Study To Evaluate The Efficacy And Safety Of Oral PF-06651600 And PF-06700841 In Subjects With Moderate To Severe Crohn's Disease
- Conditions
- Crohn's Disease
- Interventions
- Registration Number
- NCT03395184
- Lead Sponsor
- Pfizer
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 244
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Male and/or female subjects 18 years to 75 years of age
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Documented diagnosis of ileal, ileocolonic, or colonic CD with a minimum disease duration of 3 months, as determined by endoscopic and histopathology assessment.
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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.
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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.
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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.
-
Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, diverticular disease, ulcerative colitis (UC), or clinical findings suggestive of UC.
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Presence of active (draining) fistulae or intra abdominal or perineal abscesses.
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Strictures with obstructive symptoms.
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Short bowel syndrome.
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History of bowel perforation requiring surgical intervention within the past 12 months.
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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.
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History of bowel surgery within 6 months prior to baseline.
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Subjects displaying clinical signs of fulminant colitis or toxic megacolon.
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Subjects with primary sclerosing cholangitis.
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Subjects with evidence of colonic adenomas, dysplasia or neoplasia.
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Abnormal findings on the chest x ray film such as presence of tuberculosis (TB), general infections, heart failure, or malignancy.
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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.
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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.
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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.
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Ustekinumab within 8 weeks prior to baseline.
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Interferon therapy within 8 weeks prior to baseline.
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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).
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Subjects who have received rituximab or other selective B lymphocyte depleting agents within 1 year prior to baseline.
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Subjects previously receiving leukocyte apheresis, including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline.
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Other marketed immunosuppressants or biologics with immunomodulatory properties within 3 months prior to baseline.
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Subjects who have received other JAK inhibitors within 3 months prior to baseline.
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Subjects who have not responded to or have been intolerant of other JAK inhibitors.
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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.
- Subjects with history of thrombotic event(s), including deep venous thrombosis (DVT), and known inherited conditions that predispose to hypercoagulability.
-
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-06700841 or placebo Placebo PF-06700841 - PF-06700841 or placebo PF-06700841 - PF-06651600 or placebo PF-06651600 Placebo - PF-06651600 or placebo PF-06651600 -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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).
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.
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.
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.
Trial Locations
- Locations (186)
Regional Municipal Non-profit Enterprise "Chernivtsi Regional Clinical Hospital", Surgery Department
🇺🇦Chernivtsi, Ukraine
Dothan Surgery Center
🇺🇸Dothan, Alabama, United States
Gut P.C., dba Digestive Health Specialists of the Southeast
🇺🇸Dothan, Alabama, United States
Brighton Surgical Center
🇺🇸Beverly Hills, California, United States
Entertainment Medical Group
🇺🇸Los Angeles, California, United States
Gastrointestinal Biosciences Clinical Trials, LLC
🇺🇸Los Angeles, California, United States
Stanford Medicine Outpatient Center - Digestive Health Center
🇺🇸Redwood City, California, United States
Front Range Endoscopy Center
🇺🇸Colorado Springs, Colorado, United States
Peak Gastroenterology Associates
🇺🇸Colorado Springs, Colorado, United States
Gastro Florida
🇺🇸Clearwater, Florida, United States
West Coast Endoscopy Center
🇺🇸Clearwater, Florida, United States
UF Health Jacksonville - Gastroenterology Emerson
🇺🇸Jacksonville, Florida, United States
Millenia Surgery Center
🇺🇸Orlando, Florida, United States
HMD Research LLC
🇺🇸Orlando, Florida, United States
Treasure Valley Medical Research
🇺🇸Boise, Idaho, United States
WestGlen Gastrointestinal Consultants, P.A.
🇺🇸Shawnee Mission, Kansas, United States
Chevy Chase Endoscopy Center
🇺🇸Chevy Chase, Maryland, United States
MGG Group Co., Inc., Chevy Chase Clinical Research
🇺🇸Chevy Chase, Maryland, United States
Capitol Research
🇺🇸Rockville, Maryland, United States
Brigham and Women's Hospital
🇺🇸Chestnut Hill, Massachusetts, United States
Mass Eye and Ear, Longwood
🇺🇸Boston, Massachusetts, United States
Clinical Research Institute of Michigan, LLC
🇺🇸Chesterfield, Michigan, United States
Eastside Endoscopy Center
🇺🇸Macomb, Michigan, United States
Weill Cornell Medical College - New York Presbyterian Hospital
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
New York Presbyterian Hospital - Weill Cornell Medical College (Colonoscopy)
🇺🇸New York, New York, United States
New York Presbyterian Hospital - Weill Cornell Medical College Investigational Pharmacy
🇺🇸New York, New York, United States
Weill Cornell Medical College - New York Presbyterian Hospital (Endoscopy Suite)
🇺🇸New York, New York, United States
DiGiovanna Institute for Medical Education And Research
🇺🇸North Massapequa, New York, United States
UNC Hospitals
🇺🇸Chapel Hill, North Carolina, United States
UNC Hospitals Endoscopy Center at Meadowmont
🇺🇸Chapel Hill, North Carolina, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
UNC GI Procedures Hillsborough
🇺🇸Hillsborough, North Carolina, United States
Gastroenterology Associates of the Piedmont, PA
🇺🇸Winston-Salem, North Carolina, United States
PMG Research of Winston-Salem, LLC
🇺🇸Winston-Salem, North Carolina, United States
Holston Medical Group
🇺🇸Kingsport, Tennessee, United States
Holston Valley Surgery Center
🇺🇸Kingsport, Tennessee, United States
Vanderbilt GI Endoscopy Lab at One Hundred Oaks
🇺🇸Nashville, Tennessee, United States
Vanderbilt Inflammatory Bowel Disease Clinic
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
First Street Hospital
🇺🇸Bellaire, Texas, United States
First Street Surgical Center
🇺🇸Bellaire, Texas, United States
Hermann Drive Surgical Hospital
🇺🇸Houston, Texas, United States
Pearland Surgery Center
🇺🇸Houston, Texas, United States
GI Alliance
🇺🇸Southlake, Texas, United States
Lonestar Endoscopy, LLP
🇺🇸Southlake, Texas, United States
Texas Digestive Disease Consultants (Administrative, Regulatory)
🇺🇸Southlake, Texas, United States
Gastroenterology Associates of Northern VA
🇺🇸Fairfax, Virginia, United States
Gastroenterology Associates of Northern Virginia
🇺🇸Fairfax, Virginia, United States
Verity Research, Inc.
🇺🇸Fairfax, Virginia, United States
Blue Ridge Medical Research
🇺🇸Lynchburg, Virginia, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Mater Misericordiae Ltd
🇦🇺South Brisbane, Queensland, Australia
Ballarat Base Hospital
🇦🇺Ballarat, Victoria, Australia
Saint John of God Health Care Inc.
🇦🇺Subiaco, Western Australia, Australia
AKH Wien Universitaetsklinik fuer Innere Medizin III
🇦🇹Wien, Austria
University Hospital Brussels
🇧🇪Jette, Belgium
University Hospitals Leuven
🇧🇪Leuven, Belgium
CHC MontLégia
🇧🇪Liége, Belgium
Javna zdravstvena ustanova Univerzitetski klinicki centar Republike Srpske,
🇧🇦Banja Luka, Bosnia and Herzegovina
Winnipeg Regional Health Authority - Health Sciences Centre, Winnipeg
🇨🇦Winnipeg, Manitoba, Canada
Klinicki Bolnicki centar Split, Zavod za gastroenterologiju
ðŸ‡ðŸ‡·Split, Croatia
Klinicka bolnica Dubrava Zagreb
ðŸ‡ðŸ‡·Zagreb, Croatia
Klinicki bolnicki centar Zagreb, Zavod za gastroenterologiju i hepatologiju
ðŸ‡ðŸ‡·Zagreb, Croatia
Nemocnice Horovice, a.s.
🇨🇿Horovice, Czechia
Hepato-Gastroenterologie HK s.r.o.
🇨🇿Hradec Kralove, Czechia
Medialpharma s.r.o.
🇨🇿Hradec Kralove, Czechia
MUDr. GREGAR s.r.o.
🇨🇿Olomouc, Czechia
Nemocnice Strakonice, a.s., Interni oddeleni
🇨🇿Strakonice, Czechia
Nemocnice Strakonice, a.s.
🇨🇿Strakonice, Czechia
LTD "Acad. F. Todua Medical Center - LTD Research Institute of Clinical Medicine"
🇬🇪Tbilisi, Georgia
The First University Clinic of TSMU
🇬🇪Tbilisi, Georgia
Institute of Clinical Cardiology, Ltd.
🇬🇪Tbilisi, Georgia
Paian MED Research GmbH
🇩🇪Berlin, Germany
Krankenhaus Waldfriede e.V.,
🇩🇪Berlin, Germany
Universitaetsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Bekes Megyei Kozponti Korhaz, Rethy Pal Tagkorhaz
ðŸ‡ðŸ‡ºBekescsaba, Hungary
Semmelweis Egyetem, II. Belgyogyaszati Klinika
ðŸ‡ðŸ‡ºBudapest, Hungary
Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak
ðŸ‡ðŸ‡ºBudapest, Hungary
Clinfan Szolgaltato Kft.
ðŸ‡ðŸ‡ºSzekszard, Hungary
IRCCS Saverio de Bellis
🇮🇹Castellana Grotte, Bari, Italy
A.O.Spedali Civili
🇮🇹Brescia, BS, Italy
Univ. "Magna Graecia" di Catanzaro
🇮🇹Catanzaro, CZ, Italy
ASST Monza
🇮🇹Monza, MB, Italy
Istituto Clinico Humanitas IRCCS - Sez. Autonoma di Malattie, Infiammatorie Croniche Intestinali
🇮🇹Rozzano, Milan, Italy
A.O.U. Policlinico G. Martino
🇮🇹Messina, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Policlinico Universitario Campus Bio-Medico
🇮🇹Roma, Italy
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Korea, Republic of
Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
Saint George Hospital University Medical Center
🇱🇧Achrafieh, Lebanon
American University of Beirut Medical Center
🇱🇧Beirut, Lebanon
Ain Wazein Medical Village
🇱🇧El Chouf, Lebanon
Hammoud Hospital University Medical Center
🇱🇧Saida, Lebanon
STRZEGOMSKIE CENTRUM MEDYCZNO-DIAGNOSTYCZNE Sp. z o.o.
🇵🇱Strzegom, Dolnoslaskie, Poland
DC-MED Sp. z o.o. Sp.k.
🇵🇱Swidnica, Other, Poland
H-T. Centrum Medyczne-Endoterapia
🇵🇱Tychy, Silesia, Poland
Niepubliczny Zaklad Opieki Zdrowotnej All-Medicus
🇵🇱Katowice, Poland
ETG Kielce
🇵🇱Kielce, Poland
Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla
🇵🇱Knurow, Poland
Szpital w Knurowie Sp. z o.o.
🇵🇱Knurow, Poland
Samodzielny Publiczny Zespół Opieki Zdrowotnej, Pracownia Endoskopii
🇵🇱Koscian, Poland
Centrum Medyczne Szpital Swietej Rodziny Sp z o.o.
🇵🇱Lodz, Poland
Pracownia Endoskopii Centrum Medyczne Szpital Swietej Rodziny Sp z o.o.
🇵🇱Lodz, Poland
Ośrodek Badań Klinicznych Appletreeclinics
🇵🇱Lodz, Poland
SALVE
🇵🇱Lodz, Poland
Gastromed Sp. z o.o.
🇵🇱Lublin, Poland
IRMED
🇵🇱Piotrkow Trybunalski, Poland
Samodzielny Szpital Wojewodzki im. M. Kopernika w Piotrkowie Trybunalskim
🇵🇱Piotrkow Tryunalski, Poland
PRZYCHODNIA SPECJALISTYCZNA MEDIC-R Clinical Research Center Spolka z ograniczona odpowiedzialnoscia
🇵🇱Poznan, Poland
Ai Centrum Medyczne Sp. Z O.O. Sp.K.
🇵🇱Poznan, Poland
AM-MEDIC SP. z o.o.
🇵🇱Poznan, Poland
Gabinety Lekarskie Rivermed
🇵🇱Poznan, Poland
KO-MED Centra Kliniczne
🇵🇱Pulawy, Poland
Zaklad Opieki Zdrowotnej Medical Sp. z o.o., (endoscopy)
🇵🇱Pulawy, Poland
ENDOSKOPIA Sp. z o. o.
🇵🇱Sopot, Poland
Szpital Sredzki Serca Jezusowego sp. z o.o.
🇵🇱Sroda Wielkopolska, Poland
Nowe Zdrowie-CK, Kiełtucki i Wspólnicy Sp.j.
🇵🇱Staszow, Poland
Twoja Przychodnia Szczecinskie Centrum Medyczne
🇵🇱Szczecin, Poland
SONOMED
🇵🇱Szczecin, Poland
Centrum Zdrowia MDM
🇵🇱Warszawa, Poland
WIP Warsaw IBD Point Profesor Kierkus
🇵🇱Warszawa, Poland
Endoterapia PFG Sp. z o.o.
🇵🇱Warszawa, Poland
Centrum Diagnostyczno-Lecznicze Barska Sp. z o. o.
🇵🇱Wloclawek, Poland
Futuremeds
🇵🇱Wroclaw, Poland
Melita Medical Sp. z o.o.
🇵🇱Wroclaw, Poland
Centrum Gastrologiczno Hepatologiczne
🇵🇱Wroclaw, Poland
Lexmedica
🇵🇱Wroclaw, Poland
Golden Care
🇵🇱Wroclaw, Poland
Private Medical Institution "Euromedservice"
🇷🇺Pushkin, Saint-petersburg, Russian Federation
SPb SBIH "City Hospital #40 of the Kurortnyi region"
🇷🇺Saint-Petersburg, Sestroretsk, Russian Federation
Polyclinic Ultrasound 4D LLC
🇷🇺Pyatigorsk, Stavropol Region, Russian Federation
LLC "Alliance Biomedical-Ural Group"
🇷🇺Izhevsk, Russian Federation
LLC "Olla-Med"
🇷🇺Moscow, Russian Federation
Sechenov University on the base of Institute of Translational Medicine and Biotechnology
🇷🇺Moscow, Russian Federation
Limited Liability Company "Medical Center SibNovoMed"
🇷🇺Novosibirsk, Russian Federation
Novosibirskiy Gastrocenter
🇷🇺Novosibirsk, Russian Federation
Clinic at FSBEI HE "Omsk State Medical University" MoH RF
🇷🇺Omsk, Russian Federation
LLC "New Clinic"
🇷🇺Pyatigorsk, Russian Federation
LLC "Research center Eco-Safety"
🇷🇺Saint Petersburg, Russian Federation
Limited Liability Company "Medical Center "Reavita Med SPb" (OOO "MC "RM SPb")
🇷🇺Saint-Petersburg, Russian Federation
Limited Liability Company "RIAT"
🇷🇺Saint-Petersburg, Russian Federation
Limited Liability Company "RIAT SPb"
🇷🇺Saint-Petersburg, Russian Federation
Private Institution Educational Organization of Higher Education
🇷🇺Samara, Russian Federation
Non-state Healthcare Institution 'Railway Clinical Hospital at Samara Station of Open Joint Stock
🇷🇺Samara, Russian Federation
Limited Liability Company Medical Company "Hepatolog"
🇷🇺Samara, Russian Federation
Saint-Petersburg State Budgetary Healthcare Institution "City Clinical Hospital of the Righteous
🇷🇺St. Petersburg, Russian Federation
State Budgetary Healthcare Institution of the Stavropol Region
🇷🇺Stavropol, Russian Federation
King AbdulAziz Medical City
🇸🇦Riyadh, Saudi Arabia
King Khalid University Hospital
🇸🇦Riyadh, Saudi Arabia
Klinicko Bolnicki Centar "Bezanijska Kosa"
🇷🇸Zemun, Beograd, Serbia
Klinicki Centar Kragujevac
🇷🇸Kragujevac, Srbija, Serbia
Opsta bolnica Subotica
🇷🇸Subotica, Srbija, Serbia
Opsta Bolnica "Djordje Joanovic", Odeljenje Interno, Odsek Gastroenterologija
🇷🇸Zrenjanin, Srbija, Serbia
KBC "Dr Dragisa Misovic-Dedinje"
🇷🇸Beograd, Serbia
Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
🇸🇰Banska Bystrica, Slovakia
ENDOMED, s.r.o.
🇸🇰Vranov nad Toplou, Slovakia
Wits Clinical Research Trial Site
🇿🇦Parktown, Gauteng, South Africa
Dr Wright Private Practice
🇿🇦Claremont, Western CAPE, South Africa
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Universitario Fundacion Alcorcon
🇪🇸Alcorcon, Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Universitätsspital Zürich
🇨ðŸ‡Zürich, Switzerland
La Rabta Hospital
🇹🇳Tunis, Tunisia
Habib Thameur Hospital
🇹🇳Tunis, Tunisia
Hacettepe Universitesi Tip Fakultesi
🇹🇷Ankara, Turkey
Kocaeli Universitesi Tip Fakultesi
🇹🇷Kocaeli, Turkey
Mersin Universitesi Tip Fakultesi Hastanesi, Ic Hastaliklari
🇹🇷Mersin, Turkey
Mersin Universitesi Tip Fakultesi Hastanesi
🇹🇷Mersin, Turkey
Bulent Ecevit Universitesi Tip Fakultesi
🇹🇷Zonguldak, Turkey
Municipal Healthcare Institution Kharkiv City Clinical Hospital #2 n.a. prof. O.O. Shalimov
🇺🇦Kharkiv, Ukraine
Medical Centre Medical Clinic Blagomed LLC
🇺🇦Kyiv, Ukraine
Medical Center "OK Clinic+" of International Institute of Clinical Trials
🇺🇦Kyiv, Ukraine
Medical Center "Universal clinic Oberig" of "Kapital" LLC, Gastro center
🇺🇦Kyiv, Ukraine
Municipal Non-profit enterprise of Kyiv Regional Council "Kyiv regional hospital"
🇺🇦Kyiv, Ukraine
Municipal non-profit enterprise of Kyiv regional council "Kyiv regional clinical hospital"
🇺🇦Kyiv, Ukraine
Lviv clinical hospital on Railway Transport of Health Care Center branch of PJSC Ukrainian Railway
🇺🇦Lviv, Ukraine
Vinnytsia City Clinical Hospital No.1
🇺🇦Vinnytsia, Ukraine
Private Small-Scale Enterprise Medical Center "Pulse"
🇺🇦Vinnytsia, Ukraine
Vinnytsia Regional Clinical Hospital for War Veterans
🇺🇦Vinnytsia, Ukraine
Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrohov
🇺🇦Vinnytsia, Ukraine
Medical Center "DIACENTER"LLC
🇺🇦Zaporizhzhia, Ukraine
Emirates Specialty Hospital
🇦🇪Dubai, United Arab Emirates