Crohn's Disease
Conditions
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.
Interventions
DRUGPF-06651600 Placebo
12 weeks, followed by PF-06651600, 50 mg once daily (QD) for 52 weeks
DRUGPF-06651600
200 mg QD for 8 weeks, followed by 50 mg QD up to 56 weeks
DRUGPlacebo PF-06700841
12 weeks, followed by PF-06700841, 30 mg QD for 52 weeks
DRUGPF-06700841
60 mg QD for 12 weeks followed by 30 mg QD for up to 52 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male and/or female subjects 18 years to 75 years of age 2. Documented diagnosis of ileal, ileocolonic, or colonic CD with a minimum disease duration of 3 months, as determined by endoscopic and histopathology assessment. 3. 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. 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. 5. 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). 6. 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
1. Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, diverticular disease, ulcerative colitis (UC), or clinical findings suggestive of UC. 2. Presence of active (draining) fistulae or intra abdominal or perineal abscesses. 3. Strictures with obstructive symptoms. 4. Short bowel syndrome. 5. History of bowel perforation requiring surgical intervention within the past 12 months. 6. 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. 7. History of bowel surgery within 6 months prior to baseline. 8. Subjects displaying clinical signs of fulminant colitis or toxic megacolon. 9. Subjects with primary sclerosing cholangitis. 10. Subjects with evidence of colonic adenomas, dysplasia or neoplasia. 11. Abnormal findings on the chest x ray film such as presence of tuberculosis (TB), general infections, heart failure, or malignancy. 12. 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. 13. Subjects receiving the following therapies within the time period described below or expected to receive any of these therapies during the study period: 1. \>9 mg/day of oral budesonide or \>25 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 2 weeks prior to baseline. 2. IV, IM (parenteral), or topical (rectal) treatment of 5 ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline. 3. Azathioprine, 6 mercaptopurine, or methotrexate within 2 weeks prior to baseline. 4. 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; 5. Anti integrin inhibitors (eg, vedolizumab) within 8 weeks prior to baseline. 6. Ustekinumab within 8 weeks prior to baseline. 7. Interferon therapy within 8 weeks prior to baseline. 8. 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). 9. Subjects who have received rituximab or other selective B lymphocyte depleting agents within 1 year prior to baseline. 10. Subjects previously receiving leukocyte apheresis, including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline. 11. Other marketed immunosuppressants or biologics with immunomodulatory properties within 3 months prior to baseline. 12. Subjects who have received other JAK inhibitors within 3 months prior to baseline. 13. Subjects who have not responded to or have been intolerant of other JAK inhibitors. 14. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 12 | 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. |
| Number of Participants With Laboratory Test Abnormalities During OLE Period | From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks) | 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. |
| Number of Participants According to Categorization of Vital Signs During OLE Period | From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks) | 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 \[bpm\]). |
| Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During OLE Period | From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks) | 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) During OLE Period | From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks) | 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. |
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During OLE Period | From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks) | 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. |
| Number of Participants With Discontinuations Due to Adverse Events During OLE Period | From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 12 | 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. |
| Mean Change From Baseline in SES-CD Score at Week 12: Induction Period | Baseline and Week 12 | 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. |
| Percentage of Participants Achieving >=25% Reduction in SES-CD From Baseline (SES-CD 25) at Week 12: Induction Period | Week 12 | 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. |
| Number of Participants With Laboratory Test Abnormalities During Induction Period | From start of study intervention on Day 1 up to Week 12 | 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. |
| Percentage of Participants Achieving Mucosal Healing at Week 12: Induction Period | Week 12 | Mucosal healing was defined as complete absence of ulcers. |
| Percentage of Participants Achieving CMEI at Week 64 Among Participants Who Achieved CMEI Response at Week 12 (Baseline of OLE Period): OLE Period | Week 64 (Week 52 of 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. |
| 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 | Week 64 (Week 52 of 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. |
| Percentage of Participants Achieving Endoscopic Remission (SES-CD Score of <= 2) at Week 12: Induction Period | Week 12 | 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. |
| Number of Participants According to Categorization of Vital Signs During Induction Period | From start of study intervention on Day 1 up to Week 12 | 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). |
| Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During Induction Period | From start of study intervention on Day 1 up to Week 12 | 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) During Induction Period | From start of study intervention on Day 1 up to Week 12 | 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. |
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During Induction Period | From start of study intervention on Day 1 up to Week 12 | 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. |
| Number of Participants Discontinuation Due to Adverse Events During Induction Period | From start of study intervention on Day 1 up to Week 12 | 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. |
| Number of Participants With Serious Infections During Induction Period | From start of study intervention on Day 1 up to Week 12 | 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). |
Countries
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, United States
Participant flow
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.
Pre-assignment details
A total of 645 participants were screened across 26 countries of which 401 were screen failures and 244 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 79 |
| 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. | 93 |
| Induction Period: Brepocitinib 60 mg QD Participants received PF-06700841 (brepocitinib) 60 mg QD orally for 12 weeks in induction period. | 72 |
| Total | 244 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Induction Period (Up to 12 Weeks) | Adverse Event | 6 | 4 | 4 | 0 | 0 | 0 | 0 |
| Induction Period (Up to 12 Weeks) | Lack of Efficacy | 2 | 0 | 2 | 0 | 0 | 0 | 0 |
| Induction Period (Up to 12 Weeks) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Induction Period (Up to 12 Weeks) | No longer meets eligibility criteria | 0 | 2 | 1 | 0 | 0 | 0 | 0 |
| Induction Period (Up to 12 Weeks) | Other | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period (Up to 12 Weeks) | Withdrawal by Subject | 2 | 2 | 0 | 0 | 0 | 0 | 0 |
| OLE Period (Up to 52 Weeks) | Adverse Event | 0 | 0 | 0 | 7 | 13 | 4 | 15 |
| OLE Period (Up to 52 Weeks) | Lack of Efficacy | 0 | 0 | 0 | 5 | 11 | 3 | 5 |
| OLE Period (Up to 52 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| OLE Period (Up to 52 Weeks) | No longer met eligibility criteria | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| OLE Period (Up to 52 Weeks) | Other | 0 | 0 | 0 | 0 | 2 | 0 | 2 |
| OLE Period (Up to 52 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 3 | 11 | 3 | 8 |
Baseline characteristics
| Characteristic | Induction Period: Placebo QD | Induction Period: Ritlecitinib 200 mg/50 mg QD | Induction Period: Brepocitinib 60 mg QD | Total |
|---|---|---|---|---|
| Age, Continuous | 36.1 Years STANDARD_DEVIATION 13.03 | 34.6 Years STANDARD_DEVIATION 10.64 | 36.5 Years STANDARD_DEVIATION 12.7 | 35.6 Years STANDARD_DEVIATION 12.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants | 91 Participants | 69 Participants | 235 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 6 Participants | 7 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 71 Participants | 84 Participants | 61 Participants | 216 Participants |
| Sex: Female, Male Female | 37 Participants | 41 Participants | 29 Participants | 107 Participants |
| Sex: Female, Male Male | 42 Participants | 52 Participants | 43 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 79 | 0 / 93 | 0 / 72 | 0 / 36 | 0 / 84 | 0 / 32 | 0 / 64 |
| other Total, other adverse events | 20 / 79 | 20 / 93 | 17 / 72 | 29 / 36 | 34 / 84 | 19 / 32 | 31 / 64 |
| serious Total, serious adverse events | 6 / 79 | 4 / 93 | 4 / 72 | 6 / 36 | 10 / 84 | 5 / 32 | 16 / 64 |
Outcome results
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 \[bpm\]).
Time frame: From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; value < 50 (mmHg) | 0 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; change >= 30 (mmHg) increase | 1 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; value < 90 (mmHg) | 0 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; change >=20 (mmHg) increase | 4 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; change >= 30 (mmHg) decrease | 3 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; change >=20 (mmHg) decrease | 1 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During OLE Period | PR; value > 120 (bpm) | 0 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; change >= 30 (mmHg) increase | 2 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | PR; value > 120 (bpm) | 1 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; change >=20 (mmHg) decrease | 4 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; value < 90 (mmHg) | 2 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; change >= 30 (mmHg) decrease | 0 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; change >=20 (mmHg) increase | 6 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; value < 50 (mmHg) | 2 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | PR; value > 120 (bpm) | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; value < 50 (mmHg) | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; change >=20 (mmHg) increase | 2 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; change >=20 (mmHg) decrease | 3 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; value < 90 (mmHg) | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; change >= 30 (mmHg) increase | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; change >= 30 (mmHg) decrease | 3 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; change >=20 (mmHg) decrease | 8 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; change >= 30 (mmHg) decrease | 2 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; change >= 30 (mmHg) increase | 5 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; change >=20 (mmHg) increase | 6 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | DBP; value < 50 (mmHg) | 1 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | SBP; value < 90 (mmHg) | 1 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants According to Categorization of Vital Signs During OLE Period | PR; value > 120 (bpm) | 0 Participants |
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.
Time frame: From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During OLE Period | 0 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During OLE Period | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During OLE Period | 0 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During OLE Period | 1 Participants |
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.
Time frame: From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Population: SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Discontinuations Due to Adverse Events During OLE Period | Discontinuation from study due to TEAEs | 0 Participants |
| Induction Period: Placebo QD | Number of Participants With Discontinuations Due to Adverse Events During OLE Period | Permanent discontinuation from any study intervention due to TEAEs | 7 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Discontinuations Due to Adverse Events During OLE Period | Permanent discontinuation from any study intervention due to TEAEs | 13 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Discontinuations Due to Adverse Events During OLE Period | Discontinuation from study due to TEAEs | 1 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Discontinuations Due to Adverse Events During OLE Period | Discontinuation from study due to TEAEs | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Discontinuations Due to Adverse Events During OLE Period | Permanent discontinuation from any study intervention due to TEAEs | 4 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants With Discontinuations Due to Adverse Events During OLE Period | Discontinuation from study due to TEAEs | 0 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants With Discontinuations Due to Adverse Events During OLE Period | Permanent discontinuation from any study intervention due to TEAEs | 15 Participants |
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.
Time frame: From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Laboratory Test Abnormalities During OLE Period | 33 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Laboratory Test Abnormalities During OLE Period | 76 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Laboratory Test Abnormalities During OLE Period | 26 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants With Laboratory Test Abnormalities During OLE Period | 56 Participants |
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.
Time frame: From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Population: SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During OLE Period | 32 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During OLE Period | 58 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During OLE Period | 25 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During OLE Period | 54 Participants |
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.
Time frame: From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Population: SAS included all those participants who received at least one dose of the investigational drug (ritlecitinib, brepocitinib, or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During OLE Period | 6 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During OLE Period | 10 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During OLE Period | 5 Participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During OLE Period | 16 Participants |
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.
Time frame: Week 12
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Period: Placebo QD | 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 | 12.8 Percentage of participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | 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 | 27.2 Percentage of participants |
| Induction Period: Brepocitinib 60 mg QD | 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 | 33.8 Percentage of participants |
p-value: 0.011990% CI: [4, 24.5]Min risk weight method(Mehrotra-Railkar)
p-value: 0.001290% CI: [10, 32.9]Min risk weight method(Mehrotra-Railkar)
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.
Time frame: Baseline and Week 12
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Induction Period: Placebo QD | Mean Change From Baseline in SES-CD Score at Week 12: Induction Period | -0.1 Units on a scale |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Mean Change From Baseline in SES-CD Score at Week 12: Induction Period | -3.1 Units on a scale |
| Induction Period: Brepocitinib 60 mg QD | Mean Change From Baseline in SES-CD Score at Week 12: Induction Period | -5.0 Units on a scale |
p-value: 0.000790% CI: [-4.55, -1.48]ANCOVA
p-value: <0.000190% CI: [-6.62, -3.26]ANCOVA
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).
Time frame: From start of study intervention on Day 1 up to Week 12
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Diastolic blood pressure; change >=20 (mmHg) increase | 4 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Systolic blood pressure; value < 90 (mmHg) | 0 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Pulse rate; value > 120 (bpm) | 4 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Diastolic blood pressure; value < 50 (mmHg) | 1 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Systolic blood pressure; change >= 30 (mmHg) decrease | 0 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Systolic blood pressure; change >= 30 (mmHg) increase | 3 Participants |
| Induction Period: Placebo QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Diastolic blood pressure; change >=20 (mmHg) decrease | 4 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Pulse rate; value > 120 (bpm) | 1 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Diastolic blood pressure; value < 50 (mmHg) | 0 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Diastolic blood pressure; change >=20 (mmHg) increase | 2 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Diastolic blood pressure; change >=20 (mmHg) decrease | 2 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Systolic blood pressure; value < 90 (mmHg) | 3 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Systolic blood pressure; change >= 30 (mmHg) increase | 2 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Systolic blood pressure; change >= 30 (mmHg) decrease | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Systolic blood pressure; value < 90 (mmHg) | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Diastolic blood pressure; change >=20 (mmHg) increase | 4 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Systolic blood pressure; change >= 30 (mmHg) decrease | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Systolic blood pressure; change >= 30 (mmHg) increase | 7 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Pulse rate; value > 120 (bpm) | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Diastolic blood pressure; change >=20 (mmHg) decrease | 4 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants According to Categorization of Vital Signs During Induction Period | Diastolic blood pressure; value < 50 (mmHg) | 0 Participants |
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.
Time frame: From start of study intervention on Day 1 up to Week 12
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Induction Period: Placebo QD | Number of Participants Discontinuation Due to Adverse Events During Induction Period | Discontinuations from study due to TEAEs | 0 Participants |
| Induction Period: Placebo QD | Number of Participants Discontinuation Due to Adverse Events During Induction Period | Permanent discontinuations from any study intervention due to TEAEs | 6 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants Discontinuation Due to Adverse Events During Induction Period | Discontinuations from study due to TEAEs | 1 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants Discontinuation Due to Adverse Events During Induction Period | Permanent discontinuations from any study intervention due to TEAEs | 4 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants Discontinuation Due to Adverse Events During Induction Period | Discontinuations from study due to TEAEs | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants Discontinuation Due to Adverse Events During Induction Period | Permanent discontinuations from any study intervention due to TEAEs | 4 Participants |
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.
Time frame: From start of study intervention on Day 1 up to Week 12
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During Induction Period | 1 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During Induction Period | 0 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During Induction Period | 0 Participants |
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.
Time frame: From start of study intervention on Day 1 up to Week 12
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Laboratory Test Abnormalities During Induction Period | 67 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Laboratory Test Abnormalities During Induction Period | 72 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Laboratory Test Abnormalities During Induction Period | 61 Participants |
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).
Time frame: From start of study intervention on Day 1 up to Week 12
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Serious Infections During Induction Period | 0 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Serious Infections During Induction Period | 1 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Serious Infections During Induction Period | 2 Participants |
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.
Time frame: From start of study intervention on Day 1 up to Week 12
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During Induction Period | 51 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During Induction Period | 46 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During Induction Period | 49 Participants |
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.
Time frame: From start of study intervention on Day 1 up to Week 12
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Period: Placebo QD | Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During Induction Period | 6 Participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During Induction Period | 4 Participants |
| Induction Period: Brepocitinib 60 mg QD | Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During Induction Period | 4 Participants |
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.
Time frame: Week 12
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Period: Placebo QD | Percentage of Participants Achieving >=25% Reduction in SES-CD From Baseline (SES-CD 25) at Week 12: Induction Period | 25.6 Percentage of participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Percentage of Participants Achieving >=25% Reduction in SES-CD From Baseline (SES-CD 25) at Week 12: Induction Period | 39.1 Percentage of participants |
| Induction Period: Brepocitinib 60 mg QD | Percentage of Participants Achieving >=25% Reduction in SES-CD From Baseline (SES-CD 25) at Week 12: Induction Period | 56.3 Percentage of participants |
p-value: 0.027990% CI: [2.1, 25.6]Min risk weight method(Mehrotra-Railkar)
p-value: <0.000190% CI: [19.1, 43.9]Min risk weight method(Mehrotra-Railkar)
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.
Time frame: Week 64 (Week 52 of OLE period)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Period: Placebo QD | Percentage of Participants Achieving CMEI at Week 64 Among Participants Who Achieved CMEI Response at Week 12 (Baseline of OLE Period): OLE Period | 27.3 Percentage of participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Percentage of Participants Achieving CMEI at Week 64 Among Participants Who Achieved CMEI Response at Week 12 (Baseline of OLE Period): OLE Period | 44.1 Percentage of participants |
| Induction Period: Brepocitinib 60 mg QD | Percentage of Participants Achieving CMEI at Week 64 Among Participants Who Achieved CMEI Response at Week 12 (Baseline of OLE Period): OLE Period | 54.5 Percentage of participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | Percentage of Participants Achieving CMEI at Week 64 Among Participants Who Achieved CMEI Response at Week 12 (Baseline of OLE Period): OLE Period | 42.1 Percentage of participants |
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.
Time frame: Week 12
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Period: Placebo QD | Percentage of Participants Achieving Endoscopic Remission (SES-CD Score of <= 2) at Week 12: Induction Period | 5.1 Percentage of participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Percentage of Participants Achieving Endoscopic Remission (SES-CD Score of <= 2) at Week 12: Induction Period | 7.6 Percentage of participants |
| Induction Period: Brepocitinib 60 mg QD | Percentage of Participants Achieving Endoscopic Remission (SES-CD Score of <= 2) at Week 12: Induction Period | 12.7 Percentage of participants |
p-value: 0.292290% CI: [-4.3, 9.3]Min risk weight method(Mehrotra-Railkar)
p-value: 0.044990% CI: [-0.4, 15.2]Min risk weight method(Mehrotra-Railkar)
Secondary
Percentage of Participants Achieving Mucosal Healing at Week 12: Induction Period
Mucosal healing was defined as complete absence of ulcers.
Time frame: Week 12
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Period: Placebo QD | Percentage of Participants Achieving Mucosal Healing at Week 12: Induction Period | 5.1 Percentage of participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | Percentage of Participants Achieving Mucosal Healing at Week 12: Induction Period | 10.9 Percentage of participants |
| Induction Period: Brepocitinib 60 mg QD | Percentage of Participants Achieving Mucosal Healing at Week 12: Induction Period | 16.9 Percentage of participants |
p-value: 0.099890% CI: [-1.6, 13.3]Min risk weight method(Mehrotra-Railkar)
p-value: 0.011190% CI: [2.8, 20.9]Min risk weight method(Mehrotra-Railkar)
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.
Time frame: Week 64 (Week 52 of OLE period)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction Period: Placebo QD | 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-CD 25 | 25.0 Percentage of participants |
| Induction Period: Placebo QD | 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-CD 50 | 25.0 Percentage of participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | 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-CD 50 | 36.4 Percentage of participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | 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-CD 25 | 41.9 Percentage of participants |
| Induction Period: Brepocitinib 60 mg QD | 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-CD 25 | 54.5 Percentage of participants |
| Induction Period: Brepocitinib 60 mg QD | 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-CD 50 | 50.0 Percentage of participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | 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-CD 25 | 42.1 Percentage of participants |
| OLE Period: Brepocitinib 60 mg QD -> Brepocitinib 30 mg QD | 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-CD 50 | 36.4 Percentage of participants |
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.
Time frame: Week 12
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Period: Placebo QD | 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 | 29.5 Percentage of participants |
| Induction Period: Ritlecitinib 200 mg/50 mg QD | 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 | 42.4 Percentage of participants |
| Induction Period: Brepocitinib 60 mg QD | 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 | 57.7 Percentage of participants |
p-value: 0.03990% CI: [1, 25.7]Min risk weight method(Mehrotra-Railkar)
p-value: 0.000190% CI: [17.2, 42.2]Min risk weight method(Mehrotra-Railkar)