Study To Evaluate The Efficacy And Safety Of Oral PF-06651600 And PF-06700841 In Subjects With Moderate To Severe Crohn's Disease

Pfizer244 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

244

Conditions

Crohn's Disease

Interventions

PF-06651600 PlaceboDRUG

12 weeks, followed by PF-06651600, 50 mg once daily (QD) for 52 weeks

PF-06651600DRUG

200 mg QD for 8 weeks, followed by 50 mg QD up to 56 weeks

Placebo PF-06700841DRUG

12 weeks, followed by PF-06700841, 30 mg QD for 52 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (195)

Outcomes

Primary Outcomes

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

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)

Number of Participants According to Categorization of Vital Signs During OLE Period

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

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.