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

Phase 2

Completed

• Conditions: Dermatitis, Atopic; Eczema
• Interventions: Drug: CC-93538; Other: Placebo

• Registration Number: NCT04800315
• Lead Sponsor: Celgene

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-03-12
• Study First Submitted QC: 2021-03-12
• Study First Posted: 2021-03-16
• Study Start: 2021-05-14
• Primary Completion: 2022-07-20
• Study Completion: 2022-11-09
• Disposition First Submitted: 2023-07-14
• Results First Submitted: 2023-11-08
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-14
• Last Update Submitted: 2023-12-14
• Results First Posted: 2024-01-03
• Disposition First Posted: 2024-01-03
• Last Update Posted: 2024-01-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 221

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-γ), 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose 2: CC-93538 SC Q2W and Placebo alternating every other week SC Q2W	Placebo	Starting at the baseline visit, active IP will be administered. On the alternate weeks, placebo will be administered to maintain the blind.
Dose 3: CC-93538 SC Q2W and Placebo SC weekly	CC-93538	Starting at the baseline visit, active IP and matching placebo will be administered. On the alternate weeks, placebo will be administered weekly to maintain the blind.
Dose 3: CC-93538 SC Q2W and Placebo SC weekly	Placebo	Starting at the baseline visit, active IP and matching placebo will be administered. On the alternate weeks, placebo will be administered weekly to maintain the blind.
Placebo SC QW	Placebo	Administration of placebo each week.
Dose 2: CC-93538 SC Q2W and Placebo alternating every other week SC Q2W	CC-93538	Starting at the baseline visit, active IP will be administered. On the alternate weeks, placebo will be administered to maintain the blind.
Dose 1: CC-93538 SC QW	CC-93538	Administration of CC-93538 Subcutaneous (SC) Once weekly (QW) for 16 weeks.

Primary Outcome Measures

Name	Time	Method
Mean Percentage Change From Baseline in EASI at Week 16	From initial EASI measurement to 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.

Secondary Outcome Measures

Name	Time	Method
Percentage of EASI-90 Responders at Week 16	From initial EASI measurement to 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).
Time to Achieve at Least 4 Points of Improvement in the Severity of Pruritus NRS Scale.	From initial NRS pruritus response up to study day 127 (127 days)	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").
Percent Change From Baseline in Pruritus NRS at Week 16	From initial NRS measurement to 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").
Number of Participants With Treatment Emergent Adverse Events	From first treatment to the end of follow up, approximately 32 weeks	Treatment emergent adverse events
Number of Participants With the Presence of Serum Antibodies to CC-93538	From first treatment to the end of follow up, approximately 32 weeks
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	From initial vIGA-AD assessment to 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).
Percent Change in Mean SCORAD Scores From Baseline at Week 16	From initial SCORAD measurement to 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.
Percentage of EASI-75 Responders at Week 16	From initial EASI measurement to 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).
Percentage of Participants With a Response and Pruritus NRS Change of ≥ 4 Points From Baseline at Week 16	From initial NRS assessment to 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).
Serum Trough Concentration at Week 16	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.
Adjust Mean Percentage Change in BSA in Atopic Dermatitis From Baseline at Week 16	From initial BSA assessment to 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.
Number of Participants With Clinically Significant Laboratory Abnormalities	From first treatment to the end of follow up, approximately 32 weeks

Trial Locations

Locations (156)

Clinical Research Center of Alabama; 🇺🇸 Birmingham, Alabama, United States

Local Institution - 119; 🇺🇸 Birmingham, Alabama, United States

Cahaba Dermatology; 🇺🇸 Birmingham, Alabama, United States

Local Institution - 114; 🇺🇸 Birmingham, Alabama, United States

Burke Pharmaceutical Research; 🇺🇸 Hot Springs, Arkansas, United States

Local Institution - 129; 🇺🇸 Hot Springs, Arkansas, United States

First OC Dermatology; 🇺🇸 Fountain Valley, California, United States

Local Institution - 105; 🇺🇸 Fountain Valley, California, 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

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