Primary Objective• To estimate the long term safety of 100 mg and 200 mg once daily (QD) of abrocitinib with or without topical treatments in adult and adolescent subjects who previously participated in qualifying abrocitinib atopic dermatitis (AD)…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints
• The incidence of treatment emergent adverse events.
• The incidence of serious adverse events and adverse events leading to
discontinuation.
• The incidence of clinical abnormalities and change from baseline in clinical
laboratory values, ECG measurements, and vital signs.
Secondary outcome
Secondary endpoints
Baseline, for efficacy endpoints, is defined as pre dose Day 1 in the relevant
qualifying parent study.
• Response based on achieving 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 >=2 points at all scheduled time points.
• Response based on achieving >=50%, >=75%, >=90% and 100% improvement from
baseline in the Eczema Area and Severity Index (EASI) total score (EASI50,
EASI75, EASI90 and EASI100) at all scheduled time points.
• Response based on achieving an improvement >=4 points from baseline in the
severity of pruritus numerical rating scale (NRS) at all scheduled time points.
• Change from baseline in the frequency of itching due to Atopic Dermatitis
• Change from baseline of Patient Global Assessment (PtGA) at all scheduled
time points.
• Change from baseline in the percentage Body Surface Area (BSA) affected at
all scheduled time points.
• Change from baseline in Dermatology Life Quality Index (DLQI) or Children*s
DLQI (CDLQI) at all scheduled time points.
• Change from baseline in Patient Oriented Eczema Measure (POEM) at all
scheduled time points.
• Change from baseline in Hospital Anxiety and Depression Scale (HADS) at all
scheduled time points.
• Change from baseline in European Quality of Life 5 Dimension 5 Level Scale
(EQ 5D 5L) or European Quality of Life 5 Dimension Youth Scale (EQ 5D Y) at all
scheduled time points.
• Steroid-free Days at all scheduled time points.
• Serum hsCRP levels at all scheduled time points.
Background summary
Atopic dermatitis, also known as atopic eczema, is a common, chronic,
inflammatory skin disorder characterized by flaky skin lesions, intense
pruritus, and a general deterioration in the quality of life. Over the past 50
years, AD has become more prevalent, especially in industrialized, temperate
countries such as the US. AD is one of the most common, chronic, relapsing
childhood dermatoses, impacting 15 30% of all children in the US and many have
disease that persists into adulthood with a lifetime prevalence of those
affected in childhood reported to be 34%
There are a limited number of treatments available for AD and those that are
available have multiple limitations. The topical therapies have drawbacks
related to the duration of use due to the potential for local and systemic side
effects and to the body regions of use. For AD patients not responding to
topical therapies and phototherapy, off label use of systemic agents, which
include oral corticosteroids or oral immunosuppressants, remain the last viable
treatment option. Systemic therapy options are associated with potentially
severe adverse effects and require careful monitoring. The risk of toxicity
and side effects remain a concern when systemic agents are used. For these
reasons the use of these agents is limited to short courses or intermittent
therapy.
Therefore, the predominant unmet medical need is for a conveniently
administrered therapy with an acceptable safety profile for long term
continuous and intermittent use which is effective for moderate to severe AD
not controlled with topical therapies. Abrocitinib is provided as an orally
administered tablet, which is a more convenient treatment for patients with
moderate to severe AD.
Abrocitinib is an orally bioavailable small molecule that selectively inhibits
JAK1 by blocking the ATP binding site. A variety of pro inflammatory cytokines
such as IL 4, IL 13, IL 22, IL 31 and IFN-gamma , have been suggested to have a
role in the pathogenesis of AD. Many of these pathogenic cytokines use the
JAK1 for signaling. Therefore, JAK1 is an attractive therapeutic target for AD
as an innovative oral therapeutic agent.
Study objective
Primary Objective
• To estimate the long term safety of 100 mg and 200 mg once daily (QD) of
abrocitinib with or without topical treatments in adult and adolescent subjects
who previously participated in qualifying abrocitinib atopic dermatitis (AD)
Phase 3 trials.
Secondary Objectives
• To estimate the long term efficacy of abrocitinib.
Study design
This is a multicenter, long-term extension study to evaluate the long term
safety and efficacy of abrocitinib administered to subjects aged 12 years and
older with moderate to severe AD. Subjects must have completed a qualifying
parent study and remain eligible to receive abrocitinib, or have completed the
full rescue treatment/open-label run-in period of B7451014 and failed to meet
the protocol defined response criteria at week 12. Based on treatment
assignment, abrocitinib will be administered orally at doses of 200 mg or 100
mg once daily (QD). The maximum total treatment duration for individual
subjects may differ, as this will be variable; The duration of the study for
adults who remain eligible and active in the study will be until at least 2024;
The duration of the study for adolescents who remain eligible and active in the
study will be until they reach 18 years of age, or until 2024, whichever is
later. After these time points, as relevant, a subject may continue to receive
Investigational
Product in this LTE) study at the discretion of the sponsor regardless of
availability of commercial product in their country, or until the sponsor
terminates the study in that country (see Section 14). Subjects will enter a 4
week follow up period after permanent discontinuation of treatment. Medicated
and non-medicated topical treatments for AD are permitted throughout the
study. Systemic treatments for AD are prohibited throughout the study.
Concomitant medication for adverse events or other non AD concomitant medical
conditions are permitted throughout the study, unless listed as a prohibited
medication (Appendix 18, Appendix 19).
Subjects who meet eligibility criteria for this long term extension study will
undergo screening/baseline/Day -1 assessments (as required per the Schedule of
Activities). Subjects previously randomized to either dose of active
investigational product, either abrocitinib 200 mg or 100 mg QD in the
qualifying parent study will be allocated to the same dose in this long-term
extension study, and the blind will be maintained throughout Treatment Period
1. Subjects previously randomized to active control drug or placebo only in a
qualifying parent study will be randomized to double-blind treatment in this
long-term extension study during Treatment Period 1; either abrocitinib 200 mg
or 100 mg QD. For exceptions please see the protocol.
Open-label drug will be provided to all subjects in Treatment Period 2, in line
with their previously allocated dose.
Intervention
All subjects receive either 100 or 200 mg abrocitinib daily.
Study burden and risks
Please refer to appendix D of the subject information sheet for an overview of
the side effects and possible risks of the study.
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Listed location countries
Age
Inclusion criteria
1. Evidence of a personally signed and dated informed consent document
indicating that the subject or their parent(s)/legal guardian, if applicable,
have been informed of all pertinent aspects of the study.
2. Male or female subjects of 12 years of age or older, at the time of informed
consent and meets inclusion criterion for minimum body weight (if applicable)
from qualifying parent study. Adolescent subjects below the age of 18 years old
(or country-specific age of majority) will only be enrolled in this study if
instructed by the sponsor and approved by the country or regulatory/health
authority. If these approvals have not been granted, only subjects aged 18
years (or country-specific age of majority) and older will be enrolled.
3. Willing and able to comply with scheduled visits, treatment plan, laboratory
tests and other study procedures.
4. Must have completed the full treatment period of a qualifying parent study
OR must have completed the full rescue treatment period of a qualifying parent
study (if applicable). OR must have completed the full open-label run-in period
in B7451014 and did not meet the protocol-specified response criteria at week
12.
5. Female subjects who are of childbearing potential (which includes all female
subjects aged 12 years and older, regardless of whether they have experienced
menarche) must not be intending to become pregnant, currently pregnant, or
lactating. The following conditions apply:
a. Female subjects of childbearing potential must have a confirmed negative
pregnancy test prior to allocation to treatment.
b. Female subjects of childbearing potential must agree to use a highly
effective method of contraception (as per Section 4.4.1) for the duration of
the active treatment period and for at least 28 days after the last dose of
investigational product.
For Czech Republic only, 5 b. is revised and 5 c. is added to require:
Female subjects of childbearing potential >=15 years of age who are at risk of
pregnancy 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;
c. Female subjects less than 15 years of age must not be sexually active, and
abstinence per the below definition should be confirmed prior to enrollment.
NOTE: Sexual abstinence, defined as completely and persistently refraining from
all heterosexual intercourse (including during the entire period of risk
associated with the study treatments) may obviate the need for contraception
ONLY if this is the preferred and usual lifestyle of the subject.
6. Female subjects of non-childbearing potential must meet at least 1 of the
following criteria:
a. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
b. Have medically confirmed ovarian failure; or
c. 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.
7. 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.
8. Must agree to avoid use of prohibited medications throughout the duration of
the study, as detailed in Appendix 18 and Appendix 19.
Exclusion criteria
1. 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.
2. Currently have active forms of other inflammatory skin diseases, ie, not AD
or have evidence of skin conditions (eg, psoriasis, seborrheic dermatitis,
lupus) at the time of Day -1 that would interfere with evaluation of atopic
dermatitis or response to treatment.
3. Discontinued from treatment (or rescue treatment period/open-label run-in
period, if applicable) early in a qualifying parent study OR triggered a
discontinuation criterion at any point during the qualifying parent study OR
meets exclusion criteria from qualifying parent studies which in the opinion of
the investigator, or sponsor, is an ongoing safety concern.
4. Ongoing adverse event in the qualifying parent study which in the opinion of
the investigator, or sponsor, is an ongoing safety concern.
5. Investigator site staff members directly involved in the conduct of the
study and their family members, site staff members otherwise supervised by the
investigator, or subjects who are Pfizer employees, including their family
members, directly involved in the conduct of the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-004851-22-NL |
| CCMO | NL66738.100.18 |