E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess the efficacy and safety of Nemolizumab (CD14152) after a 16-week treatment period in adult and adolescent subjects with moderate-to-severe atopic dermatitis not adequately controlled with topical treatments. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy and safety of maintenance treatment with Nemolizumab (CD14152) for up to an additional 32 weeks. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional Subject Interviews, optional standardized clinical photographs of AD lesions and Pharmacogenomic testing |
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E.3 | Principal 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. The sponsor will send a written communication to the site confirming that the study is open for enrollment of adolescents. Adolescents must not be enrolled in the study until such communication is received. 2. Chronic 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); - 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 bleeding for 1 year prior to screening without any other medical reason, confirmed with follicle-stimulating hormone (FSH) level in the postmenopausal range; •Documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months before screening. 11. Subject (and guardian, when applicable) willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol, including daily diary recordings by the subject using an electronic handheld device provided for this study. 12. Understand and sign an informed consent form (and assent form, when applicable) before any investigational procedure(s) are performed. |
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E.4 | Principal exclusion criteria |
1. Body weight < 30 kg. 2. Subjects meeting 1 or more of the following criteria at screening or baseline: 2a. Had an exacerbation of asthma requiring hospitalization in the preceding 12 months. 2b. Reporting asthma that has not been well-controlled (ie, symptoms occurring on > 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 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 (TB) 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 unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment. 16. Presence of confounding skin condition that may interfere with study assessments (eg, Netherton syndrome, psoriasis, cutaneous T-cell lymphoma [mycosis fungoides or Sezary syndrome], contact dermatitis, chronic actinic dermatitis, dermatitis herpetiformis). 17. Any medical or psychological condition or any clinically relevant laboratory abnormalities, such as but not limited to elevated ALT or AST (> 3 × upper limit of normal [ULN]) in combination with elevated bilirubin (> 2 × ULN), during the screening period that may put the subject at significant risk according to the investigator’s judgment, if he/she participates in the clinical study, or may interfere with study assessments (eg, poor venous access or needle-phobia). 18. Planned or expected major surgical procedure during the clinical study. 19. Subjects unwilling to refrain from using prohibited medications during the clinical study. 20. Currently participating or participated in any other study of a drug or device, within the past 8 weeks before the screening visit, (or 5 half-lives of the investigational drug, whichever is longer), or is in an exclusion period (if verifiable) from a previous study. 21.History of alcohol or substance abuse within 6 months of the screening visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key Secondary Endpoints: • Proportion of subjects with an improvement of PP NRS ≥ 4 at Week 16 • Proportion of subjects with PP NRS < 2 at Week 16 • Proportion of subjects with an improvement of sleep disturbance NRS (SD NRS) ≥ 4 at Week 16 • Proportion of subjects with an improvement of PP NRS ≥ 4 at Week 4 • Proportion of subjects with PP NRS < 2 at Week 4 • Proportion of subjects with an improvement of 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As specified within the list of endpoints |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, Quality of Life |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Korea, Republic of |
New Zealand |
United States |
Austria |
Latvia |
Lithuania |
Poland |
Netherlands |
Spain |
Czechia |
Germany |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 10 |