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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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ClinicalTrials.gov Identifier: NCT03395184
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : October 25, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE December 5, 2017
First Posted Date  ICMJE January 10, 2018
Last Update Posted Date October 25, 2019
Actual Study Start Date  ICMJE February 2, 2018
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
Proportion of subjects achieving clinically meaningful endoscopic improvement (reduction of more than or equal to 3 points from baseline in Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) at Week 12 [ Time Frame: 12 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03395184 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2018)
  • Number of participants with potentially clinically important serious infections findings [ Time Frame: 64 weeks ]
  • Mean change from baseline in SES-CD score at Week 12. [ Time Frame: Baseline, week 12 ]
  • Proportion of subjects achieving SES-CD 25 and SES-CD 50 at Week 12. [ Time Frame: Baseline, week 12 ]
    Number of subjects achieving SES-CD 25 and SES-CD 50 at Week 12.
  • Proportion of subjects achieving endoscopic remission (SES-CD less than or equal to 2) at Week 12. [ Time Frame: Week 12 ]
    Number of subjects achieving endoscopic remission (SES-CD less than or equal to 2) at Week 12.
  • Proportion of subjects achieving mucosal healing at Week 12. [ Time Frame: Week 12 ]
    Number of subjects achieving mucosal healing at Week 12.
  • Number of subjects with adverse events [ Time Frame: Baseline up to 64 weeks ]
    Number of participants with reported adverse events
  • Number of subjects with serious adverse events [ Time Frame: Baseline up to 64 weeks ]
    Number of participants with reported serious adverse events
  • Number of subjects with electrocardiogram findings of potential clinical importance. [ Time Frame: Baseline up to 64 weeks ]
    Number of participants with potentially clinically important electrocardiogram findings.
  • Number of subjects withdrawal due to adverse events [ Time Frame: Baseline up to 64 weeks ]
    Number of subjects withdrawal due to adverse events.
  • Number of subjects with vital signs findings of potential clinical importance. [ Time Frame: Baseline up to 64 weeks ]
    Number of participants with potentially clinically important vital signs findings.
  • Number of subjects with laboratory tests findings of potential clinical importance. [ Time Frame: Baseline u to 64 weeks ]
    Number of participants with potentially clinically important laboratory findings.
  • Proportion of subjects achieving SES CD 25 and SES CD 50 at Week 64 among subjects who achieved SES CD 25 and SES CD 50 at week 12 respectively. [ Time Frame: week 64 ]
    Number of subjects achieving SES-CD 25 and SES-CD 50 at Week 64 among subjects who achieved SES CD 25 and SES CD 50 at week 12
  • Proportion of subjects achieving clinically meaningful endoscopic improvement (CMEI response) at week 64 among subjects who achieved CMEI response at Week 12. [ Time Frame: week 64 ]
    Number of subject achieving clinically meaningful endoscopic improvement (CMEI response) at week 64 among subjects who achieved CMEI response at week 12.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
  • Mean change from baseline in SES-CD score at Week 12. [ Time Frame: Baseline, week 12 ]
  • Proportion of subjects achieving SES-CD 25 and SES-CD 50 at Week 12. [ Time Frame: Baseline, week 12 ]
    Number of subjects achieving SES-CD 25 and SES-CD 50 at Week 12.
  • Proportion of subjects achieving endoscopic remission (SES-CD less than or equal to 2) at Week 12. [ Time Frame: Week 12 ]
    Number of subjects achieving endoscopic remission (SES-CD less than or equal to 2) at Week 12.
  • Proportion of subjects achieving mucosal healing at Week 12. [ Time Frame: Week 12 ]
    Number of subjects achieving mucosal healing at Week 12.
  • Number of subjects with adverse events [ Time Frame: Baseline up to 64 weeks ]
    Number of participants with reported adverse events
  • Number of subjects with serious adverse events [ Time Frame: Baseline up to 64 weeks ]
    Number of participants with reported serious adverse events
  • Number of subjects withdrawal due to adverse events [ Time Frame: Baseline up to 64 weeks ]
    Number of subjects withdrawal due to adverse events.
  • Number of subjects with vital signs findings of potential clinical importance. [ Time Frame: Baseline up to 64 weeks ]
    Number of participants with potentially clinically important vital signs findings.
  • Number of subjects with laboratory tests findings of potential clinical importance. [ Time Frame: Baseline u to 64 weeks ]
    Number of participants with potentially clinically important laboratory findings.
  • Number of subjects with electrocardiogram findings of potential clinical importance. [ Time Frame: Baseline up to 64 weeks ]
    Number of participants with potentially clinically important electrocardiogram findings.
  • Number of participants with potentially clinically important serious infections findings [ Time Frame: 64 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study To Evaluate The Efficacy And Safety Of Oral PF-06651600 And PF‑06700841 In Subjects With Moderate To Severe Crohn's Disease
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE
  • Drug: Placebo PF-06651600
    12 weeks, followed by PF-06651600, 50 mg QD for 52 weeks
  • Drug: Placebo PF-06700841
    12 weeks, followed by PF-06700841, 30 mg QD for 52 weeks.
  • Drug: PF-06651600
    200 mg QD for 8 weeks, followed by 50 mg QD up to 56 weeks
  • Drug: PF-06700841
    60 mg QD for 12 weeks followed by 30 mg QD for up to 52 weeks
Study Arms  ICMJE
  • Experimental: PF-06700841 or placebo
    Interventions:
    • Drug: Placebo PF-06700841
    • Drug: PF-06700841
  • Experimental: PF-06651600 or placebo
    Interventions:
    • Drug: Placebo PF-06651600
    • Drug: PF-06651600
Publications * Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gopalsamy A, Hayward MM, Hegen M, Hollingshead BD, Jussif J, Knafels JD, Limburg DC, Lin D, Lin TH, Pierce BS, Saiah E, Sharma R, Symanowicz PT, Telliez JB, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X, Zhang L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018 Oct 11;61(19):8597-8612. doi: 10.1021/acs.jmedchem.8b00917. Epub 2018 Aug 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 3, 2018)
250
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2022
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Bosnia and Herzegovina,   Canada,   Croatia,   Czechia,   Georgia,   Germany,   Hungary,   Italy,   Korea, Republic of,   Lebanon,   Poland,   Russian Federation,   Saudi Arabia,   Serbia,   Slovakia,   South Africa,   Spain,   Switzerland,   Tunisia,   Turkey,   Ukraine,   United Arab Emirates,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03395184
Other Study ID Numbers  ICMJE B7981007
2017-003359-43 ( EudraCT Number )
PIZZICATO ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP