atopic dermatitis chronic skin inflammation
Conditions
Interventions
Nemolizumab (CD14152) or placebo will be provided as lyophilized powder in a
dual-chamber syringe (DCS) for solution for injection.
During the initial treatment period, eligible subjects will be ra
group 1B will receive an injection
of nemolizumab Q8W, with alternating placebo Q8W (last active injection at Week
40 and last placebo injection at Week 44)
and group 1C will receive placebo
Q4W. Subjects in group 2 who are clinical responders will continue to receive
placebo Q4W.
Patients will additionally use moisturizer daily, will be provided with
Sponsors
Galderma
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged >= 12 years at the screening visit. Note: Enrollment of subjects aged 12 to 17 years has been opened after the IDMC has assessed interim safety data from the phase 2 study (Protocol 116912) and provided recommendations to the sponsor, who then determined the eligibility of this age group for enrollment in the study. The sponsor sent a written communication to the site confirming that the study is open for enrollment of adolescents. Adolescents could not be enrolled in the study until such communication was received. 2. Chronic atopic dermatitis (AD) for at least 2 years before the screening visit, and confirmed according to American Academy of Dermatology Consensus Criteria at the time of the screening visit. 3. EASI score >= 16 at both the screening and baseline visits. 4. IGA score >= 3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) at both the screening and baseline visits. 5. AD involvement >= 10% of body surface area (BSA) at both the screening and baseline visits. 6. Peak (maximum) pruritus NRS score of at least 4.0 at the screening and baseline visit. 7. Documented recent history (within 6 months before the screening visit) of inadequate response to topical medications (TCS with or without TCI). 8. Agree to apply a moisturizer throughout the study from the screening visit; agree to apply authorized topical therapy from the screening visit and throughout the study as determined appropriate by the investigator. 9. Female subjects of childbearing potential (ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile) must agree either to commit to true abstinence throughout the study and for 12 weeks after the last study drug injection, when this is in line with the preferred and usual lifestyle of the subject, or to use an adequate and approved method of contraception throughout the study and for 12 weeks after the last study drug injection. This criterion also applies to a prepubertal female subject who begins menses during the study. *In Germany only, if a subject has reached Tanner stage 3 breast development, even if not having menarche, the subject will be considered a female of childbearing potential. Adequate and approved methods of contraception applicable for the subject and/or her partner are defined below: - Progestogen-only oral hormonal contraception; - Combination of male condom with cap, diaphragm, or sponge with spermicide (double barrier methods) (*In Germany only, double barrier methods are not considered a highly effective method of contraception); Note: *Double barrier methods* refers to simultaneous use of a physical barrier by each partner. Use of a single barrier method (eg, condom) together with a spermicide is not acceptable. - Combined (estrogen- and progestogen-containing) oral, intravaginal, or transdermal hormonal contraception; - Injectable or implanted hormonal contraception; - Intrauterine devices or intrauterine hormone-releasing system; - Bilateral tubal ligation or tube insert (such as the Essure system) at least 3 months before the study; - Bilateral vasectomy of partner at least 3 months before the study 10. Female subjects of non-childbearing potential must meet one of the following criteria: •Absence of menstrual bleed
Exclusion criteria
Exclusion criteria: 1. Body weight 2 days per week, nighttime awakenings > 2 or more times per week, or some interference with normal activities) during the preceding 3 months. 2c. Asthma Control Test <= 19 (only for subjects with a history of asthma). 2d. Peak expiratory flow < 80% of the predicted value. 3. Subjects with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis. 4. Cutaneous infection within 1 week before the baseline visit, any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics or antifungals within 2 weeks before the baseline visit, or any confirmed or suspected coronavirus disease (COVID)-19 infection within 2 weeks before the screening or baseline visit. Subjects may be rescreened once the infection has resolved. Resolution of COVID-19 infection can be confirmed by recovery assessment methods, as described in Section 8.3.4.2; Note: Subjects with chronic, stable use of prophylactic treatment for recurrent herpes viral infection can be included in this study. 5. Requiring rescue therapy for atopic dermatitis (AD) during the run-in period or expected to require rescue therapy within 2 weeks following the baseline visit. 6. Positive serology results (hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb], hepatitis C antibody, or human immunodeficiency virus antibody) at the screening visit. 7. Having received any of the treatments specified in Table 6 reported in the protocol within the specified timeframe before the baseline visit. 8. Previous treatment with Nemolizumab. 9. Subjects who, after a full treatment course of 16 weeks with dupilumab, experienced worsening of their AD or failed to achieve minimal improvement (eg, <= 10% reduction in EASI or no reduction in IGA) 10. Pregnant women (positive serum pregnancy test result at the screening visit or positive urine pregnancy test at the baseline visit), breastfeeding women, or women planning a pregnancy during the clinical study. 11. History of lymphoproliferative disease or history of malignancy of any organ system within the last 5 years, except for (1) basal cell carcinoma, squamous cell carcinoma in situ (Bowen's disease), or carcinomas in situ of the cervix that have been treated and have no evidence of recurrence in the last 12 weeks before the baseline visit, or (2) actinic keratoses that have been treated. 12. History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody) or to any of the study drug excipients. 13. History of intolerance to TCS or for whom TCS is not advisable (eg, hypersensitivity, significant skin atrophy). 14. Known active or untreated latent tuberculosis infection. Note: Subjects who have a documented history of completion of an appropriate TB treatment regimen for active or latent TB with no history of re-exposure to TB since their treatment was completed are eligible to participate in the study. 15. Known or suspected immunosuppression or u
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Co-Primary Endpoints: • Proportion of subjects with an IGA success (defined as an IGA of 0 [clear] or 1 [almost clear] and a >= 2-point reduction from baseline) at Week 16 • Proportion of subjects with EASI-75 (>= 75% improvement in EASI from baseline) at Week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary Endpoints: • Proportion of subjects with an improvement of PP NRS >= 4 at Week 16 • Proportion of subjects with PP NRS = 4 at Week 16 • Proportion of subjects with an improvement of PP NRS >= 4 at Week 4 • Proportion of subjects with PP NRS = 4 at Week 2 • Proportion of subjects with an improvement of PP NRS >= 4 at Week 1 • Proportion of subjects with EASI-75 and improvement of PP NRS >= 4 at Week 16 • Proportion of subjects with IGA success and improvement of PP NRS >= 4 at Week 16 Both primary and key secondary endpoints will be evaluated for the following populations: • Baseline PP NRS >= 4 (full population) • Baseline PP NRS >= 7 For further secondary endpoints, safety endpoints and other endpoints please refer to sections 7.5 to 7.7 of the protocol. | — |
Countries
Netherlands
Outcome results
None listed