Primary objective:To demonstrate the efficacy of dupilumab administered concomitantly with TCS through week 16 in adult patients with moderate-to-severe atopic dermatitis (AD).Secondary objectives:Evaluate long-term efficacy of dupilumab when…
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Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients with EASI-75 response (reduction of EASI score by >=75%
from baseline) at week 16.
Proportion of patients with both an IGA 0 or 1 (on a 5-point scale) and a
reduction from baseline of >=2 points at week 16.
Secondary outcome
Key Secondary Endpoints:
* Proportion of patients with EASI-75 response (reduction of EASI score by *75%
from baseline) at week 16 (this is not a secondary efficacy endpoint for the EU
and EU reference market countries, and Japas, as it is already a co-primary
endpoint)
* Percent change from baseline to week 16 in weekly average of peak daily
Pruritus Numerical Rating Scale (NRS)
* Proportion of patients with improvement (reduction) in weekly average of peak
daily Pruritus NRS *4 from baseline to week 16
* Proportion of patients with IGA 0 or 1 and a reduction from baseline of >=2
points at week 52
* Proportion of patients with EASI-75 response at week 52
* Proportion of patients with improvement (reduction) in weekly average of peak
daily Pruritus NRS >=3 from baseline to week 16.
* Percent change from baseline to week 52 in weekly average of peak daily
Pruritus NRS.
Other secondary endpoints:
* Percent change in EASI score from baseline to week 16.
* Change from baseline to week 16 in percent BSA
* Percent change in SCORing Atopic Dermatitis (SCORAD) from baseline to week 16
* Percent change from baseline to week 16 in Global Individual Sings Score
(GISS) (erythema, infiltration/papulation, excoriations, lichenification)
* Change from baseline to week 16 in Dermatology Life Quality Index (DLQI)
* Change from baseline to week 16 in Patient Oriented Eczema Measure (POEM)
* Change from baseline to week 16 in Hospital Anxiety and Depression Scale
(HADS)
* Reduction in topical AD medication use through week 16 (determined by the
amount of TCS and/or topical calcineurin inhibitors (TCI) used since previous
visit in weight).
* Proportion of patients with improvement (reduction) in weekly average of peak
daily Pruritus NRS *3 from baseline to week 52
* Proportion of patients with improvement (reduction) in weekly average of peak
daily Pruritus NRS *4 from baseline to week 52
* Percent change in EASI score from baseline to week 52.
* Change from baseline to week 52 in percent BSA
* Percent change in SCORAD from baseline to week 52
* Percent change from baseline to week 52 in GISS (erythema,
infiltration/papulation, excoriations, lichenification)
* Change from baseline to week 2 in weekly average of peak daily Pruritus NRS
* Number of flares through week 52
* Change from baseline to week 52 in DLQI
* Change from baseline to week 52 in POEM
* Change from baseline to week 52 in HADS
* Incidence of skin-infection treatment-emergent adverse events (TEAEs)
requiring systemic treatment from baseline through week 56
* Incidence of serious TEAEs through week 56
* Indicence of TEASs leading to study drug discontinuation from baseline
through week 56
Background summary
Atopic dermatitis (AD) is a chronic/relapsing inflammatory skin disease
characterized by intense pruritus (eg, itchiness), and by scaly and dry
eczematous lesions. It is often associated with other atopic disorders, such as
allergic rhinitis and asthma. Severe disease can be extremely disabling due to
several factors: major psychological problems, significant sleep loss, and
impaired quality of life (QOL) that leads to a high socioeconomic cost. An
estimated 15% to 30% of children and 2% to 10% of adults are affected by AD.
The goal in treating AD is reducing skin inflammation. Up-regulation of IL-4
and IL-13 has been implicated as an important inflammatory component of AD
disease progression. Dupilumab targets the IL-4R*, and thus interferes with the
signaling cascade. Inhibition of this Th2 inflammatory pathway is currently
being and has previously been evaluated with other agents.
Dupilumab is being developed for the treatment of moderate-to-severe AD in
patients intolerant of, or not adequately controlled with, topical treatments.
Phase 1 and phase 2 data with dupilumab have, to date, demonstrated promising
efficacy, safety, and tolerability in a patient population with moderate*
to-severe AD. In many cases, treatment-benefit occurred during the first week
of treatment; this early response is similar to the time of onset observed with
cyclosporine treatment, but without the apparent risk for cardiovascular and
renal side effects.
Study objective
Primary objective:
To demonstrate the efficacy of dupilumab administered concomitantly with TCS
through week 16 in adult patients with moderate-to-severe atopic dermatitis
(AD).
Secondary objectives:
Evaluate long-term efficacy of dupilumab when administered concomitantly with
TCS for up to 52 weeks.
Evaluate long-term safety of dupilumab when administered concomitantly with TCS
for up to 52 weeks.
Research objectives:
Assess the relationship between long-term exposure to dupilumab and potential
biomarkers of AD.
Study design
This is a 64-week (52-week treatment period and 12 week follow up), randomized,
double-blind, placebo-controlled, parallel group study to confirm the efficacy
and safety of dupilumab administered concomitantly with TCS in adults with
moderate-to-severe AD. After providing informed consent, patients will be
assessed for study eligibility at the screening visit. Patients will undergo
screening within 35 days prior to randomization. During the screening period,
treatments for AD will be washed out for at least 7 days prior to baseline
(except moisturizers). Patients will be required to apply moisturizers
(emollients) twice daily for at least the 7 consecutive days immediately before
randomization and continue throughout the study. However, to allow adequate
assessment of skin dryness, moisturizers should not be applied on the area(s)
of non-lesional skin designated for such assessments for at least 8 hours
before each clinic visit.
Patients who continue to meet eligibility criteria at baseline will undergo day
1/baseline assessments and will be randomized in a 3:1:3 ratio to receive qw or
q2w SC injections of 300 mg dupilumab, following a loading dose of 600 mg on
day 1 (during weeks when dupilumab is not administered, patients will receive
placebo), or matching placebo including the loading dose. In order to maintain
blinding, all patients will receive an injection each week from day 1 to week
51. Randomization will be stratified by baseline disease severity (moderate
[IGA = 3 vs. severe [IGA = 4] AD) and by region. Eligible patients must have a
documented history of inadequate response to treatment with topical AD
medication. Patients will have the option to self administer study drug
outside the study site during weeks in which no clinic visit is scheduled.
Patients (and/or caregivers) will be trained on injecting study drug at visits
2 (day 1) through visit 4 (week 2), or until competency has been demonstrated.
Patients will remain at the study site for a minimum of 30 minutes after each
of the first 3 weekly injections. Patients who do not want to self-inject may
have the clinic staff administer all the study drug injections in the clinic.
Starting on day 1/baseline, all patients will initiate treatment with TCS using
a standardized regimen and continue the standardized regimen through the end of
the study.
After week 2, if needed to control intolerable symptoms, patients will be
eligible to receive rescue treatment with any locally approved AD treatments at
the discretion of the investigator. If rescue is needed after week 2,
investigators will be encouraged to provide rescue therapy in a staged fashion,
using a greater intensity of treatment compared to that which the patient was
using (eg, increasing the potency of TCS, treating with oral corticosteroids,
systemic nonsteroid immunosuppressants, or phototherapy). Patients who
experience worsening of disease between scheduled visits should return to the
clinic (unscheduled visit) for IGA, Eczema Area and Severity Index (EASI), and
body surface area (BSA) of involvement of AD assessments before starting
treatment escalation. Patients may receive rescue after week 2 with TCS and
continue treatment with study drug. If a patient receives rescue with a
systemic nonsteroid immunosuppressant, systemic corticosteroids, or
phototherapy, the patient must stop study drug, but may be eligible to restart
treatment with study drug after discontinuing such rescue treatment. Patients
who are discontinued from study drug are considered treatment failures, but
will remain in the study and continue with the study visits and assessments.
Use of all concomitant topical products, medications, and procedures will be
documented.
The end of treatment period visit will occur at week 52, 1 week after the last
dose of study drug. The duration of the 12-week follow-up period is based on
the time expected for drug levels to reach zero (below the lower limit of
quantification) in most patients after the last dose of dupilumab. The end of
study visit will occur at week 64
Patients who complete this study may be eligible to enroll in a subsequent
open-label extension study in which they may receive treatment with dupilumab.
Safety, laboratory, and clinical assessments will be performed at specified
clinic visits as noted.
Approximately 700 patients will be enrolled.
Intervention
Subcutaneous dupilumab injection OR subcutaneous placebo injection:
Patients will receive a loading dose of 400 mg (2 injections each containing
200 mg dupilumab in a 2 mL volume) on day 1 followed by 200 mg in 2 mL qw from
week 1 through week 52.
OR
Patients will receive a loading dose of 600 mg (2 injections, each containing
300 mg dupilumab in a 2 mL volume), on day 1 followed by 300 mg in 2 mL q2w
from week 2 through week 50 (even-numbered weeks). During weeks in which
dupilumab is not administered (odd-numbered weeks), patients will receive
placebo injections (see below).
The last dose of study drug for both regimens will be at week 51.
OR
Placebo:
Matching placebo SC injection. Loading dose for the placebo arm consists of 2
injections, each containing placebo formulation in a 2 mL volume, administered
at day 1 followed by qw injections of 2 mL placebo formulation from week 1
through week 52 (last dose of study drug will be at week 51).
Study burden and risks
Dupilumab is bestudeerd bij ruim 400 menselijke proefpersonen, bestaande uit
gezonde vrijwilligers en patiënten met atopische dermatitis, astma en
neuspoliepen. Op grond van de momenteel beschikbare gegevens zijn er geen
vastgestelde risico's bepaald die rechtstreeks verband houden met dupilumab.
Patients are closely monitored on AEs, ECGs vital functions and lab results to
ensure patient safety and to support the evaluation of the safety profile.
The risks and burden for the patient are thought to be in perspective to the
treatment of the patient and the necessity to study new compounds with
additional benefits. Patients are given the choice to either go to the
researchcenter for the weekly injection or to learn to do it at home.
Old Saw Mill River Road 777
Tarrytown NY 10591
NL
Old Saw Mill River Road 777
Tarrytown NY 10591
NL
Listed location countries
Age
Inclusion criteria
1. Male or female, 18 years or older
2. Chronic AD, (according to the American Academy of Dermatology Consensus Criteria),that has been present for at least 3 years before the screening visit.
3. Patients with documented recent history (within 6 months before the screening visit) of inadequate response to a sufficient course of outpatient treatment with topical AD medication(s), or for whom topical AD therapies are medically inadvisable.
Exclusion criteria
1. Prior treatment with dupilumab.
2. Important side effects of topical medication (e.g., tolerance to treatment, hypersensitivity reactions, significant skin atrophy, systemic effects), as assessed by the investigator or patient's treating physician.
3. At baseline visit >=30% of the total lesional surface located on areas of thin skin that cannot be safely treated with medium or higher potency TCS (e.g., face, neck, intertriginous areas, genital areas, areas of skin atrophy)
4. Recent treatment (within specific time windows before the baseline visit) with systemic corticosteroids, immunosuppressive agents, topical corticosteroids and calcineurin inhibitors, live (attenuated) vaccine, other investigational drugs.
5. History of human immunodeficiency virus (HIV) infection.
6. HIV or viral hepatitis positive serology at screening.
7. Known or suspected immunosuppression
8. Recent infections requiring antiinfectious treatment
9. Recent history or high risk of clinical endoparasitoses, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization.
10. High risk populations (low life expectancy, severe concomitant diseases, etc.)
11. Pregnant or breast-feeding women
12. Patients of reproductive potential and sexually active who are unwilling to use adequate contraceptives
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003254-24-NL |
| CCMO | NL48219.018.14 |