A Phase 3 Study Investigating the Efficacy, Safety, and Tolerability of Dupilumab Administered to Adult Patients With Severe Atopic Dermatitis Who Are Not Adequately Controlled With or Are Intolerant to Oral Cyclosporine A, or When This Treatment is Not Medically Advisable
Overview
- Phase
- Phase 3
- Intervention
- Matching Placebo
- Conditions
- Atopic Dermatitis
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 325
- Locations
- 7
- Primary Endpoint
- Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The main objective of the trial is to evaluate the efficacy of 2 dose regimens of dupilumab compared to placebo, administered with concomitant topical corticosteroids (TCS), in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral Cyclosporine A (CSA), or when this treatment is currently not medically advisable.
The secondary objective is to assess the safety and tolerability of 2 dose regimens of dupilumab compared to placebo, administered with concomitant TCS, in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral CSA, or when this treatment is currently not medically advisable.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, 18 years or older
- •Severe, Chronic AD, (according to American Academy of Dermatology Consensus Criteria \[Eichenfield 2014\]) for whom treatment with potent TCS is indicated
- •EASI score ≥20 at the screening and baseline visits
- •IGA score ≥3 (on the 0 to 4 IGA scale) at the screening and baseline visits
- •≥10% body surface area (BSA) of AD involvement at the screening and baseline visits
- •Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with TCS
- •Have applied a stable dose of topical emollient (moisturizer) twice daily for at least the 7 consecutive days immediately before the baseline visit
- •Documented history by a physician of either:
- •No prior CSA exposure and not currently a candidate for CSA treatment due to:
- •medical contraindications (eg, uncontrolled hypertension on medication), or
Exclusion Criteria
- •Participation in a prior dupilumab clinical study
- •Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the screening visit
- •Hypersensitivity and/or intolerance to corticosteroids or to any other ingredients contained in the TCS product used in the study
- •Systemic CSA, systemic corticosteroids, or phototherapy within 4 weeks prior to screening, and azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or Janus kinase (JAK) inhibitors within 8 weeks prior to screening
- •Treatment with TCI within 1 week before the screening visit
- •Treatment with biologics as follows:
- •Any cell-depleting agents including but not limited to rituximab: within 6 months before the screening visit, or until lymphocyte count returns to normal, whichever is longer
- •Other biologics: within 5 half-lives (if known) or 16 weeks prior to the screening visit, whichever is longer
- •Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit
- •Treatment with a live (attenuated) vaccine within 12 weeks before the screening
Arms & Interventions
Placebo QW + TCS
Participants received one subcutaneous (SC) injection of dupilumab matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Intervention: Matching Placebo
Dupilumab 300 mg Q2W + TCS
Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Intervention: Dupilumab
Dupilumab 300 mg QW + TCS
Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).
Intervention: Dupilumab
Outcomes
Primary Outcomes
Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16
Time Frame: Baseline, Week 16
The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. The analysis population for efficacy analyses is the Full Analysis Set (FAS) which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized).
Secondary Outcomes
- Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16(Baseline, Week 16)
- Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16(Baseline, Week 16)
- Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16(Baseline, Week 16)
- Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16(Baseline, Week 16)
- Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period(Baseline to week 16)
- Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period(Baseline to Week 16)
- Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16(Baseline to Week 16)
- Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16(Baseline, Week 16)
- Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use(Baseline, Week 16)
- Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16(Baseline, Week 16)
- Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16(Baseline, Week 16)
- Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16(Baseline, Week 16)
- Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16(Baseline, Week 16)
- Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification)(Baseline, Week 16)
- Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period(Baseline to Week 16)
- Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2(Baseline, Week 2)
- Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period(Baseline to Week 16)
- Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period(Baseline to Week 16)