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Study Evaluating Efficacy and Safety of PF-04965842 and Dupilumab in Adult Subjects With Moderate to Severe Atopic Dermatitis on Background Topical Therapy (JADE Compare)

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ClinicalTrials.gov Identifier: NCT03720470
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
B7451029 is a Phase 3 study to investigate PF-04965842 in adult patients who have moderate to severe atopic dermatitis and use background topical therapy. The efficacy of two dosage strengths of PF-04965842, 100 mg and 200 mg taken orally once daily will be evaluated relative to placebo over 12 weeks. The efficacy of the two dosage strengths of PF-04965842 will be compared with dupilumab in terms of pruritus relief at 2 weeks. The two dosage strengths of PF-04965842 and dupilumab 300 mg injected subcutaneously once every two weeks (with a loading dose of 600 mg injected on the first day) will also be evaluated relative to placebo over 16 weeks. The safety of the investigational products will be evaluated over the duration of the study. Subjects will use non-medicated emollient at least twice a day and medicated topical therapy such as corticosteroids, calcineurin inhibitors or PDE4 inhibitors, as per protocol guidance, to treat active lesions during the study. Subjects who are randomized to receive one of the two dosage strengths of PF-04965842 will also receive placebo injectable study drug every two weeks until Week 16 and then will continue on receiving only the oral study drug for 4 weeks. Subjects who are randomized to receive dupilumab injections every two weeks will also receive oral placebo to be taken once daily until Week 16 and will then continue to receive only the oral placebo for 4 weeks. Subjects who are randomized to the placebo arms, will receive both daily oral placebo and injectable placebo every two weeks until Week 16, after which they will receive either 100 mg or 200 mg of PF-04965842 taken orally once daily for 4 weeks, dependent upon which arm they have been allocated to. Eligible subjects will have an option to enter a long-term extension study after completing 20 weeks of treatment.

Condition or disease Intervention/treatment Phase
Dermatitis Dermatitis, Atopic Eczema Skin Diseases Skin Diseases, Genetic Genetic Diseases, Inborn Skin Diseases, Eczematous Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Drug: PF-04965842 100 mg Drug: PF-04965842 200 mg Drug: Dupilumab Drug: Oral Placebo Drug: Injectable Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 700 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 AND DUPILUMAB IN COMPARISON WITH PLACEBO IN ADULT SUBJECTS ON BACKGROUND TOPICAL THERAPY, WITH MODERATE TO SEVERE ATOPIC DERMATITIS
Actual Study Start Date : October 29, 2018
Estimated Primary Completion Date : February 2, 2020
Estimated Study Completion Date : February 2, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema
Drug Information available for: Dupilumab

Arm Intervention/treatment
Experimental: PF-04965842 100 mg + Placebo Inj followed by PF-04965842 100mg
Once-daily oral PF-04965842 100 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 100 mg from Week 16 to Week 20
Drug: PF-04965842 100 mg

PF-04965842 100 mg, administered as two tablets to be taken orally once daily as follows:

  1. In the arm "PF-04965842 100 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 100 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
  2. In the arm "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" subjects take PF-04965842 100 mg from Week 16 to Week 20.

Drug: Injectable Placebo
Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16.

Experimental: PF-04965842 200 mg + Placebo Inj followed by PF-04965842 200mg
Once-daily oral PF-04965842 200 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 200 mg from Week 16 to Week 20
Drug: PF-04965842 200 mg

PF-04965842 200 mg, administered as two tablets to be taken orally once daily as follows:

  1. In the arm "PF-04965842 200 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 200 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
  2. In the arm "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842" subjects take PF-04965842 200 mg from Week 16 to Week 20.

Drug: Injectable Placebo
Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16.

Active Comparator: Dupilumab Injection + Oral Placebo followed by Oral Placebo
Dupilumab injected subcutaneously once every 2 weeks + once-daily oral Placebo from Day 1 until Week 16 followed by once-daily oral Placebo from Week 16 to Week 20
Drug: Dupilumab
Two subcutaneous injections of Dupilumab 300 mg as a loading dose administered on Day 1 (for a total of 600 mg) followed by one injection once every two weeks (q2w) until Week 16.

Drug: Oral Placebo

Oral placebo (for PF-04965842) administered as two tablets to be taken orally once daily as follows:

  1. In the arm "Dupilumab Injection + Oral Placebo followed by Oral Placebo," the Oral Placebo is taken together with Dupilumab from Day 1 until Week 16, then by itself to Week 20;
  2. In the arms "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" and "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842," subjects, take Oral Placebo from Day 1 until Week 16.

Placebo Comparator: Oral Placebo + Placebo Inj followed by 100 mg PF-04965842
Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 100 mg PF-04965842 from Week 16 to Week 20
Drug: PF-04965842 100 mg

PF-04965842 100 mg, administered as two tablets to be taken orally once daily as follows:

  1. In the arm "PF-04965842 100 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 100 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
  2. In the arm "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" subjects take PF-04965842 100 mg from Week 16 to Week 20.

Drug: Oral Placebo

Oral placebo (for PF-04965842) administered as two tablets to be taken orally once daily as follows:

  1. In the arm "Dupilumab Injection + Oral Placebo followed by Oral Placebo," the Oral Placebo is taken together with Dupilumab from Day 1 until Week 16, then by itself to Week 20;
  2. In the arms "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" and "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842," subjects, take Oral Placebo from Day 1 until Week 16.

Drug: Injectable Placebo
Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16.

Placebo Comparator: Oral Placebo + Placebo Inj followed by 200 mg PF-04965842
Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 200 mg PF-04965842 from Week 16 to Week 20
Drug: PF-04965842 200 mg

PF-04965842 200 mg, administered as two tablets to be taken orally once daily as follows:

  1. In the arm "PF-04965842 200 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 200 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
  2. In the arm "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842" subjects take PF-04965842 200 mg from Week 16 to Week 20.

Drug: Oral Placebo

Oral placebo (for PF-04965842) administered as two tablets to be taken orally once daily as follows:

  1. In the arm "Dupilumab Injection + Oral Placebo followed by Oral Placebo," the Oral Placebo is taken together with Dupilumab from Day 1 until Week 16, then by itself to Week 20;
  2. In the arms "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" and "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842," subjects, take Oral Placebo from Day 1 until Week 16.

Drug: Injectable Placebo
Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16.




Primary Outcome Measures :
  1. Investigator's Global Assessment (IGA) [ Time Frame: Baseline, Week 12 ]
    Response based on achieving the IGA of clear (0) or almost clear (1) (on a 5 point scale) and a reduction from baseline (predose Day 1) of >=2 points at Week 12.

  2. Eczema Area and Severity Index (EASI) [ Time Frame: Baseline, Week 12 ]
    Response based on achieving the EASI-75 (>=75% improvement from baseline) at Week 12.


Secondary Outcome Measures :
  1. Pruritus Numerical Rating Scale (NRS) [ Time Frame: Baseline, Week 2 ]
    Response based on achieving at least 4 points improvement in the severity of Pruritus NRS from baseline at Week 2.

  2. Investigator's Global Assessment (IGA) [ Time Frame: Baseline, Week 16 ]
    Response based on achieving the IGA of clear (0) or almost clear (1) (on a 5 point scale) and a reduction from baseline (predose Day 1) of >=2 points at Week 16.

  3. Eczema Area and Severity Index (EASI) [ Time Frame: Baseline, Week 16 ]
    Response based on achieving the EASI-75 (>=75% improvement from baseline) at Week 16.

  4. Investigator's Global Assessment (IGA) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 18, Week 20, Week 24 (follow up) ]
    Response based on achieving the IGA of clear (0) or almost clear (1) (on a 5 point scale) and >=2 point reduction from baseline at all scheduled time points except Week 12 and Week 16.

  5. Eczema Area and Severity Index (EASI) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 18, Week 20, Week 24 (follow up). ]
    Response based on achieving a >=75% improvement in the EASI total score (EASI 75) at all scheduled time points except Week 12 and Week 16.

  6. Eczema Area and Severity Index (EASI) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24 (follow up) ]
    Response based on achieving a >=50%, >=90%, and 100% improvement in the EASI total score (EASI 50, EASI 90, and EASI-100) at all scheduled time points.

  7. Pruritus Numerical Rating Scale (NRS) [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24 (follow up) ]
    Response based on achieving at least 4 points improvement in the severity of Pruritus NRS from baseline at all scheduled time points except Week 2.

  8. Pruritus Numerical Rating Scale (NRS) [ Time Frame: Baseline to Week 24 (follow up) ]
    Time from baseline to achieve at least 4 points improvement in the severity of Pruritus NRS scale.

  9. Body Surface Area (BSA) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24 (follow up) ]
    Change from baseline in the percentage Body Surface Area (BSA) affected at all scheduled time points.

  10. Patient Global Assessment (PtGA) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24 (follow up) ]
    Change from baseline of Patient Global Assessment (PtGA) at all scheduled time points.

  11. Dermatology Life Quality Index (DLQI) [ Time Frame: Baseline, Week 2, Week 12, Week 16, Week 20, Week 24 (follow up) ]
    Change from baseline in Dermatology Life Quality Index (DLQI) at all scheduled time points.

  12. EuroQol Quality of Life 5 Dimension 5 Level Scale (EQ 5D 5L) [ Time Frame: Baseline, Week 12, Week 16, Week 20, Week 24 (follow up) ]
    Change from baseline in EuroQol Quality of Life 5 Dimension 5 Level Scale (EQ 5D 5L) at all scheduled time points.

  13. Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline, Week 12, Week 16, Week 20 ]
    Change from baseline in Hospital Anxiety and Depression Scale (HADS) at all scheduled time points.

  14. Patient Oriented Eczema Measure (POEM) [ Time Frame: Baseline, Week 12, Week 16, Week 20 ]
    Change from baseline in Patient Oriented Eczema Measure (POEM) at all scheduled time points.

  15. Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24 (follow up) ]
    Change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) total score at all scheduled time points.

  16. Scoring Atopic Dermatitis (SCORAD) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24 (follow up) ]
    Response based on a >=50% and >=75% improvement in SCORAD (SCORAD50, SCORAD75) from baseline at all scheduled time points.

  17. Scoring Atopic Dermatitis (SCORAD) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24 (follow up) ]
    Change from baseline at all scheduled time points in SCORAD subjective assessments of itch and sleep loss.

  18. Steroid-free days [ Time Frame: Baseline, Week 24 (follow up) ]
    Steroid free days at Week 16.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects aged 18 years or older at the time of informed consent
  • Diagnosis of atopic dermatitis (AD) for at least 1 year and current status of moderate to severe disease (>= the following scores: BSA 10%, IGA 3, EASI 16, Pruritus NRS severity 4)
  • Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with medicated topical therapy for AD for at least 4 weeks, or who have required systemic therapies for control of their disease.
  • Must be willing and able to comply with standardized background topical therapy, as per protocol guidelines throughout the study
  • Female subjects who are of childbearing potential must not be intending to become pregnant, currently pregnant, or lactating. The following conditions apply:

    1. Female subjects of childbearing potential must have a confirmed negative pregnancy test prior to randomization;
    2. Female subjects of childbearing potential must agree to use a highly effective method of contraception for the duration of the active treatment period and for at least 28 days after the last dose of investigational product.
  • Female subjects of non-childbearing potential must meet at least 1 of the following criteria:

    • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    • Have medically confirmed ovarian failure; or
    • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.

All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.

-If receiving concomitant medications for any reason other than AD, must be on a stable regimen prior to Day 1 and through the duration of the study

Exclusion Criteria:

  • Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
  • Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q wave interval abnormalities, current or history of certain infections, cancer, lymphoproliferative disorders and other medical conditions at the discretion of the investigator
  • Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
  • Other active nonAD inflammatory skin diseases or conditions affecting skin
  • Prior treatment with JAK inhibitors
  • Previous treatment with dupilumab
  • Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03720470


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

  Show 218 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03720470     History of Changes
Other Study ID Numbers: B7451029
COMPARE ( Other Identifier: Alias Study Number )
2018-002573-21 ( EudraCT Number )
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:
atopic dermatitis
atopic eczema
eczema
JAK
janus kinase

Additional relevant MeSH terms:
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Dermatitis
Dermatitis, Atopic
Eczema
Hypersensitivity
Skin Diseases
Genetic Diseases, Inborn
Immune System Diseases
Hypersensitivity, Immediate
Skin Diseases, Genetic
Skin Diseases, Eczematous
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs