Efficacy and Safety of REGN3500 Monotherapy and Combination of REGN3500 Plus Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis

NCT03736967 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: R3500-AD-17982018-001543-30
• Study Type: interventional
• Target: 206
• Locations: 7 countries
• Sites: 66

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

Conditions

Atopic Dermatitis

Keywords

Moderate; Severe

Outcome Measures

Primary Outcomes (1)

• 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

  The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, induration, 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. Percent change from baseline in EASI score at Week 16 based on observed values set to missing after rescue treatment was reported. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.

  Week 16

Secondary Outcomes (25)

• Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on All Observed Values Regardless of Rescue Treatment at Week 16

  Week 16

• 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

  Week 16

• 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

  Week 16

• 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

  Week 16

• 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

  Week 16

Study Arms (4)

REGN3500

EXPERIMENTAL

Drug: REGN3500

Dupilumab

EXPERIMENTAL

Drug: Dupilumab

Combo

EXPERIMENTAL

Drug: REGN3500 + Dupilumab Combo

Placebo

EXPERIMENTAL

Drug: REGN3500; Drug: Dupilumab; Drug: Placebo

Interventions

REGN3500 DRUG

Administered subcutaneous (SC) every 2 weeks (q2w)

Placebo; REGN3500

Dupilumab DRUG

Administered SC q2w

Also known as: REGN668, Dupixent

Dupilumab; Placebo

REGN3500 + Dupilumab Combo DRUG

Administered SC q2w

Also known as: REGN668, Dupixent

Combo

Placebo DRUG

Administered SC q2w

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Eczema Area and Severity Index (EASI) score ≥16 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 topical AD medication(s) or for whom topical treatments are medically inadvisable

You may not qualify if:

• 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
• 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
• 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
• History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening
• Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (HCV Ab) at the screening visit
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (66)

Regeneron Research Site

Phoenix, Arizona, 85259, United States

Location

Regeneron Research Site

Fountain Valley, California, 92708, United States

Location

Regeneron Research Site

Long Beach, California, 90808, United States

Location

Regeneron Research Site

Los Angeles, California, 90025, United States

Location

Regeneron Research Site

Los Angeles, California, 90033, United States

Location

Regeneron Research Site

Sacramento, California, 95815, United States

Location

Regeneron Research Site

Davie, Florida, 33328, United States

Location

Regeneron Research Site

Sandy Springs, Georgia, 30328, United States

Location

Regeneron Research Site

Rockville, Maryland, 20850, United States

Location

Regeneron Research Site

Bay City, Michigan, 48706, United States

Location

Regeneron Research Site

Saint Joseph, Michigan, 49085, United States

Location

Regeneron Research Site

Troy, Michigan, 48084, United States

Location

Regeneron Research Site

Forest Hills, New York, 11375, United States

Location

Regeneron Research Site

New York, New York, 10022, United States

Location

Regeneron Research Site

New York, New York, 10029, United States

Location

Regeneron Research Site

The Bronx, New York, 10467, United States

Location

Regeneron Research Site

High Point, North Carolina, 27262, United States

Location

Regeneron Research Site

Norman, Oklahoma, 73071, United States

Location

Regeneron Research Site

Portland, Oregon, 97239, United States

Location

Regeneron Research Site

Pittsburgh, Pennsylvania, 15213, United States

Location

Regeneron Research Site

Arlington, Texas, 76014, United States

Location

Regeneron Research Site

Richmond, Virginia, 23220, United States

Location

Regeneron Research Site

Anderlecht, 1070, Belgium

Location

Regeneron Research Site

Antwerp, 2650, Belgium

Location

Regeneron Research Site

Brussels, 1090, Belgium

Location

Regeneron Research Site

Brussels, 1200, Belgium

Location

Regeneron Research Site

Liège, 4000, Belgium

Location

Regeneron Research Site

Loverval, 6280, Belgium

Location

Regeneron Research Site

Brno, 602 00, Czechia

Location

Regeneron Research Site

Pardubice, 530 02, Czechia

Location

Regeneron Research Site

Prague, 110 00, Czechia

Location

Regeneron Research Site

Prague, 130 00, Czechia

Location

Regeneron Research Site

Bad Bentheim, 48455, Germany

Location

Regeneron Research Site

Berlin, 12459, Germany

Location

Regeneron Research Site

Halle, 06120, Germany

Location

Regeneron Research Site

Hamburg, 20537, Germany

Location

Regeneron Research Site

Hamburg, 22391, Germany

Location

Regeneron Research Site

Hanau, 63450, Germany

Location

Regeneron Research Site

Leipzig, 04103, Germany

Location

Regeneron Research Site

Lübeck, 23538, Germany

Location

Regeneron Research Site

Mahlow, 15831, Germany

Location

Regeneron Research Site

München, 80337, Germany

Location

Regeneron Research Site

Münster, 48149, Germany

Location

Regeneron Research Site

Quedlinburg, 06484, Germany

Location

Regeneron Research Site

Tübingen, 72076, Germany

Location

Regeneron Research Site

Witten, 58453, Germany

Location

Regeneron Research Site

Bydgoszcz, 85-065, Poland

Location

Regeneron Research Site

Bydgoszcz, 85-796, Poland

Location

Regeneron Research Site

Iwonicz-Zdrój, 38-440, Poland

Location

Regeneron Research Site

Krakow, 30-033, Poland

Location

Regeneron Research Site

Lodz, 90-436, Poland

Location

Regeneron Research Site

Wroclaw, 51-685, Poland

Location

Regeneron Research Site

Gyeonggi-do, 13496, South Korea

Location

Regeneron Research Site

Gyeonggi-do, 13620, South Korea

Location

Regeneron Research Site

Gyeonggi-do, 14584, South Korea

Location

Regeneron Research Site

Gyeonggi-do, 16499, South Korea

Location

Regeneron Research Site

Gyeonggi-do, 18450, South Korea

Location

Regeneron Research Site

Incheon, 21431, South Korea

Location

Regeneron Research Site

Incheon, 21565, South Korea

Location

Regeneron Research Site

Incheon, 22332, South Korea

Location

Regeneron Research Site

Seoul, 03080, South Korea

Location

Regeneron Research Site

Seoul, 03722, South Korea

Location

Regeneron Research Site

Seoul, 06591, South Korea

Location

Regeneron Research Site

Seoul, 07441, South Korea

Location

Regeneron Research Site

Barakaldo, 48903, Spain

Location

Regeneron Research Site

Santiago de Compostela, 15706, Spain

Location

MeSH Terms

Conditions

Dermatitis, Atopic; Lymphoma, Follicular

Interventions

itepekimab; dupilumab

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Limitations and Caveats

The decision was made by the sponsor to terminate the study on 12 Feb 2020 due to lack of efficacy. Study enrollment was not complete at that time, therefore planned sample sizes were not met. Participants discontinued study drug and transitioned into the post-treatment follow-up period. As a result of the decision to terminate the study, all statistical analyses were descriptive and no hypothesis testing was performed.

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 9, 2018
• Study Start: November 12, 2018
• Primary Completion: March 13, 2020
• Study Completion: July 28, 2020
• Last Updated: November 1, 2021
• Results First Posted: November 1, 2021

Record last verified: 2021-10

Locations

CZ (4); KR (12); PL (6); BE (6); ES (2); DE (14); US (22)