A Study to Evaluate Safety and Effectiveness of Cendakimab (CC-93538) in Participants With Moderate to Severe Atopic Dermatitis

Dermatitis, Atopic Clinical Trial

Official title:

A Phase 2, Multicenter, Global, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of Cendakimab (CC-93538) in Adult Subjects With Moderate to Severe Atopic Dermatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04800315
• Other study ID #: CC-93538-AD-001
• Secondary ID: 1111-1260-546220
• Status: Completed
• Phase: Phase 2
• Start date: May 14, 2021
• Est. completion date: November 9, 2022

Study information

• Verified date: December 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effectiveness and safety of 3 dose regimen of CC-93538 in adult participants with moderate to severe Atopic Dermatitis (AD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: November 9, 2022
• Est. primary completion date: July 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Participants must satisfy the following criteria to be enrolled in the study:

1. Participant must be = 18 years and = 75 years of age and have a body weight of = 40 kg (88.2 lb) at the time of signing the informed consent form (ICF).

2. Participant has chronic atopic dermatitis (AD) as defined by Hanifin and Rajka that has been present for = 1 year prior to the baseline visit (Day 1).

3. Participant has moderate to severe, active, and symptomatic AD defined by meeting all of the following criteria on the day of the baseline visit (Day 1):

1. Body Surface Area (BSA) = 10%, and

2. EASI score = 16, and

3. vIGA-AD = 3, and

4. Pruritus Numeric Rating Scale (NRS) severity score = 4.

4. Participant must have a documented history of inadequate response to treatment with topical medications for at least 4 weeks, unless topical treatments are otherwise medically inadvisable or has required systemic therapy for control of disease.

5. Participant must be willing to apply a stable dose of topical emollient (eg, over-the-counter moisturizer, non-medicated emollient, etc.) twice daily for = 7 days prior to the Baseline visit and continue application throughout the study.

6. Participant must commit to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps or other ultraviolet light sources during the study.

7. Participants currently receiving concomitant medications for any reason other than AD, such as inhaled corticosteroids, leukotriene receptor antagonists (eg, montelukast), or mast cell stabilizers (eg, cromolyn sodium) for asthma, must be on a stable regimen, which is defined as not starting a new drug, changing, or stopping dosage within 7 days or 5 half-lives (whichever is longer) prior to Day 1 and through the treatment duration of the study.

8. Female participants of childbearing potential must agree to practice a highly effective method of contraception.

Exclusion Criteria:

1. The presence of any of the following will exclude a participant from enrollment:

Evidence of an active and/or concurrent inflammatory skin condition (eg, seborrheic dermatitis, psoriasis, acute allergic contact dermatitis, etc.) that would interfere with the Investigator or participant-driven evaluations of AD.

2. Evidence of acute AD flare between the Screening and Baseline/ Randomization (eg, doubling of the EASI score between Screening and Baseline).

3. Use of topical treatments that could affect the assessment of AD (eg, corticosteroids, calcineurin inhibitors, tars, antibiotic creams, topical antihistamines) within 7 days of the Day 1 visit.

4. Received phototherapy narrowband UVB (NB-UVB) or broad band phototherapy within 4 weeks prior to the Baseline visit.

5. Evidence of immunosuppression, participant is receiving, or has received systemic immunosuppressive or immunomodulating drugs (eg, azathioprine, cyclosporine, systemic corticosteroids, interferon gamma (IFN-?), Janus kinase inhibitors, methotrexate, mycophenolate-mofetil, etc.) within 4 weeks prior to the Baseline visit.

6. Treatment with immunomodulatory biologics

7. Concurrent treatment with another IP

8. Received a live attenuated vaccine within 1 month prior to the first Screening Visit or anticipates the need to be vaccinated with a live attenuated vaccine during the study.

9. Active parasitic/helminthic infection or a suspected parasitic/helminthic infection.

10. Ongoing infection

11. A history of idiopathic anaphylaxis or a major immunologic reaction (such as anaphylactic reaction, anaphylactoid reaction, or serum sickness) to an immunoglobulin G (IgG) containing agent. A known hypersensitivity to any ingredient in the investigational product (IP) is also exclusionary.

Related Conditions & MeSH terms

• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• CC-93538
Specified dosages on specified days

Other:
• Placebo
Specified dosages on specified days

Locations

Country	Name	City	State
Canada	Institute for Skin Advancement	Calgary	Alberta
Canada	Local Institution - 203	Calgary	Alberta
Canada	Local Institution - 213	Edmonton	Alberta
Canada	Rao Dermatology	Edmonton	Alberta
Canada	Local Institution - 208	Markham	Ontario
Canada	Lynderm Research Inc	Markham	Ontario
Canada	DermEdge	Mississauga	Ontario
Canada	Local Institution - 211	Mississauga	Ontario
Canada	Local Institution - 209	Oakville	Ontario
Canada	The Centre for Clinical Trials Inc.	Oakville	Ontario
Canada	Centre de Recherche Dermatologique du Quebec Metropolitain CRDQ	Quebec
Canada	Local Institution - 202	Quebec
Canada	Dr. Chih-ho Hong Medical Inc.	Surrey	British Columbia
Canada	Enverus Medical Research	Surrey	British Columbia
Canada	Local Institution - 200	Surrey	British Columbia
Canada	Local Institution - 207	Surrey	British Columbia
Canada	Local Institution - 205	Winnipeg	Manitoba
Canada	Wiseman Dermatology Research Inc.	Winnipeg	Manitoba
China	Kawashima Dermatology	Ichikawa
China	Local Institution - 503	Ichikawa
China	Local Institution - 507	Matsudo
China	Miyata Dermatology Clinic	Matsudo
Czechia	Kozni ambulance Kutna Hora	Kutná Hora
Czechia	Local Institution - 407	Kutná Hora
Czechia	Dermamedica	Náchod
Czechia	Local Institution - 403	Náchod
Czechia	CCBR Ostrava	Ostrava
Czechia	Local Institution - 404	Ostrava
Czechia	Center for Clinical and Basic Research Czech Pardubice	Pardubice
Czechia	Local Institution - 405	Pardubice
Czechia	CCBR Czech Prague s.r.o.	Prague
Czechia	Local Institution - 400	Prague
Czechia	Clintrial	Praha
Czechia	Local Institution - 402	Praha
Czechia	FN Motol	Praha 5
Czechia	Local Institution - 401	Praha 5
Czechia	Dermatologicka Ambulance MUDr. Petr Trestik	Svitavy
Czechia	Local Institution - 406	Svitavy
Japan	Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers	Fukuoka
Japan	Local Institution - 504	Fukuoka
Japan	Local Institution - 514	Fukuoka-Shi
Japan	Fukuoka University Hospital	Fukuoka-shi, Fukuoka
Japan	Ichinomiya Municipal Hospital	Ichinomiya
Japan	Local Institution - 506	Ichinomiya
Japan	Local Institution - 511	Itabashi-ku
Japan	Teikyo University Hospital	Itabashi-ku
Japan	Local Institution - 515	Kagoshima
Japan	Saruwatari Dermatology Clinic	Kagoshima
Japan	Local Institution - 513	Kofu
Japan	Yamanashi Prefectual Central Hospital	Kofu
Japan	Local Institution - 505	Kyoto-City
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto-City
Japan	Charme-Clinique	Matsudo
Japan	Local Institution - 510	Matsudo
Japan	Local Institution - 508	Nagoya
Japan	Nagoya City University Hospital	Nagoya
Japan	Local Institution - 512	Obihiro
Japan	Takagi Dermatology	Obihiro
Japan	Local Institution - 517	Osaka
Japan	Nakatsu Hifuka Clinic	Osaka
Japan	Local Institution - 501	Sapporo
Japan	Medical Corporation Kojinkai Housui Sogo Medical Clinic	Sapporo
Japan	Local Institution - 500	Sapporo-shi, Hokkaido
Japan	Sapporo Skin Clinic	Sapporo-shi, Hokkaido
Japan	Local Institution - 502	Shinjuku
Japan	Tokyo Medical University Hospital	Shinjuku
Japan	Local Institution - 509	Yokohoma City, Kanagawa
Japan	Nomura Dermatology Clinic	Yokohoma City, Kanagawa
Poland	Copernicus Podmiot Leczniczy Sp. z o.o.	Gdansk
Poland	Local Institution - 310	Gdansk
Poland	Care Clinic	Katowice
Poland	Centrum Medyczne Angelius Provita	Katowice
Poland	Local Institution - 306	Katowice
Poland	Local Institution - 309	Katowice
Poland	Centrum Medyczne Dermoklinika	Lodz
Poland	Local Institution - 311	Lodz
Poland	Local Institution - 303	Lódz
Poland	Specjalistyczne Gabinety Lekarskie DERMED	Lódz
Poland	Local Institution - 312	Olsztyn
Poland	Miejski Szpital Zespolony w Olsztynie	Olsztyn
Poland	Klinika Zdybski	Ostrowiec Swietokrzyski
Poland	Local Institution - 300	Ostrowiec Swietokrzyski
Poland	Laser Clinic Dermatologia Laserowa Medycyna Estetyczna	Szczecin
Poland	Local Institution - 302	Szczecin
Poland	Local Institution - 308	Szczecin
Poland	Twoja Przychodnia Szczecinskie Centrum Medyczne	Szczecin
Poland	High-Med Przychodnia Specjalistyczna	Warsaw
Poland	Klinika Ambroziak Estederm	Warsaw
Poland	Local Institution - 301	Warsaw
Poland	Local Institution - 307	Warsaw
Poland	Wojskowy Instytut Medyczny	Warsaw
Poland	Centrum Zdrowia WroMedica	Wroclaw
Poland	Kliniczny Szpital Wojewódzki nr 1 im. F. Chopina w Rzeszowie	Wroclaw
Poland	Local Institution - 304	Wroclaw
Poland	Local Institution - 305	Wroclaw
United States	Cahaba Dermatology	Birmingham	Alabama
United States	Clinical Research Center of Alabama	Birmingham	Alabama
United States	Local Institution - 114	Birmingham	Alabama
United States	Local Institution - 119	Birmingham	Alabama
United States	Total Vein and Skin, LLC	Boynton Beach	Florida
United States	Local Institution - 133	Clarkston	Michigan
United States	Skin Research Clarkston/Clarkston Dermatology	Clarkston	Michigan
United States	DS Research	Clarksville	Indiana
United States	Local Institution - 115	Clarksville	Indiana
United States	Local Institution - 106	Delray Beach	Florida
United States	Palm Beach Dermatology Group	Delray Beach	Florida
United States	First OC Dermatology	Fountain Valley	California
United States	Local Institution - 105	Fountain Valley	California
United States	Icahn School of Medicine at Mount Sinai	Great Neck	New York
United States	Local Institution - 130	Great Neck	New York
United States	Local Institution - 112	Hackensack	New Jersey
United States	Skin Laser and Surgery Specialists of New York and New Jersey LLC	Hackensack	New Jersey
United States	Clinical Research Partners LLC	Henrico	Virginia
United States	Burke Pharmaceutical Research	Hot Springs	Arkansas
United States	Local Institution - 129	Hot Springs	Arkansas
United States	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana
United States	Local Institution - 110	Indianapolis	Indiana
United States	Clinical Partners, LLC	Johnston	Rhode Island
United States	Local Institution - 123	Johnston	Rhode Island
United States	JDR Dermatology Research, LLC	Las Vegas	Nevada
United States	Local Institution - 121	Las Vegas	Nevada
United States	DS Research	Louisville	Kentucky
United States	Local Institution - 117	Louisville	Kentucky
United States	International Clinical Research	Murfreesboro	Tennessee
United States	Local Institution - 100	Murfreesboro	Tennessee
United States	Local Institution - 126	New York	New York
United States	Sadick Research Group	New York	New York
United States	Central Sooner Research	Norman	Oklahoma
United States	Local Institution - 111	Norman	Oklahoma
United States	Local Institution - 137	Omaha	Nebraska
United States	Skin Specialists PC	Omaha	Nebraska
United States	Kansas City Dermatology P.A.	Overland Park	Kansas
United States	Local Institution - 116	Overland Park	Kansas
United States	Local Institution - 109	Portland	Oregon
United States	Oregon Medical Research Center, P.C.	Portland	Oregon
United States	Local Institution - 104	Richmond	Virginia
United States	West End Dermatology Associates	Richmond	Virginia
United States	GCP Global Clinical Professionals	Saint Petersburg	Florida
United States	Local Institution - 135	Saint Petersburg	Florida
United States	Aeroallergy Research Labs of Savannah	Savannah	Georgia
United States	Local Institution - 134	Savannah	Georgia
United States	DermAssociates	Silver Spring	Maryland
United States	Local Institution - 125	Silver Spring	Maryland
United States	Local Institution - 108	Springfield	Illinois
United States	Sneeze Wheeze and Itch Associates LLC	Springfield	Illinois
United States	ForCare Clinical Research	Tampa	Florida
United States	Local Institution - 101	Tampa	Florida
United States	Local Institution - 127	Tulsa	Oklahoma
United States	Vital Prospects Clinical Research Institute PC - CRN - PPDS	Tulsa	Oklahoma
United States	George Washington University School of Medicine and Health Sciences	Washington	District of Columbia
United States	Local Institution - 128	Washington	District of Columbia
United States	Local Institution - 107	West Lafayette	Indiana
United States	Randall Dermatology	West Lafayette	Indiana
United States	Local Institution - 103	West Palm Beach	Florida
United States	Metabolic Research Institute Inc	West Palm Beach	Florida
United States	Local Institution - 138	Westfield	Indiana
United States	Randall Dermatology - Westfield Campus	Westfield	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada,  China,  Czechia,  Japan,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Percentage Change From Baseline in EASI at Week 16	The Eczema Area and Severity Index (EASI) is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with Atopic Dermatitis (AD) and the intensity of each of 4 main signs of AD (eg, erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The sum of the scores is totaled (0 to 72), the lower the score the better.	From initial EASI measurement to week 16
Secondary	Percentage of Responders With an vIGA-AD Score of 0 (Clear) or 1 (Almost Clear) and a Reduction = 2 Points From Baseline at Week 16	The Validated Investigator Global Assessment (vIGA-AD) is a validated 5-point assessment intended to assess the global severities of key acute clinical signs of AD, including erythema, induration/papulation, oozing/crusting (lichenification excluded). The rating of clear (0), almost clear (1), mild (2), moderate (3) and severe (4), will be assessed at scheduled visits. The vIGA-AD must be conducted before the EASI assessment. The vIGA-AD is a static evaluation conducted without regard to the score obtained at a previous visit.; Percentage of responders calculated using Multiple Imputation (MI) approach.; For participants discontinued study drug, whose vIGA-AD response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR).	From initial vIGA-AD assessment to week 16
Secondary	Percentage of EASI-75 Responders at Week 16	The EASI is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with AD and the intensity of each of 4 main signs of AD (eg, erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The sum of the scores is totaled (0 to 72), the lower the score the better.; Percentage of responders calculated using Multiple Imputation (MI) approach.; For participants discontinued study drug, whose EASI-75 response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR).	From initial EASI measurement to week 16
Secondary	Percentage of EASI-90 Responders at Week 16	The Eczema Area and Severity Index (EASI) is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with Atopic Dermatitis (AD) and the intensity of each of 4 main signs of AD (eg, erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The sum of the scores is totaled (0 to 72), the lower the score the better.; Percentage of responders calculated using Multiple Imputation (MI) approach.; For participants discontinued study drug, whose EASI-90 response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR).	From initial EASI measurement to week 16
Secondary	Percent Change in Mean SCORAD Scores From Baseline at Week 16	The SCORAD is a validated scoring index for atopic dermatitis, which combines extent (0 to 100), severity (0 to 18), and subjective symptoms (0 to 20) based on pruritus and sleep loss, each scored (0 to 10). The subject will assess the subjective symptoms (itch and sleepless) part of the assessment.; SCORing Atopic Dermatitis Index (SCORAD) score ranges from 0 to 103, higher scores indicate more severe disease.	From initial SCORAD measurement to week 16
Secondary	Percent Change From Baseline in Pruritus NRS at Week 16	Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is indicated by a = 2 to 4-point change from baseline in Peak Pruritus NRS score. The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point NRS, ranging from 0 ("no pruritus") to 10 ("the worst pruritus imaginable").	From initial NRS measurement to week 16
Secondary	Percentage of Participants With a Response and Pruritus NRS Change of = 4 Points From Baseline at Week 16	Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is indicated by a = 2 to 4-point change from baseline in Peak Pruritus NRS score. The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point NRS, ranging from 0 ("no pruritus") to 10 ("the worst pruritus imaginable").; Percentage of responders calculated using Multiple Imputation (MI) approach.; For participants discontinued study drug, whose pruritus NRS response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR).	From initial NRS assessment to week 16
Secondary	Time to Achieve at Least 4 Points of Improvement in the Severity of Pruritus NRS Scale.	Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is indicated by a = 2 to 4-point change from baseline in Peak Pruritus NRS score. The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point NRS, ranging from 0 ("no pruritus") to 10 ("the worst pruritus imaginable").	From initial NRS pruritus response up to study day 127 (127 days)
Secondary	Adjust Mean Percentage Change in BSA in Atopic Dermatitis From Baseline at Week 16	Body Surface Area involvement will be calculated from the sum of the number of handprints of skin afflicted with atopic dermatitis in a body region. The number of handprints of skin afflicted with atopic dermatitis in a body region can be used to determine the extent (%) to which a body region is involved with AD. When measuring, the handprint unit refers to the size of each individual subject's hand with fingers in a closed position. BSA will be calculated by the Investigator or qualified designee using the 1% handprint rule, in which the area represented by the palm with all 5 digits adducted together is approximately 1% of the subject's BSA.	From initial BSA assessment to week 16
Secondary	Number of Participants With Treatment Emergent Adverse Events	Treatment emergent adverse events	From first treatment to the end of follow up, approximately 32 weeks
Secondary	Number of Participants With the Presence of Serum Antibodies to CC-93538		From first treatment to the end of follow up, approximately 32 weeks
Secondary	Serum Trough Concentration at Week 16	A serum trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered. Serum trough concentrations (Ctrough) of CC-93538 will be summarized with descriptive statistics by treatment and visit.	At week 16
Secondary	Number of Participants With Clinically Significant Laboratory Abnormalities		From first treatment to the end of follow up, approximately 32 weeks

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