A PHASE 2A, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ORAL PF-06651600 AND PF-06700841 AS INDUCTION AND OPEN LABEL EXTENSION TREATMENT IN SUBJECTS WITH MODERATE TO SEVERE CROHN'S DISEASE
A PHASE 2A, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ORAL PF-06651600 AND PF-06700841 AS INDUCTION AND OPEN LABEL EXTENSION TREATMENT IN SUBJECTS WITH MODERATE TO SEVERE CROHN'S DISEASE
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.
Inclusion Criteria:
Male and/or female subjects 18 years to 75 years of age
Documented diagnosis of ileal, ileocolonic, or colonic CD with a minimum disease duration of 3 months, as determined by endoscopic and histopathology assessment.
Endoscopic confirmation of active disease with total SES CD total score of at least 7. For isolated ileal disease, SES CD total score should be at least 4.
An average daily liquid/soft stool frequency (SF) greater than or equal to 2.5 or daily abdominal pain (AP) greater than or equal to 2.0.
Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for CD:
•Steroids; Immunosuppressants (azathioprine [AZA], 6 MP, or methotrexate [MTX]); Anti TNF inhibitors (infliximab, adalimumab,certolizumab); Anti integrin inhibitors (eg, vedolizumab); Anti IL 12/23 inhibitor (ustekinumab).
Subjects currently receiving the following treatment for CD are eligible providing they have been on stable doses as described below:
Exclusion Criteria:
Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, diverticular disease, ulcerative colitis (UC), or clinical findings suggestive of UC.
Presence of active (draining) fistulae or intra abdominal or perineal abscesses.
Strictures with obstructive symptoms.
Short bowel syndrome.
History of bowel perforation requiring surgical intervention within the past 12 months.
Previous bowel surgery resulting in an existing stoma. Subjects who have a j pouch are excluded, as a j pouch can result in a stoma.
History of bowel surgery within 6 months prior to baseline.
Subjects displaying clinical signs of fulminant colitis or toxic megacolon.
Subjects with primary sclerosing cholangitis.
Subjects with evidence of colonic adenomas, dysplasia or neoplasia.
Abnormal findings on the chest x ray film such as presence of tuberculosis (TB), general infections, heart failure, or malignancy.
Any history of either untreated or inadequately treated latent or active TB infection, current treatment for active or latent TB infection or evidence of currently active TB by chest x ray, residing with or frequent close contact with individual(s) with active TB.
Subjects receiving the following therapies within the time period described below or expected to receive any of these therapies during the study period:
>9 mg/day of oral budesonide or >25 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 2 weeks prior to baseline.
IV, IM (parenteral), or topical (rectal) treatment of 5 ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline.
Azathioprine, 6 mercaptopurine, or methotrexate within 2 weeks prior to baseline.
Anti TNF inhibitors (or biosimilars thereof) as described below:
Anti integrin inhibitors (eg, vedolizumab) within 8 weeks prior to baseline.
Ustekinumab within 8 weeks prior to baseline.
Interferon therapy within 8 weeks prior to baseline.
Subjects with prior treatment with lymphocyte depleting agents/therapies within 1 year prior to baseline (eg, CamPath[alemtuzumab], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc).
Subjects who have received rituximab or other selective B lymphocyte depleting agents within 1 year prior to baseline.
Subjects previously receiving leukocyte apheresis, including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline.
Other marketed immunosuppressants or biologics with immunomodulatory properties within 3 months prior to baseline.
Subjects who have received other JAK inhibitors within 3 months prior to baseline.
Subjects who have not responded to or have been intolerant of other JAK inhibitors.
Other investigational procedures(s) or product(s), such as immunosuppressants used in transplantation (eg, mycophenolate mofetil, cyclosporine, rapamycin, or tacrolimus) or live (attenuated) vaccine within 30 days prior to baseline.
14) Subjects with history of thrombotic event(s), including deep venous thrombosis (DVT), and known inherited conditions that predispose to hypercoagulability.
Redwood City, California 94063, United States
New York, New York 10021, United States
New York, New York 10065, United States
New York, New York 10065, United States
New York, New York 10065, United States
New York, New York 10065, United States
North Massapequa, New York 11758-1853, United States
Southlake, Texas 76092, United States
Liége, 4000, Belgium
Banja Luka, 78000, Bosnia and Herzegovina
Winnipeg, Manitoba R3A 1R9, Canada
Tbilisi, 0112, Georgia
Rozzano, Milan 20089, Italy
El Chouf, Lebanon
Strzegom, Lower Silesian Voivodeship 58-150, Poland
Piotrkow Tryunalski, 91-300, Poland
Poznan, 60-848, Poland
Poznan, 61-731, Poland
Moscow, 119435, Russia
Saint Petersburg, 194354, Russia
Saint Petersburg, 197706, Russia
Samara, 443029, Russia
Zrenjanin, Srbija 23000, Serbia
Chernivtsi, 58001, Ukraine
Kharkiv, 61037, Ukraine
Kyiv, 04078, Ukraine
Kyiv, 04107, Ukraine
Lviv, 79007, Ukraine