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.

JRCT ID: jRCT2011210011

Registered date:25/05/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Moderate to severe Atopic dermatitis (AD)
• Date of first enrollment: 11/08/2021
• Target sample size: 34
• Countries of recruitment: US,Japan,Canada,Japan,Poland,Japan,Czech,Japan
• Study type: Interventional
• Intervention(s): Adults will subcutaneously receive CC-93538 720mg once a week, 720mg once every 2 weeks, or 360mg once every 2 weeks.

Outcome(s)

Primary Outcome

Change in Eczema Area and Severity Index (EASI%);
Percent change in EASI from Baseline at Week 16

Secondary Outcome

Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) 0 or 1;
Proportion of subjects with an vIGA-AD score of 0 (clear) or 1 (almost clear) and a reduction >= 2 points from Baseline at Week 16
EASI-75;
Proportion of subjects with at least a 75% improvement from Baseline in Eczema Area and Severity Index (EASI-75) at Week 16

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

1. Subject 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). Subjects in Japan must also be of legal age of consent (>= 20 years of age) at the time of signing the ICF.
2. Subject has chronic AD as defined by Hanifin and Rajka that has been present for >= 1 year prior to the baseline visit (Day 1).
3. Subject 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):
a. Body Surface Area (BSA) >= 10%, and
b. EASI score >= 16, and
c. vIGA-AD >= 3, and
d. Pruritus NRS severity score >= 4.
4. Subject 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 (eg, because of important side effects, safety risks, and/or previous intolerance), or has required systemic therapy for control of disease. Inadequate response is defined as either or both of:
a. failure to achieve and/or maintain a disease activity state comparable to IGA 0 [clear] to 2 [mild], despite treatment with a daily regimen of TCS of medium to higher potency (+- TCI as appropriate), applied for at least 4 weeks (28 days) or for the maximum duration recommended by the product prescribing information, whichever was shorter, OR
b. necessity of systemic therapy to control disease.
5. Subject 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. Subject 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. Subjects 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 halflives (whichever is longer) prior to Day 1 and through the treatment duration of the study.
8. Female subjects of childbearing potential must agree to practice a highly effective method of contraception. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly. A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) and must:
a. Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study and through the Final Follow-up Visit. This applies even if the subject practices true abstinence from heterosexual contact.
b. Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, highly effective contraception without interruption throughout the study and for 5 months after the last dose of IP.
Acceptable methods of birth control in this study are the following:
a. combined hormonal (estrogen and progestogen containing) contraception, which may be oral, intravaginal, or transdermal
Note: Intravaginal and transdermal combined hormonal contraception are not approved by Japan Health Authority and would therefore not be acceptable methods contraception for subjects enrolled in this region.
b. progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable.
Note: progestogen-only hormonal contraception is not approved by Japan Health Authority and would therefore not be acceptable methods contraception for subjects enrolled in this region.
c. placement of an intrauterine device (IUD)
d. placement of an intrauterine hormone-releasing system (IUS)
e. bilateral tubal occlusion
f. vasectomized partner
g. sexual abstinence.
9. Subject is willing to receive weekly SC injections throughout the study.
10. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
11. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclude criteria

1. The presence of any of the following will exclude a subject 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 subject-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, subject is receiving, or has received systemic immunosuppressive or immunomodulating drugs (eg, azathioprine, cyclosporine, systemic corticosteroids, interferon gamma (IFN-gamma), Janus kinase inhibitors, methotrexate, mycophenolate-mofetil, etc.) within 4 weeks prior to the Baseline visit.
6. Treatment with immunomodulatory biologics as follows:
a. Dupilumab within 3 months of Baseline visit.
b. Cell-depleting biologics, including to rituximab, within 6 months prior to the Baseline visit.
c. Other immunomodulatory biologics within 5 half-lives (if known) or 16 weeks prior to Baseline visit, whichever is longer.
7. Concurrent treatment with another IP, including through participation in an interventional trial for COVID-19. Prospective subjects may not participate in a concurrent IP study or have received an IP within 5 drug half-lives prior to signing the ICF for this study. Further, for subjects who received an investigational COVID-19 vaccine as part of a clinical trial prior to the first Screening Visit, enrollment must be delayed until the biologic impact of the vaccine is stabilized, as determined by discussion between the Investigator and the Clinical Trial Physician.
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. Administration of any live attenuated vaccine will be prohibited during the study through the Final Follow-up Visit.
9. Previously received CC-93538 treatment (formerly known as RPC4046 and ABT-308).
10. Liver function impairment or persisting elevations of aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT/serum glutamic pyruvic transaminase [SGPT]) that are 2 or more times the upper limit of normal (ULN), or total bilirubin 1.5 times the ULN. Subjects with elevations that are not clinically significant in total bilirubin associated with Gilbert's syndrome may participate.
11. Active chronic or acute skin infection that requires treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to Day 1, or superficial skin infections within 1 week prior to Day 1.
12. Active parasitic/helminthic infection or a suspected parasitic/helminthic infection. Subjects with suspected infections may participate if clinical and/or laboratory assessments rule out active infection prior to randomization.
13. Ongoing infection (including but not limited to, hepatitis B or C, human immunodeficiency virus [HIV], or tuberculosis as defined by standard medical guidelines and testing to rule out is required during screening).
14. A previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 4 weeks prior to screening. Symptoms must have completely resolved and based on Investigator assessment in consultation with the Clinical Trial Physician, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment.
15. Is pregnant or lactating.
16. 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.
17. History of cancer or lymphoproliferative disease, other than a successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma or adequately treated cervical carcinoma in situ, within 5 years of screening.
18. History of alcohol or drug abuse within 5 years prior to initiation of screening.
19. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
20. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
21. Any other condition that confounds the ability to interpret data from the study.

Related Information

• Primary Sponsor: Changliang Zhang
• Secondary ID(s): NCT04800315