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

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.

Condition

  • Crohn's Disease

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts 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:
  14. >9 mg/day of oral budesonide or >25 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 2 weeks prior to baseline.
  15. IV, IM (parenteral), or topical (rectal) treatment of 5 ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline.
  16. Azathioprine, 6 mercaptopurine, or methotrexate within 2 weeks prior to baseline.
  17. Anti TNF inhibitors (or biosimilars thereof) as described below:
  18. Infliximab within 8 weeks prior to baseline;
  19. Adalimumab within 8 weeks prior to baseline;
  20. Certolizumab within 8 weeks prior to baseline;
  21. Anti integrin inhibitors (eg, vedolizumab) within 8 weeks prior to baseline.
  22. Ustekinumab within 8 weeks prior to baseline.
  23. Interferon therapy within 8 weeks prior to baseline.
  24. 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).
  25. Subjects who have received rituximab or other selective B lymphocyte depleting agents within 1 year prior to baseline.
  26. Subjects previously receiving leukocyte apheresis, including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline.
  27. Other marketed immunosuppressants or biologics with immunomodulatory properties within 3 months prior to baseline.
  28. Subjects who have received other JAK inhibitors within 3 months prior to baseline.
  29. Subjects who have not responded to or have been intolerant of other JAK inhibitors.
  30. 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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
PF-06700841 or placebo
  • Drug: Placebo PF-06700841
    12 weeks, followed by PF-06700841, 30 mg QD for 52 weeks.
  • Drug: PF-06700841
    60 mg QD for 12 weeks followed by 30 mg QD for up to 52 weeks
Experimental
PF-06651600 or placebo
  • Drug: Placebo PF-06651600
    12 weeks, followed by PF-06651600, 50 mg QD for 52 weeks
  • Drug: PF-06651600
    200 mg QD for 8 weeks, followed by 50 mg QD up to 56 weeks

Recruiting Locations

Vanderbilt University Medical Center - GI Endoscopy Lab
Nashville, Tennessee 37232-5543

Vanderbilt University Medical Center - GI Research Regulatory
Nashville, Tennessee 37232

Vanderbilt University Medical Center
Nashville, Tennessee 37232-7610

Vanderbilt University Medical Center
Nashville, Tennessee 37212-1610

Vanderbilt University Medical Center
Nashville, Tennessee 37212-1375

More Details

NCT ID
NCT03395184
Status
Recruiting
Sponsor
Pfizer

Study Contact

Pfizer CT.gov Call Center
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com