NCT ID
NCT03395184
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
B7981007
Secondary IDs
ID
Type
Description
Link
2017-003359-43
EudraCT Number
PIZZICATO
Other Identifier
Alias Study Number
Brief Title
Study To Evaluate The Efficacy And Safety Of Oral PF-06651600 And PF-06700841 In Subjects With Moderate To Severe Crohn's Disease
Official Title
A PHASE 2A, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ORAL PF-06651600 AND PF-06700841 AS INDUCTION AND OPEN LABEL EXTENSION TREATMENT IN SUBJECTS WITH MODERATE TO SEVERE CROHN'S DISEASE
Acronym
Not provided
Organization
PfizerINDUSTRY
Status Module
Record Verification Date
Oct 2024
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 2, 2018Actual
Primary Completion Date
Oct 19, 2023Actual
Completion Date
Oct 19, 2023Actual
First Submitted Date
Dec 5, 2017
First Submission Date that Met QC Criteria
Jan 3, 2018
First Posted Date
Jan 10, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Oct 7, 2024
Results First Submitted that Met QC Criteria
Oct 7, 2024
Results First Posted Date
Oct 30, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 7, 2024
Last Update Posted Date
Oct 30, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
PfizerINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The objectives of this study are to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06651600 (200 mg for 8 weeks followed by 50 mg for 4 weeks) dosed once daily and PF-06700841 (60 mg for 12 weeks) dosed once daily during an induction period of 12 weeks, followed by an open label extension period at doses of 50 mg and 30 mg of PF 06651600 and PF 06700841, respectively, for 52 weeks.
Detailed Description
Not provided
Conditions Module
Conditions
Crohn's Disease
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
244Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
PF-06700841 or placebo
Experimental
Drug: Placebo PF-06700841
Drug: PF-06700841
PF-06651600 or placebo
Experimental
Drug: PF-06651600 Placebo
Drug: PF-06651600
Interventions
Name
Type
Description
Arm Group Labels
Other Names
PF-06651600 Placebo
Drug
12 weeks, followed by PF-06651600, 50 mg once daily (QD) for 52 weeks
PF-06651600 or placebo
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of Participants Achieving Greater Than or Equal to (>=) 50 Percent (%) Reduction in Simple Endoscopic Score for Crohn's Disease (SES CD50) at Week 12: Induction Period
SES CD50 was defined as 50% improvement from baseline in SES-CD. Baseline was defined as last measurement prior to first dosing on Day 1. Following bowel segments were used for calculating SES-CD scores: Ileum, right colon(C), transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 centimeter[cm]), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
Week 12
Number of Participants With Laboratory Test Abnormalities During OLE Period
Pre-specified criteria for lab abnormalities included- hematology: hemoglobin(Hb), erythrocytes (ery),hematocrit:<0.8*lower limit of normal(LLN);reticulocytes: <0.5*LLN, >1.5*upper limit of normal(ULN); ery mean corpuscular(EMC) volume: <0.9*ULN, >1.11*ULN;EMC Hb: <0.9*LLN; platelets:>1.75*ULN; leukocytes(10^9/L): <0.6*LLN,>1.5*ULN;lymphocyte,neutrophil(10^9/L):<0.8*LLN,>1.2*ULN;basophil,eosinophil,monocyte(10^9/L):>1.2*ULN;activated partial thromboplastin time (sec): >1.1*ULN. Chemistry: bilirubin(mg/dL),aspartate aminotransferase(AT),alanine AT(units per litre)>3.0*ULN; protein, albumin(g/dL):<0.8*LLN; creatinine, triglycerides (mg/dL):>1.3*ULN; urate(mg/dL):>1.2*ULN, potassium (mEq/L):<0.9*LLN; calcium (mg/dL): <0.9*LLN,>1.1*ULN. Urinalysis: pH>8;urine,glucose,protein(mg/dl); ketones, nitrite, urine Hb(scalar):>=1. Number of participants with any lab abnormality meeting pre-specified criteria are reported.
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants According to Categorization of Vital Signs During OLE Period
Secondary Outcomes
Measure
Description
Time Frame
Number of Participants With Laboratory Test Abnormalities During Induction Period
Pre-specified criteria for lab abnormalities included- hematology: hemoglobin, erythrocytes, hematocrit:<0.8*LLN; reticulocytes: <0.5*LLN, >1.5*ULN; EMC volume: <0.9*ULN, >1.11*ULN;EMC Hb: <0.9*LLN; platelets:>1.75*ULN; leukocytes(10^9/L): <0.6*LLN, >1.5*ULN; lymphocyte, neutrophil(10^9/L):<0.8*LLN, >1.2*ULN; basophil, eosinophil, monocyte(10^9/L):>1.2*ULN; activated partial thromboplastin time (sec): >1.1*ULN. Chemistry: bilirubin(mg/dL),aspartate aminotransferase(AT),alanine AT(units per litre)>3.0*ULN; protein, albumin(g/dL):<0.8*LLN; creatinine, triglycerides (mg/dL):>1.3*ULN; urate(mg/dL):>1.2*ULN, potassium (mEq/L):<0.9*LLN; calcium (mg/dL): <0.9*LLN,>1.1*ULN. Urinalysis: pH>8; urine, glucose, protein(mg/dl); ketones, nitrite, urine Hb(scalar):>=1. Number of participants with any lab abnormality meeting pre-specified criteria are reported.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male and/or female subjects 18 years to 75 years of age
Documented diagnosis of ileal, ileocolonic, or colonic CD with a minimum disease duration of 3 months, as determined by endoscopic and histopathology assessment.
Endoscopic confirmation of active disease with total SES CD total score of at least 7. For isolated ileal disease, SES CD total score should be at least 4.
An average daily liquid/soft stool frequency (SF) greater than or equal to 2.5 or daily abdominal pain (AP) greater than or equal to 2.0.
Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for CD:
•Steroids; Immunosuppressants (azathioprine [AZA], 6 MP, or methotrexate [MTX]); Anti TNF inhibitors (infliximab, adalimumab,certolizumab); Anti integrin inhibitors (eg, vedolizumab); Anti IL 12/23 inhibitor (ustekinumab).
Subjects currently receiving the following treatment for CD are eligible providing they have been on stable doses as described below:
Oral corticosteroids (prednisone or equivalent up to 25 mg/day; budesonide up to 9 mg/day). Stable dose for at least 2 weeks prior to baseline. If oral corticosteroids have been recently discontinued, they must have been stopped at least 2 weeks prior to baseline. Decreases in steroid use due to AEs are allowed.
Oral 5 ASA or sulfasalazine are allowed providing that the dose is stable for at least 4 weeks prior to baseline.
Crohn's disease related antibiotics are allowed providing that the dose is stable for at least 4 weeks prior to baseline. If antibiotics are stopped prior to baseline, they must be discontinued at least 4 days prior to baseline.
Exclusion Criteria:
Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, diverticular disease, ulcerative colitis (UC), or clinical findings suggestive of UC.
Presence of active (draining) fistulae or intra abdominal or perineal abscesses.
Strictures with obstructive symptoms.
Short bowel syndrome.
History of bowel perforation requiring surgical intervention within the past 12 months.
Previous bowel surgery resulting in an existing stoma. Subjects who have a j pouch are excluded, as a j pouch can result in a stoma.
History of bowel surgery within 6 months prior to baseline.
Subjects displaying clinical signs of fulminant colitis or toxic megacolon.
Subjects with primary sclerosing cholangitis.
Subjects with evidence of colonic adenomas, dysplasia or neoplasia.
Abnormal findings on the chest x ray film such as presence of tuberculosis (TB), general infections, heart failure, or malignancy.
Any history of either untreated or inadequately treated latent or active TB infection, current treatment for active or latent TB infection or evidence of currently active TB by chest x ray, residing with or frequent close contact with individual(s) with active TB.
Subjects receiving the following therapies within the time period described below or expected to receive any of these therapies during the study period:
>9 mg/day of oral budesonide or >25 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 2 weeks prior to baseline.
IV, IM (parenteral), or topical (rectal) treatment of 5 ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline.
Azathioprine, 6 mercaptopurine, or methotrexate within 2 weeks prior to baseline.
Anti TNF inhibitors (or biosimilars thereof) as described below:
Infliximab within 8 weeks prior to baseline;
Adalimumab within 8 weeks prior to baseline;
Certolizumab within 8 weeks prior to baseline;
Anti integrin inhibitors (eg, vedolizumab) within 8 weeks prior to baseline.
Ustekinumab within 8 weeks prior to baseline.
Interferon therapy within 8 weeks prior to baseline.
Subjects with prior treatment with lymphocyte depleting agents/therapies within 1 year prior to baseline (eg, CamPath[alemtuzumab], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc).
Subjects who have received rituximab or other selective B lymphocyte depleting agents within 1 year prior to baseline.
Subjects previously receiving leukocyte apheresis, including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline.
Other marketed immunosuppressants or biologics with immunomodulatory properties within 3 months prior to baseline.
Subjects who have received other JAK inhibitors within 3 months prior to baseline.
Subjects who have not responded to or have been intolerant of other JAK inhibitors.
Other investigational procedures(s) or product(s), such as immunosuppressants used in transplantation (eg, mycophenolate mofetil, cyclosporine, rapamycin, or tacrolimus) or live (attenuated) vaccine within 30 days prior to baseline.
14) Subjects with history of thrombotic event(s), including deep venous thrombosis (DVT), and known inherited conditions that predispose to hypercoagulability.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
75 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Pfizer CT.gov Call Center
Pfizer
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Dothan Surgery Center
Dothan
Alabama
36301
United States
Gut P.C., dba Digestive Health Specialists of the Southeast
Vermeire S, Allegretti JR, Kim HJ, Long MD, Leszczyszyn J, Schreiber S, Kierkus J, Chandler PD, Ramakrishna J, Peeva E, Vincent MS, Shojaee N, Mahling P, Banfield C, Banerjee A, Gale JD, Hung KE. Once-daily oral ritlecitinib or brepocitinib versus placebo in patients with moderate-to-severely active Crohn's disease (PIZZICATO): an international, randomised, phase 2a trial. EClinicalMedicine. 2026 Mar 10;93:103820. doi: 10.1016/j.eclinm.2026.103820. eCollection 2026 Mar.
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
A total of 645 participants were screened across 26 countries of which 401 were screen failures and 244 participants were randomized in the study.
Recruitment Details
The study consisted of a 12-weeks induction period and a 52-weeks open label extension (OLE) period. The participants who completed induction period, entered the 52-week OLE period.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) once daily (QD) orally for 12 weeks in induction period.
200 mg QD for 8 weeks, followed by 50 mg QD up to 56 weeks
PF-06651600 or placebo
Placebo PF-06700841
Drug
12 weeks, followed by PF-06700841, 30 mg QD for 52 weeks
PF-06700841 or placebo
PF-06700841
Drug
60 mg QD for 12 weeks followed by 30 mg QD for up to 52 weeks
PF-06700841 or placebo
Vital signs including blood pressure (diastolic blood pressure [DBP], systolic blood pressure [SBP], and pulse rate [PR]) were measured in a supine position using automated devices. DBP included value < 50 (millimeter of mercury [mmHg]), change >=20 (mmHg) increase and change >=20 (mmHg) decrease; SBP: value < 90 (mmHg), change >= 30 (mmHg) increase and change >= 30 (mmHg) decrease; PR: value > 120 (beats per minute [bpm]).
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During OLE Period
Single twelve lead ECGs were obtained using an automated ECG machine after participant had rested quietly for at least 10 minutes in a supine position. QTc prolongations were defined as a QTc >=480 milli second (msec) or an absolute change in QTc greater than (>) 60 msec. Clinically significant ECG findings were determined by the investigator.
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During OLE Period
An adverse event (AE) was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. An AE was considered TEAE to a given treatment if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During OLE Period
A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) or resulted in congenital anomaly/birth defect or was considered an important medical event. An SAE was considered as TESAE if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants With Discontinuations Due to Adverse Events During OLE Period
An AE was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. Discontinuations from study due to TEAEs were defined as participants with an AE record indicating the AE caused permanent discontinuation from the study but action taken with study treatment was not drug withdrawn. Permanent discontinuations from any study intervention due to TEAEs were defined as participants with an AE record indicating that action taken with study treatment was drug withdrawn. In this outcome measure number of participants with discontinuation from study due to AEs and permanent discontinuation from study intervention due to AEs are reported.
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
From start of study intervention on Day 1 up to Week 12
Number of Participants According to Categorization of Vital Signs During Induction Period
Vital signs including blood pressure (diastolic blood pressure [DBP], systolic blood pressure [SBP], and pulse rate [PR]) were measured in a supine position using automated devices. DBP included value < 50 (mmHg), change >=20 (mmHg) increase and change >=20 (mmHg) decrease; SBP: value < 90 (mmHg), change >= 30 (mmHg) increase and PR: value > 120 (bpm).
From start of study intervention on Day 1 up to Week 12
Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During Induction Period
Single twelve lead ECGs were obtained using an automated ECG machine after participant had rested quietly for at least 10 minutes in a supine position. QTc prolongations were defined as a QTc greater than or equal to (>=)480 milli second (msec) or an absolute change in QTc greater than (>)60 msec. Clinically significant ECG findings were determined by the investigator.
From start of study intervention on Day 1 up to Week 12
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During Induction Period
An AE was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. An AE was considered TEAE to a given treatment if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.
From start of study intervention on Day 1 up to Week 12
Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During Induction Period
A SAE was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) or resulted in congenital anomaly/birth defect or was considered an important medical event. An SAE was considered as TESAE if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.
From start of study intervention on Day 1 up to Week 12
Number of Participants Discontinuation Due to Adverse Events During Induction Period
An AE was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. Discontinuations from study due to TEAEs were defined as participants with an AE record indicating the AE caused permanent discontinuation from the study but action taken with study treatment was not drug withdrawn. Permanent discontinuations from any study intervention due to TEAEs were defined as participants with an AE record indicating that action taken with study treatment was drug withdrawn. In this outcome measure number of participants with discontinuation from study due to AEs and permanent discontinuation from study intervention due to AEs are reported.
From start of study intervention on Day 1 up to Week 12
Number of Participants With Serious Infections During Induction Period
Participants were monitored for development of any infection (viral, bacterial and fungal). Serious infections were treated infections that required parenteral antimicrobial therapy and were present with positive pre-treatment culture and required hospitalization for treatment/met other criteria that required the infection to be classified as SAE. An SAE was any untoward medical occurrence at any dose that: resulted in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity/results in congenital anomaly/birth defect. Treated infections were infections that required antimicrobial therapy by any route of administration/required any surgical intervention (e.g., incision and drainage).
From start of study intervention on Day 1 up to Week 12
Percentage of Participants Who Achieved Clinically Meaningful Endoscopic Improvement (CMEI) (Reduction of >=3 Points From Baseline in SES-CD Score) at Week 12: Induction Period
CMEI was defined as reduction of >=3 points from baseline in SES-CD score as assessed by centrally read SES-CD score. Baseline: last measurement prior to first dosing on Day1. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for 4 domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on scale of 0-3, higher scores indicated more severe condition. Presence of ulcers score: 0=none,1=small ulcer: (0.1-0.5cm),2=Large ulcer(0.5-2cm),3=very large ulcer(>2cm); ulcerated surface score: 0=none,1=<10%,2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
Week 12
Mean Change From Baseline in SES-CD Score at Week 12: Induction Period
Mean change from baseline in SES-CD score at Week 12 analyzed using analysis of covariance(ANCOVA)model with treatment,baseline disease activity/extent as factors, baseline SES CD score as covariate. Baseline=last measurement prior to first dosing on Day 1. Following bowel segments used for calculating SES-CD scores: Ileum,right C,transverse C,left C,rectum. Each segment assessed for four domains:presence of ulcers, ulcerated surface, affected surface,presence of narrowing, each score on a scale of 0-3,higher scores=more severe condition. Presence of ulcers score:0=none,1=small ulcer:(0.1-0.5cm),2=large ulcer(0.5-2cm),3=very large ulcer(>2 cm);ulcerated surface score:0=none,1=<10%,2=10-30%,3=>30%;affected surface score:0=unaffected segment,1=<50%, 2=50-75%,3=>75%;presence of narrowing score:0=none,1=single,can be passed,2=multiple can be passed,3=cannot be passed. Total SES CD score=sum of each domain score for all 5 bowel segments,range from 0 to 60,higher score =more severe disease.
Baseline and Week 12
Percentage of Participants Achieving >=25% Reduction in SES-CD From Baseline (SES-CD 25) at Week 12: Induction Period
SES CD25 was defined as >=25% improvement from baseline in SES CD. Baseline was defined as the last measurement prior to first dosing on Day 1. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 centimeter[cm]), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
Week 12
Percentage of Participants Achieving Endoscopic Remission (SES-CD Score of <= 2) at Week 12: Induction Period
Endoscopic remission was defined as SES-CD score of <= 2. Following bowel segments were used for calculating SES-CD scores: Ileum, right colon(C), transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 centimeter[cm]), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
Week 12
Percentage of Participants Achieving Mucosal Healing at Week 12: Induction Period
Mucosal healing was defined as complete absence of ulcers.
Week 12
Percentage of Participants Achieving CMEI at Week 64 Among Participants Who Achieved CMEI Response at Week 12 (Baseline of OLE Period): OLE Period
CMEI was defined as reduction of >=3 points from baseline as assessed by centrally read SES CD score. Baseline: last measurement prior to first dosing on Day 1 of Week 12. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on scale of 0-3, higher scores indicated more severe condition. Presence of ulcers score: 0=none,1=small ulcer: (0.1-0.5 cm),2=Large ulcer(0.5-2 cm),3=very large ulcer(>2 cm); ulcerated surface score: 0=none,1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0-60, higher score indicating more severe disease.
Week 64 (Week 52 of OLE period)
Percentage of Participants Achieving SES CD 25 and SES CD 50 at Week 64 Among Participants Who Achieved SES CD 25 and SES CD 50 at Week 12 (Baseline of OLE Period): OLE Period
SES CD50 and SES CD25: 50% and 25% improvement from baseline, respectively. Baseline: last measurement prior to first dosing on Day 1 of Week 12. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 cm), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
Week 64 (Week 52 of OLE period)
Dothan
Alabama
36305
United States
Brighton Surgical Center
Beverly Hills
California
90210
United States
Entertainment Medical Group
Los Angeles
California
90036
United States
Gastrointestinal Biosciences Clinical Trials, LLC
Los Angeles
California
90067
United States
Stanford Medicine Outpatient Center - Digestive Health Center
Redwood City
California
94063
United States
Front Range Endoscopy Center
Colorado Springs
Colorado
80903
United States
Peak Gastroenterology Associates
Colorado Springs
Colorado
80907
United States
Gastro Florida
Clearwater
Florida
33756-3839
United States
Gastro Florida
Clearwater
Florida
33756
United States
West Coast Endoscopy Center
Clearwater
Florida
33756
United States
Gastro Florida
Clearwater
Florida
33762
United States
UF Health Jacksonville - Gastroenterology Emerson
Jacksonville
Florida
32207
United States
Millenia Surgery Center
Orlando
Florida
32811
United States
HMD Research LLC
Orlando
Florida
32819
United States
Treasure Valley Medical Research
Boise
Idaho
83706
United States
WestGlen Gastrointestinal Consultants, P.A.
Shawnee Mission
Kansas
66217
United States
Chevy Chase Endoscopy Center
Chevy Chase
Maryland
20815
United States
MGG Group Co., Inc., Chevy Chase Clinical Research
Chevy Chase
Maryland
20815
United States
Capitol Research
Rockville
Maryland
20850
United States
Brigham and Women's Hospital
Boston
Massachusetts
02115
United States
Mass Eye and Ear, Longwood
Boston
Massachusetts
02115
United States
Brigham and Women's Hospital
Chestnut Hill
Massachusetts
02467
United States
Clinical Research Institute of Michigan, LLC
Chesterfield
Michigan
48047
United States
Eastside Endoscopy Center
Macomb
Michigan
48044
United States
Weill Cornell Medical College - New York Presbyterian Hospital
New York
New York
10021
United States
Weill Cornell Medical College
New York
New York
10021
United States
New York Presbyterian Hospital - Weill Cornell Medical College (Colonoscopy)
New York
New York
10065
United States
New York Presbyterian Hospital - Weill Cornell Medical College Investigational Pharmacy
New York
New York
10065
United States
Weill Cornell Medical College - New York Presbyterian Hospital (Endoscopy Suite)
New York
New York
10065
United States
Weill Cornell Medical College - New York Presbyterian Hospital
New York
New York
10065
United States
DiGiovanna Institute for Medical Education And Research
Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gopalsamy A, Hayward MM, Hegen M, Hollingshead BD, Jussif J, Knafels JD, Limburg DC, Lin D, Lin TH, Pierce BS, Saiah E, Sharma R, Symanowicz PT, Telliez JB, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X, Zhang L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018 Oct 11;61(19):8597-8612. doi: 10.1021/acs.jmedchem.8b00917. Epub 2018 Aug 16.
Participants received PF-06651600 (ritlecitinib) 200 milligrams (mg) QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
FG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
FG003
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
FG005
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.
Participants who received brepocitinib 60 mg QD in the induction period were administered brepocitinib 30 mg QD for 52 weeks in OLE period.
FG00079 subjects
FG00193 subjects
FG00272 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
COMPLETED
FG00068 subjects
FG00184 subjects
FG00265 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
NOT COMPLETED
FG00011 subjects
FG0019 subjects
FG0027 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Type
Comment
Reasons
Adverse Event
FG0006 subjects
FG0014 subjects
FG0024 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
No longer meets eligibility criteria
FG0000 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0002 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Lack of Efficacy
FG0002 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG004
Other
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
OLE Period (Up to 52 Weeks)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00336 subjectsParticipants who received treatment in OLE period.
FG00484 subjectsParticipants who received treatment in OLE period.
FG00532 subjectsParticipants who received treatment in OLE period.
FG00664 subjectsParticipants who received treatment in OLE period.
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00320 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00316 subjects
FG004
Type
Comment
Reasons
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
The full analysis set (FAS) included all randomized participants who received at least one dose of the randomized investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
BG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
BG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00079
BG00193
BG00272
BG003244
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00036.1± 13.03
BG00134.6± 10.64
BG00236.5± 12.70
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00037
BG00141
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0002
BG0011
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Percentage of Participants Achieving Greater Than or Equal to (>=) 50 Percent (%) Reduction in Simple Endoscopic Score for Crohn's Disease (SES CD50) at Week 12: Induction Period
SES CD50 was defined as 50% improvement from baseline in SES-CD. Baseline was defined as last measurement prior to first dosing on Day 1. Following bowel segments were used for calculating SES-CD scores: Ileum, right colon(C), transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 centimeter[cm]), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
FAS included all randomized participants who received at least one dose of the randomized investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group. Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Number
90% Confidence Interval
Percentage of participants
Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00078
OG00192
OG00271
Title
Denominators
Categories
Title
Measurements
OG00012.8(7.1 to 19.9)
OG00127.2(19.6 to 35.7)
OG00233.8(25.1 to 43.1)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Min risk weight method(Mehrotra-Railkar)
0.0119
Percentage risk difference
14.3
2-Sided
90
4.0
24.5
90% CI was calculated using minimum (min) risk weight method (Mehrotra-Railkar 2000)
Other
OG000
OG002
Min risk weight method(Mehrotra-Railkar)
Primary
Number of Participants With Laboratory Test Abnormalities During OLE Period
Pre-specified criteria for lab abnormalities included- hematology: hemoglobin(Hb), erythrocytes (ery),hematocrit:<0.8*lower limit of normal(LLN);reticulocytes: <0.5*LLN, >1.5*upper limit of normal(ULN); ery mean corpuscular(EMC) volume: <0.9*ULN, >1.11*ULN;EMC Hb: <0.9*LLN; platelets:>1.75*ULN; leukocytes(10^9/L): <0.6*LLN,>1.5*ULN;lymphocyte,neutrophil(10^9/L):<0.8*LLN,>1.2*ULN;basophil,eosinophil,monocyte(10^9/L):>1.2*ULN;activated partial thromboplastin time (sec): >1.1*ULN. Chemistry: bilirubin(mg/dL),aspartate aminotransferase(AT),alanine AT(units per litre)>3.0*ULN; protein, albumin(g/dL):<0.8*LLN; creatinine, triglycerides (mg/dL):>1.3*ULN; urate(mg/dL):>1.2*ULN, potassium (mEq/L):<0.9*LLN; calcium (mg/dL): <0.9*LLN,>1.1*ULN. Urinalysis: pH>8;urine,glucose,protein(mg/dl); ketones, nitrite, urine Hb(scalar):>=1. Number of participants with any lab abnormality meeting pre-specified criteria are reported.
Safety analysis set (SAS) included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Count of Participants
Participants
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
ID
Title
Description
OG000
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Primary
Number of Participants According to Categorization of Vital Signs During OLE Period
Vital signs including blood pressure (diastolic blood pressure [DBP], systolic blood pressure [SBP], and pulse rate [PR]) were measured in a supine position using automated devices. DBP included value < 50 (millimeter of mercury [mmHg]), change >=20 (mmHg) increase and change >=20 (mmHg) decrease; SBP: value < 90 (mmHg), change >= 30 (mmHg) increase and change >= 30 (mmHg) decrease; PR: value > 120 (beats per minute [bpm]).
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Count of Participants
Participants
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
ID
Title
Description
OG000
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
Primary
Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During OLE Period
Single twelve lead ECGs were obtained using an automated ECG machine after participant had rested quietly for at least 10 minutes in a supine position. QTc prolongations were defined as a QTc >=480 milli second (msec) or an absolute change in QTc greater than (>) 60 msec. Clinically significant ECG findings were determined by the investigator.
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Count of Participants
Participants
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
ID
Title
Description
OG000
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
OG002
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During OLE Period
An adverse event (AE) was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. An AE was considered TEAE to a given treatment if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo).
Posted
Count of Participants
Participants
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
ID
Title
Description
OG000
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
OG002
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Primary
Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During OLE Period
A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) or resulted in congenital anomaly/birth defect or was considered an important medical event. An SAE was considered as TESAE if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo).
Posted
Count of Participants
Participants
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
ID
Title
Description
OG000
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
Primary
Number of Participants With Discontinuations Due to Adverse Events During OLE Period
An AE was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. Discontinuations from study due to TEAEs were defined as participants with an AE record indicating the AE caused permanent discontinuation from the study but action taken with study treatment was not drug withdrawn. Permanent discontinuations from any study intervention due to TEAEs were defined as participants with an AE record indicating that action taken with study treatment was drug withdrawn. In this outcome measure number of participants with discontinuation from study due to AEs and permanent discontinuation from study intervention due to AEs are reported.
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo).
Posted
Count of Participants
Participants
From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
ID
Title
Description
OG000
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
Secondary
Number of Participants With Laboratory Test Abnormalities During Induction Period
Pre-specified criteria for lab abnormalities included- hematology: hemoglobin, erythrocytes, hematocrit:<0.8*LLN; reticulocytes: <0.5*LLN, >1.5*ULN; EMC volume: <0.9*ULN, >1.11*ULN;EMC Hb: <0.9*LLN; platelets:>1.75*ULN; leukocytes(10^9/L): <0.6*LLN, >1.5*ULN; lymphocyte, neutrophil(10^9/L):<0.8*LLN, >1.2*ULN; basophil, eosinophil, monocyte(10^9/L):>1.2*ULN; activated partial thromboplastin time (sec): >1.1*ULN. Chemistry: bilirubin(mg/dL),aspartate aminotransferase(AT),alanine AT(units per litre)>3.0*ULN; protein, albumin(g/dL):<0.8*LLN; creatinine, triglycerides (mg/dL):>1.3*ULN; urate(mg/dL):>1.2*ULN, potassium (mEq/L):<0.9*LLN; calcium (mg/dL): <0.9*LLN,>1.1*ULN. Urinalysis: pH>8; urine, glucose, protein(mg/dl); ketones, nitrite, urine Hb(scalar):>=1. Number of participants with any lab abnormality meeting pre-specified criteria are reported.
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group. Here "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.
Posted
Count of Participants
Participants
From start of study intervention on Day 1 up to Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
Secondary
Number of Participants According to Categorization of Vital Signs During Induction Period
Vital signs including blood pressure (diastolic blood pressure [DBP], systolic blood pressure [SBP], and pulse rate [PR]) were measured in a supine position using automated devices. DBP included value < 50 (mmHg), change >=20 (mmHg) increase and change >=20 (mmHg) decrease; SBP: value < 90 (mmHg), change >= 30 (mmHg) increase and PR: value > 120 (bpm).
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group. Here, 'Number Analyzed' signifies number of participants evaluable for specific rows.
Posted
Count of Participants
Participants
From start of study intervention on Day 1 up to Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Secondary
Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During Induction Period
Single twelve lead ECGs were obtained using an automated ECG machine after participant had rested quietly for at least 10 minutes in a supine position. QTc prolongations were defined as a QTc greater than or equal to (>=)480 milli second (msec) or an absolute change in QTc greater than (>)60 msec. Clinically significant ECG findings were determined by the investigator.
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group. Here "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.
Posted
Count of Participants
Participants
From start of study intervention on Day 1 up to Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During Induction Period
An AE was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. An AE was considered TEAE to a given treatment if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group.
Posted
Count of Participants
Participants
From start of study intervention on Day 1 up to Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Secondary
Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During Induction Period
A SAE was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) or resulted in congenital anomaly/birth defect or was considered an important medical event. An SAE was considered as TESAE if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group.
Posted
Count of Participants
Participants
From start of study intervention on Day 1 up to Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
Secondary
Number of Participants Discontinuation Due to Adverse Events During Induction Period
An AE was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. Discontinuations from study due to TEAEs were defined as participants with an AE record indicating the AE caused permanent discontinuation from the study but action taken with study treatment was not drug withdrawn. Permanent discontinuations from any study intervention due to TEAEs were defined as participants with an AE record indicating that action taken with study treatment was drug withdrawn. In this outcome measure number of participants with discontinuation from study due to AEs and permanent discontinuation from study intervention due to AEs are reported.
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group.
Posted
Count of Participants
Participants
From start of study intervention on Day 1 up to Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
Secondary
Number of Participants With Serious Infections During Induction Period
Participants were monitored for development of any infection (viral, bacterial and fungal). Serious infections were treated infections that required parenteral antimicrobial therapy and were present with positive pre-treatment culture and required hospitalization for treatment/met other criteria that required the infection to be classified as SAE. An SAE was any untoward medical occurrence at any dose that: resulted in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity/results in congenital anomaly/birth defect. Treated infections were infections that required antimicrobial therapy by any route of administration/required any surgical intervention (e.g., incision and drainage).
SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group.
Posted
Count of Participants
Participants
From start of study intervention on Day 1 up to Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Secondary
Percentage of Participants Who Achieved Clinically Meaningful Endoscopic Improvement (CMEI) (Reduction of >=3 Points From Baseline in SES-CD Score) at Week 12: Induction Period
CMEI was defined as reduction of >=3 points from baseline in SES-CD score as assessed by centrally read SES-CD score. Baseline: last measurement prior to first dosing on Day1. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for 4 domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on scale of 0-3, higher scores indicated more severe condition. Presence of ulcers score: 0=none,1=small ulcer: (0.1-0.5cm),2=Large ulcer(0.5-2cm),3=very large ulcer(>2cm); ulcerated surface score: 0=none,1=<10%,2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
FAS included all randomized participants who received at least one dose of the randomized investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group. Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Number
90% Confidence Interval
Percentage of participants
Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
Secondary
Mean Change From Baseline in SES-CD Score at Week 12: Induction Period
Mean change from baseline in SES-CD score at Week 12 analyzed using analysis of covariance(ANCOVA)model with treatment,baseline disease activity/extent as factors, baseline SES CD score as covariate. Baseline=last measurement prior to first dosing on Day 1. Following bowel segments used for calculating SES-CD scores: Ileum,right C,transverse C,left C,rectum. Each segment assessed for four domains:presence of ulcers, ulcerated surface, affected surface,presence of narrowing, each score on a scale of 0-3,higher scores=more severe condition. Presence of ulcers score:0=none,1=small ulcer:(0.1-0.5cm),2=large ulcer(0.5-2cm),3=very large ulcer(>2 cm);ulcerated surface score:0=none,1=<10%,2=10-30%,3=>30%;affected surface score:0=unaffected segment,1=<50%, 2=50-75%,3=>75%;presence of narrowing score:0=none,1=single,can be passed,2=multiple can be passed,3=cannot be passed. Total SES CD score=sum of each domain score for all 5 bowel segments,range from 0 to 60,higher score =more severe disease.
FAS included all randomized participants who received at least one dose of the randomized investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group. Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Least Squares Mean
90% Confidence Interval
Units on a scale
Baseline and Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
Secondary
Percentage of Participants Achieving >=25% Reduction in SES-CD From Baseline (SES-CD 25) at Week 12: Induction Period
SES CD25 was defined as >=25% improvement from baseline in SES CD. Baseline was defined as the last measurement prior to first dosing on Day 1. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 centimeter[cm]), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
FAS included all randomized participants who received at least one dose of the randomized investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group. Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Number
90% Confidence Interval
Percentage of participants
Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
Secondary
Percentage of Participants Achieving Endoscopic Remission (SES-CD Score of <= 2) at Week 12: Induction Period
Endoscopic remission was defined as SES-CD score of <= 2. Following bowel segments were used for calculating SES-CD scores: Ileum, right colon(C), transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 centimeter[cm]), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
FAS included all randomized participants who received at least one dose of the randomized investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group. Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Number
90% Confidence Interval
Percentage of participants
Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
Secondary
Percentage of Participants Achieving Mucosal Healing at Week 12: Induction Period
Mucosal healing was defined as complete absence of ulcers.
FAS included all randomized participants who received at least one dose of the randomized investigational drug (ritlecitinib, brepocitinib, or placebo). Participants who received placebo in induction period were analyzed as a single reporting group. Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Number
90% Confidence Interval
Percentage of participants
Week 12
ID
Title
Description
OG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Secondary
Percentage of Participants Achieving CMEI at Week 64 Among Participants Who Achieved CMEI Response at Week 12 (Baseline of OLE Period): OLE Period
CMEI was defined as reduction of >=3 points from baseline as assessed by centrally read SES CD score. Baseline: last measurement prior to first dosing on Day 1 of Week 12. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on scale of 0-3, higher scores indicated more severe condition. Presence of ulcers score: 0=none,1=small ulcer: (0.1-0.5 cm),2=Large ulcer(0.5-2 cm),3=very large ulcer(>2 cm); ulcerated surface score: 0=none,1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0-60, higher score indicating more severe disease.
FAS included all randomized participants who received at least one dose of the randomized investigational drug (ritlecitinib, brepocitinib, or placebo). Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Posted
Number
90% Confidence Interval
Percentage of participants
Week 64 (Week 52 of OLE period)
ID
Title
Description
OG000
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Secondary
Percentage of Participants Achieving SES CD 25 and SES CD 50 at Week 64 Among Participants Who Achieved SES CD 25 and SES CD 50 at Week 12 (Baseline of OLE Period): OLE Period
SES CD50 and SES CD25: 50% and 25% improvement from baseline, respectively. Baseline: last measurement prior to first dosing on Day 1 of Week 12. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 cm), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.
FAS included all randomized participants who received at least one dose of the randomized investigational drug (ritlecitinib, brepocitinib, or placebo). Here "Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed"=participants evaluable for specified rows.
Posted
Number
90% Confidence Interval
Percentage of participants
Week 64 (Week 52 of OLE period)
ID
Title
Description
OG000
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Time Frame
Induction Period: From start of study intervention on Day 1 up to Week 12 (for a maximum duration of 12 weeks); OLE Period: From start of study intervention in OLE period (Week 12) up to 4 weeks after last dose of study intervention on Week 64 (for a maximum duration of 56 weeks)
Description
Same event may appear as both non-SAE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and non-serious in another participants, or one participant may have experienced both serious and non-serious event during the study.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Induction Period: Placebo QD
Participants received placebo matched to either PF-06651600 (ritlecitinib) or PF-06700841 (brepocitinib) QD orally for 12 weeks in induction period.
0
79
6
79
20
79
EG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
0
93
4
93
20
93
EG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
0
72
4
72
17
72
EG003
OLE Period: Placebo QD -> Ritlecitinib 50 mg QD
Participants who received placebo matched to ritlecitinib during the induction period were administered ritlecitinib 50 mg QD orally for 52 weeks in OLE period.
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
0
84
10
84
34
84
EG005
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.
Participants who received brepocitinib 60 mg QD in the induction period were administered brepocitinib 30 mg QD for 52 weeks in OLE period.
0
64
16
64
31
64
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA v26.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG0031 affected36 at risk
EG0040 affected84 at risk
EG0050 affected32 at risk
EG0060 affected64 at risk
Lymphopenia
Blood and lymphatic system disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Crohn's disease
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0005 affected79 at risk
EG0012 affected93 at risk
EG0020 affected72 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Ileus paralytic
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Rectal ulcer
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected93 at risk
EG0020 affected72 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Subileus
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Pyrexia
General disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected93 at risk
EG0020 affected72 at risk
EG003
Abdominal abscess
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Bartholin's abscess
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Cytomegalovirus colitis
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0021 affected72 at risk
EG003
Cytomegalovirus infection
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected93 at risk
EG0021 affected72 at risk
EG003
Gastritis viral
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Kidney infection
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Mesenteric abscess
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0021 affected72 at risk
EG003
Cervix carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Parathyroid tumour benign
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Thyroid adenoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Female genital tract fistula
Reproductive system and breast disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Hypertension
Vascular disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0021 affected72 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG0033 affected36 at risk
EG0040 affected84 at risk
EG0052 affected32 at risk
EG0062 affected64 at risk
Lymphopenia
Blood and lymphatic system disorders
MedDRA v26.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0013 affected93 at risk
EG0024 affected72 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0012 affected93 at risk
EG0024 affected72 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Aphthous ulcer
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Crohn's disease
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0012 affected93 at risk
EG0022 affected72 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Fatigue
General disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Peripheral swelling
General disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Pyrexia
General disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Folliculitis
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Influenza
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0012 affected93 at risk
EG0020 affected72 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Blood creatinine increased
Investigations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
SARS-CoV-2 test positive
Investigations
MedDRA v26.1
Non-systematic Assessment
EG0003 affected79 at risk
EG0016 affected93 at risk
EG0021 affected72 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0013 affected93 at risk
EG0022 affected72 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Headache
Nervous system disorders
MedDRA v26.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0013 affected93 at risk
EG0025 affected72 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected93 at risk
EG0024 affected72 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Hypertension
Vascular disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected93 at risk
EG0020 affected72 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
OG002
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.
Participants who received brepocitinib 60 mg QD in the induction period were administered brepocitinib 30 mg QD for 52 weeks in OLE period.
Units
Counts
Participants
OG00036
OG00183
OG00232
OG00363
Title
Denominators
Categories
Title
Measurements
OG00033
OG00176
OG00226
OG00356
OG002
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.
Participants who received brepocitinib 60 mg QD in the induction period were administered brepocitinib 30 mg QD for 52 weeks in OLE period.
Units
Counts
Participants
OG00036
OG00183
OG00232
OG00363
Title
Denominators
Categories
DBP; value < 50 (mmHg)
Title
Measurements
OG0000
OG0012
OG0020
OG0031
DBP; change >=20 (mmHg) increase
Title
Measurements
OG0004
OG0016
OG0022
OG003
DBP; change >=20 (mmHg) decrease
Title
Measurements
OG0001
OG0014
OG0023
OG003
PR; value > 120 (bpm)
Title
Measurements
OG0000
OG0011
OG0020
OG003
SBP; value < 90 (mmHg)
Title
Measurements
OG0000
OG0012
OG0020
OG003
SBP; change >= 30 (mmHg) increase
Title
Measurements
OG0001
OG0012
OG0020
OG003
SBP; change >= 30 (mmHg) decrease
Title
Measurements
OG0003
OG0010
OG0023
OG003
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.
Participants who received brepocitinib 60 mg QD in the induction period were administered brepocitinib 30 mg QD for 52 weeks in OLE period.
Units
Counts
Participants
OG00023
OG00150
OG00221
OG00340
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0031
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.
Participants who received brepocitinib 60 mg QD in the induction period were administered brepocitinib 30 mg QD for 52 weeks in OLE period.
Units
Counts
Participants
OG00036
OG00184
OG00232
OG00364
Title
Denominators
Categories
Title
Measurements
OG00032
OG00158
OG00225
OG00354
OG002
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.
Participants who received brepocitinib 60 mg QD in the induction period were administered brepocitinib 30 mg QD for 52 weeks in OLE period.
Units
Counts
Participants
OG00036
OG00184
OG00232
OG00364
Title
Denominators
Categories
Title
Measurements
OG0006
OG00110
OG0025
OG00316
OG002
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.
Participants who received brepocitinib 60 mg QD in the induction period were administered brepocitinib 30 mg QD for 52 weeks in OLE period.
Units
Counts
Participants
OG00036
OG00184
OG00232
OG00364
Title
Denominators
Categories
Discontinuation from study due to TEAEs
Title
Measurements
OG0000
OG0011
OG0020
OG0030
Permanent discontinuation from any study intervention due to TEAEs
Title
Measurements
OG0007
OG00113
OG0024
OG003
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00078
OG00192
OG00272
Title
Denominators
Categories
Title
Measurements
OG00067
OG00172
OG00261
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00068
OG00183
OG00263
Title
Denominators
Categories
Title
Measurements
OG0001
OG0010
OG0020
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00079
OG00193
OG00272
Title
Denominators
Categories
Title
Measurements
OG00051
OG00146
OG00249
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00079
OG00193
OG00272
Title
Denominators
Categories
Title
Measurements
OG0006
OG0014
OG0024
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00079
OG00193
OG00272
Title
Denominators
Categories
Discontinuations from study due to TEAEs
Title
Measurements
OG0000
OG0011
OG0020
Permanent discontinuations from any study intervention due to TEAEs
Title
Measurements
OG0006
OG0014
OG0024
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00079
OG00193
OG00272
Title
Denominators
Categories
Title
Measurements
OG0000
OG0011
OG0022
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00078
OG00192
OG00271
Title
Denominators
Categories
Title
Measurements
OG00029.5(21.7 to 38.9)
OG00142.4(34.2 to 51.5)
OG00257.7(47.6 to 67.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Min risk weight method(Mehrotra-Railkar)
0.0390
Percentage risk difference
13.3
2-Sided
90
1.0
25.7
90% CI was calculated using minimum risk weight method (Mehrotra-Railkar, 2000).
Other
OG000
OG002
Min risk weight method(Mehrotra-Railkar)
0.0001
Percentage risk difference
29.7
2-Sided
90
17.2
42.2
90% CI was calculated using minimum risk weight method (Mehrotra-Railkar, 2000).
Other
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00068
OG00182
OG00263
Title
Denominators
Categories
Title
Measurements
OG000-0.1(-1.32 to 1.12)
OG001-3.1(-4.22 to -2.02)
OG002-5.0(-6.36 to -3.72)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
The ANCOVA model included treatment and baseline disease activity/extent as factors, and baseline SES-CD score as a covariate.
0.0007
LS mean difference
-3.0
2-Sided
90
-4.55
-1.48
Other
OG000
OG002
ANCOVA
The ANCOVA model included treatment and baseline disease activity/extent as factors, and baseline SES-CD score as a covariate.
<.0001
LS mean difference
-4.9
2-Sided
90
-6.62
-3.26
Other
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00078
OG00192
OG00271
Title
Denominators
Categories
Title
Measurements
OG00025.6(17.7 to 34.3)
OG00139.1(30.6 to 47.4)
OG00256.3(46.2 to 66.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Min risk weight method(Mehrotra-Railkar)
0.0279
Percentage risk difference
13.9
2-Sided
90
2.1
25.6
90% CI was calculated using using minimum risk weight method (Mehrotra-Railkar, 2000).
Other
OG000
OG002
Min risk weight method(Mehrotra-Railkar)
<.0001
Percentage risk difference
31.5
2-Sided
90
19.1
43.9
90% CI was calculated using minimum risk weight method (Mehrotra-Railkar, 2000).
Other
OG001
Induction Period: Ritlecitinib 200 mg/50 mg QD
Participants received PF-06651600 (ritlecitinib) 200 mg QD orally for 8 weeks followed by ritlecitinib 50 mg QD orally for 4 weeks in induction period.
OG002
Induction Period: Brepocitinib 60 mg QD
Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period.
Units
Counts
Participants
OG00078
OG00192
OG00271
Title
Denominators
Categories
Title
Measurements
OG0005.1(2.3 to 11.2)
OG0017.6(4.0 to 13.2)
OG00212.7(7.2 to 20.8)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Min risk weight method(Mehrotra-Railkar)
0.2922
Percentage risk difference
2.5
2-Sided
90
-4.3
9.3
90% CI was calculated using minimum risk weight method (Mehrotra-Railkar, 2000).
Other
OG000
OG002
Min risk weight method(Mehrotra-Railkar)
0.0449
Percentage risk difference
7.4
2-Sided
90
-0.4
15.2
90% CI was calculated using minimum risk weight method (Mehrotra-Railkar, 2000).
Other
Units
Counts
Participants
OG00078
OG00192
OG00271
Title
Denominators
Categories
Title
Measurements
OG0005.1(2.3 to 11.2)
OG00110.9(6.1 to 17.7)
OG00216.9(10.1 to 25.8)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Min risk weight method(Mehrotra-Railkar)
0.0998
Percentage risk difference
5.8
2-Sided
90
-1.6
13.3
90% CI was calculated using minimum risk weight method (Mehrotra-Railkar, 2000).
Other
OG000
OG002
Min risk weight method(Mehrotra-Railkar)
0.0111
Percentage risk difference
11.8
2-Sided
90
2.8
20.9
90% CI was calculated using minimum risk weight method (Mehrotra-Railkar, 2000).
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
OG002
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.
Participants who received ritlecitinib 200 mg /50 mg QD in the induction period were administered ritlecitinib 50 mg QD for 52 weeks in OLE period.
OG002
OLE Period: Placebo QD -> Brepocitinib 30 mg QD
Participants who received placebo matched to brepocitinib in the induction period were administered brepocitinib 30 mg QD orally for 52 weeks in OLE period.