Clinical trial NCT03738423: Efficacy, Safety, and Pharmacokinetic Profiles of REGN3500 Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis
Official title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study Investigating the Efficacy, Safety, and Pharmacokinetic Profiles of REGN3500 Administered to 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: 2018-11-13
Enrollment: 129
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 assess the efficacy of REGN3500 monotherapy in Atopic dermatitis (AD), as well as understand the dose-response relationship, compared with placebo treatment, in adult patients with moderate-to-severe AD.

Secondary objectives are to:

* Assess the safety and tolerability of subcutaneous (SC) doses of REGN3500 monotherapy in adult patients with moderate-to-severe AD
* Assess the Pharmacokinetics (PK) of REGN3500 in adult patients with moderate-to-severe AD
* Assess the immunogenicity of REGN3500 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. IGA score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at screening and baseline visits
4. ≥10% Body surface area (BSA) of AD involvement at the screening and baseline visits
5. 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. Participation in a prior anti-Interleukin (IL)-33 medication clinical study
2. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the baseline visit
3. Having used any of the following treatments within 4 weeks before the baseline visit or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment:

   1. Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, Interferon-gamma (IFN-γ), Janus kinase inhibitors, azathioprine, methotrexate, etc)
   2. Phototherapy for AD
4. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the baseline visit
5. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
6. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit
7. Known or suspected history of immunosuppression
8. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening
9. Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (HCV Ab) at the screening visit
10. 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
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
Secondary outcomes:
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) (Greater Than or Equal to [≥] 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 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 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 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 Score ≥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 Daily Peak Pruritus NRS Score ≥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) up to Week 16
timeFrame: Up to week 16
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) up to Week 36
timeFrame: 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: Number of Participants With Positive Treatment-Emergent Anti-REGN3500 Antibodies (ADA)
timeFrame: Up to week 36
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Regeneron Study Site
state: Alabama
city: Phoenix
country: United States
facility: Regeneron Study Site
state: Arizona
city: Scottsdale
country: United States
facility: Regeneron Study Site
state: Arizona
city: Tucson
country: United States
facility: Regeneron Study Site
state: Arizona
city: Little Rock
country: United States
facility: Regeneron Study Site
state: Arkansas
city: Fountain Valley
country: United States
facility: Regeneron Study Site
state: California
city: Fremont
country: United States
facility: Regeneron Study Site
state: California
city: Oceanside
country: United States
facility: Regeneron Study Site
state: California
city: Sacramento
country: United States
facility: Regeneron Study Site
state: California
city: Santa Monica
country: United States
facility: Regeneron Study Site
state: California
city: Jacksonville
country: United States
facility: Regeneron Study Site
state: Florida
city: Macon
country: United States
facility: Regeneron Study Site
state: Georgia
city: Skokie
country: United States
facility: Regeneron Study Site
state: Illinois
city: Evansville
country: United States
facility: Regeneron Study Site
state: Indiana
city: Overland Park
country: United States
facility: Regeneron Study Site
state: Kansas
city: Louisville
country: United States
facility: Regeneron Study Site
state: Kentucky
city: Louisville
country: United States
facility: Regeneron Study Site
state: Kentucky
city: Louisville
country: United States
facility: Regeneron Study Site
state: Kentucky
city: Saint Joseph
country: United States
facility: Regeneron Study Site
state: Michigan
city: Minneapolis
country: United States
facility: Regeneron Study Site
state: Minnesota
city: Las Vegas
country: United States
facility: Regeneron Study Site
state: Nevada
city: Lebanon
country: United States
facility: Regeneron Study Site
state: New Hampshire
city: New York
country: United States
facility: Regeneron Study Site
state: New York
city: Wilmington
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Cincinnati
country: United States
facility: Regeneron Study Site
state: Ohio
city: Norman
country: United States
facility: Regeneron Study Site
state: Oklahoma
city: North Charleston
country: United States
facility: Regeneron Study Site
state: South Carolina
city: San Antonio
country: United States
facility: Regeneron Study Site
state: Texas
city: San Antonio
country: United States
facility: Regeneron Study Site
state: Texas
city: San Antonio
country: United States
facility: Regeneron Study Site
state: Texas
city: Norfolk
country: United States
facility: Regeneron Study Site
state: Virginia
city: Kogarah
country: Australia
facility: Regeneron Study Site
city: Melbourne
country: Australia
facility: Regeneron Study Site
city: Calgary
country: Canada
facility: Regeneron Study Site
state: Alberta
city: Hamilton
country: Canada
facility: Regeneron Study Site
state: Ontario
city: Hamilton
country: Canada
facility: Regeneron Study Site
state: Ontario
city: Toronto
country: Canada
facility: Regeneron Study Site
state: Ontario
city: Windsor
country: Canada
facility: Regeneron Study Site
state: Ontario
city: Verdun
country: Canada
facility: Regeneron Study Site
state: Quebec
city: Brno
country: Czechia
facility: Regeneron Study Site
city: Nachod
country: Czechia
facility: Regeneron Study Site
city: Ostrava
country: Czechia
facility: Regeneron Study Site
city: Praha
country: Czechia
facility: Regeneron Study Site
city: Bad Bentheim
country: Germany
facility: Regeneron Study Site
city: Berlin
country: Germany
facility: Regeneron Study Site
city: Berlin
country: Germany
facility: Regeneron Study Site
city: Frankfurt
country: Germany
facility: Regeneron Study Site
city: Hamburg
country: Germany
facility: Regeneron Study Site
city: Hanau
country: Germany
facility: Regeneron Study Site
city: Ibbenburen
country: Germany
facility: Regeneron Study Site
city: Leipzig
country: Germany
facility: Regeneron Study Site
city: Lubeck
country: Germany
facility: Regeneron Study Site
city: Munchen
country: Germany
facility: Regeneron Study Site
city: Munster
country: Germany
facility: Regeneron Study Site
city: Tubingen
country: Germany
facility: Regeneron Study Site
city: Tuebingen
country: Germany
facility: Regeneron Study Site
city: Witten
country: Germany
facility: Regeneron Study Site
city: Oroshaza
country: Hungary
facility: Regeneron Study Site
state: Bekes
city: Debrecen
country: Hungary
facility: Regeneron Study Site
state: Hajdu-Bihar
city: Budapest
country: Hungary
facility: Regeneron Study Site
city: Chuo
country: Japan
facility: Regeneron Study Site
city: Hiroshima
country: Japan
facility: Regeneron Study Site
city: Kanagawa
country: Japan
facility: Regeneron Study Site
city: Kyoto
country: Japan
facility: Regeneron Study Site
city: Kyoto
country: Japan
facility: Regeneron Study Site
city: Shizuoka
country: Japan
facility: Regeneron Study Site
city: Shizuoka
country: Japan
facility: Regeneron Study Site
city: Wakayama
country: Japan
facility: Regeneron Study Site
city: Yamanashi
country: Japan
facility: Regeneron Study Site
city: Bucheon-Si
country: Korea, Republic of
facility: Regeneron Study Site
city: Busan
country: Korea, Republic of
facility: Regeneron Study Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Regeneron Study Site
city: Incheon
country: Korea, Republic of
facility: Regeneron Study Site
city: Incheon
country: Korea, Republic of
facility: Regeneron Study Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Study Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Study Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Study Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Study Site
city: Krakow
country: Poland
facility: Regeneron Study Site
city: Lodz
country: Poland
facility: Regeneron Study Site
city: Szczecin
country: Poland
facility: Regeneron Study Site
city: Warszawa
country: Poland
facility: Regeneron Study Site
city: Warszawa
country: Poland
facility: Regeneron Study Site
city: Wroclaw
country: Poland
facility: Regeneron Study Site
city: Wroclaw
country: Poland
facility: Regeneron Study Site
city: Barakaldo
country: Spain
facility: Regeneron Study Site
city: Cordoba
country: Spain
facility: Regeneron Study Site
city: Madrid
country: Spain
facility: Regeneron Study Site
city: Santiago de Compostela
country: Spain
facility: Regeneron Study Site
city: Sheffield
country: United Kingdom
facility: Regeneron Study Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: