E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe atopic dermatitis |
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E.1.1.1 | Medical condition in easily understood language |
Atopic dermatitis is also known as atopic eczema. It is a type of inflammation of the skin that results in itchy, red, swollen, and cracked Skin. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of PF 04965842 compared with placebo when co administered with background medicated topical therapy in adolescent participants 12 to <18 years of age with moderate-to-severe AD. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of PF 04965842 co administered with background medicated topical therapy on additional efficacy endpoints and patient reported outcomes over time in adolescent participants 12 to <18 years of age with moderate to severe AD.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A STUDY OF IMMUNOGENICITY FOLLOWING ADMINISTRATION OF TETANUS, DIPHTHERIA AND ACELLULAR PERTUSSIS COMBINATION VACCINE (TDAP) IN ADOLESCENT PARTICIPANTS 12 TO <18 YEARS OF AGE WITH MODERATE TO SEVERE ATOPIC DERMATITIS RECEIVING PF 04965842 OR PLACEBO
Version 13 Sep 2018
Objective:
To evaluate the effect of PF 04965842 on immunogenicity to Tdap vaccine in adolescent participants 12 to < 18 years of age with moderate to severe AD.
Endpoints (as secondary endpoints for study B7451036)
• Mean fold increase from baseline in concentrations of IgG against tetanus toxoid, diphtheria toxoid, pertussis toxoid, pertactin (PRN), filamentous hemagglutinin (FHA), and fimbriae types 2 and 3 (FIM) at 4 weeks post vaccination.
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E.3 | Principal inclusion criteria |
Age
1. Participant must be 12 to < 18 years of age, inclusive, at the time of
signing the informed consent.
Type of Participant and Disease Characteristics
2. Participants who meet the following AD criteria:
•Confirmed diagnosis of AD at the screening and baseline visits
according to Hanafin and Rajka criteria for AD.
•Documentation of any of the following:
•Inadequate response to treatment with medicated topical therapy for
AD for at least 4 consecutive weeks, within 6 months before the
screening visit; or
•Treatment with systemic therapy for AD within 6 months before the
screening visit; or
•Participant is a candidate for systemic therapy for AD.
NOTE: Medicated topical therapy is defined as a topical product that
contains an active pharmaceutical ingredient indicated for the treatment
of AD (irrespective of whether it is an over-the-counter [OTC] or
prescribed product).
• Moderate -to -severe AD (must fulfil all of the following criteria:
affected BSA ≥10%, IGA ≥3, EASI ≥16, and Peak Pruritus NRS ≥4 at the
baseline visit).
3. During the last 7 days prior to Day 1, for the treatment of AD, the
subject must have used only non-medicated topical therapy (ie,
emollient) at least twice daily, without other active ingredients indicated
to treat AD, or other additives which could affect AD (eg, hyaluronic acid,
urea, ceramide or filaggrin degradation products), with response to
treatment remaining inadequate at baseline. The participant must also
be willing and able to comply with standardized background topical
therapy, as per protocol guidelines, throughout the remainder of the
study.
4. Must agree to avoid prolonged exposure to the sun and not to use
tanning booths, sun lamps or other ultraviolet light sources during the
study.
5. If receiving concomitant medications for any reason other than AD,
must be on a stable regimen, which is defined as not starting a new drug
or changing dosage within 7 days or 5 half lives (whichever is longer)
prior to Day 1 and through the duration of the study.
Weight
6. Body weight ≥ 25 kg.
Sex
7. Male or Female
Contraception use by men or women should be consistent with local
regulations regarding the methods of contraception for those
participating in clinical studies.
a. Male participants:
No contraceptive measures required.
b. Female participants:
A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
• Is not a woman of childbearing potential (WOCBP)
OR
• Is a WOCBP (all female participants, regardless of whether or not they
have experienced/reported menarche, are considered WOCBP unless
they are permanently sterile or confirmed infertile). A WOCBP who is
sexually active must use a contraceptive method that is highly effective,
with a failure rate of <1%, as described in Appendix 4 during the
intervention period and for at least 28 days after the last dose of study
intervention. The investigator should evaluate the effectiveness of the
contraceptive method in relationship to the first dose of study
intervention.
• A WOCBP must have a negative highly sensitive serum pregnancy test
at the screening visit. A urine pregnancy test with a sensitivity of at
least 25 mIU/mL, will be performed before the first dose of study
intervention and at every site visit including the EOT and follow up visits
to confirm the subject has not become pregnant. If a urine test cannot
be confirmed as negative (eg, an ambiguous result), a serum pregnancy
test is required. In such cases, the participant must be excluded from
participation if the serum pregnancy result is positive.
• The investigator is responsible for review of medical history, menstrual
history, and recent sexual activity to decrease the risk for inclusion of a
woman with an early undetected pregnancy.
Informed Consent
8. Capable of giving signed informed consent/assent as described
Appendix in which includes compliance with the requirements and
restrictions listed in the informed consent form (ICF) and in this
protocol.
9. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. |
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E.4 | Principal exclusion criteria |
Medical Conditions
1. Other acute or chronic medical or laboratory abnormality that may
increase the risk associated with study participation or study
intervention administration or may interfere with the interpretation of
study results and, in the judgment of the investigator, would make the
participant inappropriate for entry into this study.
2. Any psychiatric condition including recent or active suicidal ideation or
behavior that meets any of the criteria listed in the study protocol.
3. A current or past medical history of conditions associated with
thrombocytopenia, coagulopathy or platelet dysfunction.
4. Currently have active forms of other inflammatory skin diseases, ie,
not AD or have evidence of skin conditions at the time of Day 1 that
would interfere with evaluation of AD or response to treatment.
5. Have a history of any lymphoproliferative disorder such as Epstein
Barr virus (EBV)-related lymphoproliferative disorder, history of
lymphoma, leukemia, or signs or symptoms suggestive of current
lymphatic or lymphoid disease.
6. Infection History as indicated in the study protocol.
7. Have a history of alcohol or substance abuse within 6 months prior to
Day 1 that in the opinion of the investigator will preclude participation in
the study.
8. Have a known immunodeficiency disorder or a first degree relative
with a hereditary immunodeficiency.
9. Have any malignancies or have a history of malignancies with the
exception of adequately treated or excised non metastatic basal cell or
squamous cell cancer of the skin, or cervical carcinoma in situ.
10. Have evidence of active or latent or inadequately treated infection
with Mycobacterium tuberculosis (TB) as evidenced by any of the listed
in the protocol.
Prior/Concomitant Therapy
11. Require treatment with prohibited concomitant medication(s) or
have received a prohibited concomitant medication within the specified
time frame prior to the first dose of study medication.
12. Receiving anti coagulants or medications known to cause
thrombocytopenia, (unless considered safe to stop and washout for the
duration of the study).
13. Vaccinated or exposed to a live or attenuated vaccine within the 6
weeks prior to the first dose of study intervention, or is expected to be
vaccinated or to have household exposure to these vaccines during
treatment or during the 6 weeks following discontinuation of study
intervention.
14. Participants without documentation confirming prior varicella-zoster
infection (chickenpox) or documented evidence of having received at
least one dose of the varicella vaccine in countries where the vaccine is
approved and standard of care or those who do not have evidence of
prior exposure to varicella zoster virus (VZV) based on serological
testing (ie, varicella zoster virus immunoglobulin G antibody [VZV IgG
Ab]) at screening.
15. Participants who have received prior treatment with systemic JAK
inhibitors.
16. Have received any of the following treatment regimens specified in
the timeframes outlined below:
Within 1 year of first dose of study intervention:
• As indicated in the protocol
Within 12 weeks of first dose of study intervention:
• As indicated in the protocol
Within 4 weeks of first dose of study intervention:
• As indicated in the protocol
Within 1 week of first dose of study intervention:
• As indicated in the protocol
Prior/Concurrent Clinical Study Experience
17. Participation in other studies involving investigational drug(s) within
8 weeks or within 5 half lives (if known) whichever is longer, prior to
study entry and/or during study participation.
Note: Any investigational or experimental therapy taken or procedure
performed for AD, psoriasis, psoriatic arthritis or rheumatoid arthritis in
the previous 1 year should be discussed with the Pfizer clinician (or
designee). Participants cannot participate in studies of other
investigational or experimental therapies or procedures at any time
during their participation in this study.
Diagnostic assessments
18. ANY of the abnormalities listed in the protocol in the clinical
laboratory tests at screening, as assessed by the study specific
laboratory and confirmed by a single repeat, if deemed necessary
For details and other exclusion criteria please see the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Response based on the Investigator's Global Assessment (IGA) score of clear (0) or almost clear (1) (on a 5 point scale) and a reduction from baseline of greater or equel 2 points at Week 12;
• Response based on the Eczema Area and Severity Index greater or equel 75% improvement from baseline (EASI 75) response at Week 12.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key Secondary Endpoints
• Response based on at least 4 points improvement in the Peak Pruritus NRS from baseline at Weeks 2, 4, and 12;
• Change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) total score at Week 12.
Secondary Efficacy Endpoints
• Response based on at least 4 points improvement in the Peak Pruritus NRS from baseline at all scheduled time points other than Weeks 2, 4 and 12;
• Time to achieve at least 4 points improvement in the Peak Pruritus NRS from baseline by Day 15;
• Response based on the EASI 75 at all scheduled time points except Week 12;
• Response based on the IGA of clear (0) or almost clear (1) and 2 point reduction from baseline at all scheduled time points except Week 12.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 2, 4, and 12 and day 15 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
China |
Japan |
Mexico |
Taiwan |
United States |
Latvia |
Poland |
Spain |
Czechia |
Germany |
Italy |
Hungary |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 18 |