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

NCT03395184

Last updated date
Study Location
Axon Clinical s.r.o.
Praha 5, , 150 00, Czechia
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Crohn's Disease
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-75 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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.

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Advanced Information
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 Center1-800-718-1021[email protected]
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/d….
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d…
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date October 2020

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