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

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Trial ID: NCT03395184

Purpose

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.

Official Title

A PHASE 2A, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ORAL PF-06651600 AND PF-06700841 AS INDUCTION AND OPEN LABEL EXTENSION TREATMENT IN SUBJECTS WITH MODERATE TO SEVERE CROHN'S DISEASE

Stanford Investigator(s)

Sarah Streett
Sarah Streett

Clinical Professor, Medicine - Gastroenterology & Hepatology

Eligibility


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.

Intervention(s):

drug: Placebo PF-06700841

drug: PF-06651600

drug: PF-06700841

drug: PF-06651600 Placebo

Recruiting

I'm Interested

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Adrian Ekelmans
650-721-8436