Clinical trial NCT03736967: Efficacy and Safety of REGN3500 Monotherapy and Combination of REGN3500 Plus Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Efficacy and Safety of REGN3500 Monotherapy and Combination of REGN3500 Plus Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Atopic Dermatitis
Keywords: Moderate
Severe
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2018-11-09
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the efficacy of REGN3500 monotherapy compared with placebo treatment in adult patients with moderate-to-severe Atopic dermatitis (AD).

Secondary Objectives are to:

* Evaluate the efficacy of REGN3500 in combination with dupilumab compared with placebo treatment in adult patients with moderate-to-severe AD
* Assess the safety, tolerability, and immunogenicity of subcutaneous (SC) doses of REGN3500 monotherapy and REGN3500 in combination with dupilumab in adult patients with moderate-to-severe AD
* Evaluate the Pharmacokinetic (PK) of REGN3500 monotherapy and REGN3500 in combination with dupilumab in adult patients with moderate-to-severe AD


Eligibility criteria: Key Inclusion Criteria:

1. Chronic AD, according to American Academy of Dermatology Consensus Criteria (Eichenfield, 2014), that has been present for at least 3 years before the screening visit
2. Eczema Area and Severity Index (EASI) score ≥16 at the screening and baseline visits
3. ≥10% Body surface area (BSA) of AD involvement at the screening and baseline visits
4. Documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s) or for whom topical treatments are medically inadvisable

Key Exclusion Criteria:

1. Prior participation in an anti-Interleukin (IL)-33 class antibody (including but not limited to REGN3500) or anti-IL-4Rα class antibody (including but not limited to dupilumab) clinical study; past treatment with or current treatment with dupilumab or another anti-IL-4Rα treatment
2. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit
3. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis (TB), histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per investigator judgment
4. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening
5. Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (HCV Ab) at the screening visit
6. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

Note: Other protocol defined Inclusion/Exclusion Criteria apply

Primary outcomes:
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on All Observed Values Regardless of Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieved Eczema Area and Severity Index-50 (EASI-50) (Greater Than or Equal to [≥] 50 Percent [%] Improvement From Baseline) Based on Observed Values Set to Missing After Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieved Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) Based on All Observed Values Regardless of Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieved Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) Based on Observed Values Set to Missing After Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieved Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) Based on All Observed Values Regardless of Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieved Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) Based on Observed Values Set to Missing After Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieved Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) Based on All Observed Values Regardless of Rescue Treatment at Week 16
timeFrame: Week 16
measure: Absolute Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16
timeFrame: Week 16
measure: Absolute Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on All Observed Values Regardless of Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Both Investigator Global Assessment (IGA) Score 0 or 1 (on the 0 to 5 IGA Scale) and a Reduction From Baseline of ≥2 Points Based on Observed Values Set to Missing After Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Both IGA Score 0 or 1 (on the 0 to 5 IGA Scale) and a Reduction From Baseline of ≥2 Points Based on All Observed Values Regardless of Rescue Treatment at Week 16
timeFrame: Week 16
measure: Absolute Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16
timeFrame: Week 16
measure: Absolute Change From Baseline in Weekly Average of Daily Peak Pruritus NRS Score Based on All Observed Values Regardless of Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percent Change From Baseline in in Weekly Average of Daily Peak Pruritus NRS Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percent Change From Baseline in in Weekly Average of Daily Peak Pruritus NRS Score Based on All Observed Values Regardless of Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Improvement (Reduction From Baseline) in Weekly Average of Peak Daily Pruritus NRS ≥4 Based on Observed Values Set to Missing After Rescue Treatment at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Improvement (Reduction From Baseline) in Weekly Average of Peak Daily Pruritus NRS ≥4 Based on All Observed Values Regardless of Rescue Treatment at Week 16
timeFrame: Week 16
measure: Time to Onset of Effect on Pruritus (≥4-point Reduction of Weekly Average of Daily Peak Pruritus NRS From Baseline)
timeFrame: Week 16
measure: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16
timeFrame: Week 16
measure: Absolute Change From Baseline in Percent Body Surface Area (BSA) of Atopic Dermatitis (AD) Involvement at Week 16
timeFrame: Week 16
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) From Baseline up to Week 16
timeFrame: Baseline up to Week 16
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) From Baseline up to Week 36
timeFrame: Baseline up to Week 36
measure: Number of Participants With Positive Treatment-Emergent Anti-drug Antibodies (ADA) to REGN3500 and Dupilumab
timeFrame: Baseline up to Week 36
measure: Serum Concentration of Functional REGN3500
timeFrame: Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, and 36
measure: Serum Concentration of Functional Dupilumab
timeFrame: Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, and 36
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Regeneron Research Site
state: Arizona
city: Fountain Valley
country: United States
facility: Regeneron Research Site
state: California
city: Long Beach
country: United States
facility: Regeneron Research Site
state: California
city: Los Angeles
country: United States
facility: Regeneron Research Site
state: California
city: Los Angeles
country: United States
facility: Regeneron Research Site
state: California
city: Sacramento
country: United States
facility: Regeneron Research Site
state: California
city: Davie
country: United States
facility: Regeneron Research Site
state: Florida
city: Sandy Springs
country: United States
facility: Regeneron Research Site
state: Georgia
city: Rockville
country: United States
facility: Regeneron Research Site
state: Maryland
city: Bay City
country: United States
facility: Regeneron Research Site
state: Michigan
city: Saint Joseph
country: United States
facility: Regeneron Research Site
state: Michigan
city: Troy
country: United States
facility: Regeneron Research Site
state: Michigan
city: Bronx
country: United States
facility: Regeneron Research Site
state: New York
city: Forest Hills
country: United States
facility: Regeneron Research Site
state: New York
city: New York
country: United States
facility: Regeneron Research Site
state: New York
city: New York
country: United States
facility: Regeneron Research Site
state: New York
city: High Point
country: United States
facility: Regeneron Research Site
state: North Carolina
city: Norman
country: United States
facility: Regeneron Research Site
state: Oklahoma
city: Portland
country: United States
facility: Regeneron Research Site
state: Oregon
city: Pittsburgh
country: United States
facility: Regeneron Research Site
state: Pennsylvania
city: Arlington
country: United States
facility: Regeneron Research Site
state: Texas
city: Richmond
country: United States
facility: Regeneron Research Site
state: Virginia
city: Anderlecht
country: Belgium
facility: Regeneron Research Site
city: Antwerp
country: Belgium
facility: Regeneron Research Site
city: Brussels
country: Belgium
facility: Regeneron Research Site
city: Brussels
country: Belgium
facility: Regeneron Research Site
city: Liege
country: Belgium
facility: Regeneron Research Site
city: Loverval
country: Belgium
facility: Regeneron Research Site
city: Brno
country: Czechia
facility: Regeneron Research Site
city: Pardubice
country: Czechia
facility: Regeneron Research Site
city: Praha 1
country: Czechia
facility: Regeneron Research Site
city: Praha
country: Czechia
facility: Regeneron Research Site
city: Bad Bentheim
country: Germany
facility: Regeneron Research Site
city: Berlin
country: Germany
facility: Regeneron Research Site
city: Halle/Saale
country: Germany
facility: Regeneron Research Site
city: Hamburg
country: Germany
facility: Regeneron Research Site
city: Hamburg
country: Germany
facility: Regeneron Research Site
city: Hanau
country: Germany
facility: Regeneron Research Site
city: Leipzig
country: Germany
facility: Regeneron Research Site
city: Lubeck
country: Germany
facility: Regeneron Research Site
city: Mahlow
country: Germany
facility: Regeneron Research Site
city: Munchen
country: Germany
facility: Regeneron Research Site
city: Munster
country: Germany
facility: Regeneron Research Site
city: Quedlinburg
country: Germany
facility: Regeneron Research Site
city: Tuebingen
country: Germany
facility: Regeneron Research Site
city: Witten
country: Germany
facility: Regeneron Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Regeneron Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Regeneron Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Regeneron Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Regeneron Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Regeneron Research Site
city: Incheon
country: Korea, Republic of
facility: Regeneron Research Site
city: Incheon
country: Korea, Republic of
facility: Regeneron Research Site
city: Incheon
country: Korea, Republic of
facility: Regeneron Research Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Research Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Research Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Research Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Research Site
city: Bydgoszcz
country: Poland
facility: Regeneron Research Site
city: Bydgoszcz
country: Poland
facility: Regeneron Research Site
city: Iwonicz Zdroj
country: Poland
facility: Regeneron Research Site
city: Krakow
country: Poland
facility: Regeneron Research Site
city: Lodz
country: Poland
facility: Regeneron Research Site
city: Wroclaw
country: Poland
facility: Regeneron Research Site
city: Barakaldo
country: Spain
facility: Regeneron Research Site
city: Santiago de Compostela
country: Spain
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: