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 long-term safety of Nemolizumab (CD14152) in adult and adolescent subjects with moderate-to-severe atopic dermatitis (AD). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the long-term efficacy of Nemolizumab (CD14152) in adult and adolescent subjects with moderate-to-severe AD |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who may benefit from study participation in the opinion of the investigator and had participated in a prior nemolizumab study for AD including:
a. Subjects who completed the initial treatment period (Week 16 visit) in a Phase 3 pivotal study (SPR.118161 or SPR.118169) and do not qualify for the maintenance period;
OR
b. Subjects who completed the maintenance period (Week 48 visit) in a Phase 3 pivotal study (SPR.118161 or SPR.118169);
OR
c. Subjects who completed the treatment period (Week 16 visit) in the Phase 2 vaccination safety study (SPR.118380);
OR
d. Subjects who completed the treatment period (Week 16 visit) in the Phase 2 adolescent PK/safety study (SPR.116912);
OR
e. Subjects who completed the treatment period (Week 24 visit) in the Phase 2b dose-ranging study (SPR.114322) and remain insufficiently controlled on topical therapy alone;
OR
f. Subjects who discontinued study medication in a prior study and completed required study visits prior to LTE participation (Week 16 visit for SPR.118161 and SPR.118169 initial treatment period, Week 32 visit for SPR.118161 and SPR.118169 maintenance period; final study visits for SPR.118380 [Week 16], SPR.116912 [Week 16], and SPR.114322 [Week 24]), unless the subject experienced an AE that may present an unreasonable risk if study medication is continued;
Note(s): For ongoing studies, transfer into the LTE study should occur as soon as possible to minimize gaps in study medication dosing. Subjects who satisfy inclusion criteria 1a through 1c are permitted to enroll immediately into the LTE study, provided other eligibility criteria are met.
Subjects satisfying inclusion criterion 1d can be considered for eligibility after interim PK and safety analyses of data from SPR.116912 are conducted by the sponsor and an IDMC to determine whether enrollment of the adolescent age group (12-17 years) is safe. Following Independent Ethics Committees/Institutional Review Boards approval, the sponsor will send
a written communication to the site confirming that the study is open for enrollment of adolescents. Adolescents and/or subjects from SPR.116912 even if presently 18 years of age must not be enrolled in the study until such communication is received. Subjects who enroll within 28 days of completing the final visit of a lead-in study may use final study assessments for
the screening visit, unless the subject prematurely discontinued study drug in the lead-in study. All other subjects should complete a separate screening visit within 28 days before the first dose of study medication in the LTE.
2. Agree to apply a moisturizer at least once daily throughout the study and agree to apply the authorized topical therapy, as determined appropriate by the investigator;
3. Women of childbearing potential must agree either to be strictly abstinent throughout the study and for 12 weeks after the last study drug injection or to use an effective 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.
Effective and approved methods of contraception applicable for the subject and/or her partner are defined below:
• Progestogen-only oral hormonal contraception;
• Male or female condom;
• Cap, diaphragm, or sponge with spermicide;
• Combination of male or female condom with cap, diaphragm, or sponge with spermicide;
• Combined (estrogen- and progestogen-containing) oral, intravaginal, or transdermal hormonal contraception;
• Injectable or implanted hormonal contraception;
• Intrauterine devices;
• Bilateral tubal ligation or tube insert (such as the Essure system) at least 3 months before the study;
• Vasectomy of partner at least 3 months before the study.
4. 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;
• Documented hysterectomy or bilateral oophorectomy at least 3 months before screening.
5. Subject (and guardian, when applicable) willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol;
6. Understand and sign an informed consent form (and assent form, when applicable), before any investigational procedure(s) being performed.
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E.4 | Principal exclusion criteria |
1. Subjects who, during their participation in a prior nemolizumab study, experienced an AE which in the opinion of the investigator could indicate that continued treatment with nemolizumab may present an unreasonable risk for the subject;
2. Having received any of the treatments listed in Table 6 of the protocol within the specified timeframe before the baseline visit;
3. Pregnant women (positive pregnancy test result at screening or baseline visit), breastfeeding women, or women planning a pregnancy during the clinical study;
4. Any medical or psychological condition at the screening visit 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);
5. Planning or expected to have a major surgical procedure during the clinical study;
6. Subjects unwilling to refrain from using prohibited medications during the clinical study;
Additional Exclusion Criteria: For subjects who do not rollover from a prior nemolizumab study within 28 days of completing final study assessments or who discontinued study drug before completing the treatment period during the lead-in study:
7. Body weight < 30 kg;
8. Subjects with a history of asthma meeting 1 or more of the following criteria:
8a. Had an asthma exacerbation requiring hospitalization in the preceding 12 months;
8b. Reporting asthma that has been not well controlled (ie, symptoms > 2 days per week, nighttime awakenings > 1-3 times per week, or some interference with normal activities) during the preceding 3 months;
8c. Asthma Control Test (ACT) ≤ 19;
8d. Peak expiratory flow < 80% of the predicted value.
9. Subjects with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis.;
10. Cutaneous infection within 1 week before the screening visit or any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 1 week before the screening visit. Subjects may be rescreened once the infection has resolved;
11. Positive serology results (hepatitis B surface antigen or hepatitis B core antibody, hepatitis C antibody, or human immunodeficiency virus antibody) at the screening visit;
12. Subjects who failed to respond clinically to previous treatment with a biologic (eg, dupilumab) or a Janus kinase inhibitor;
13. History of lymphoproliferative disease or history of malignancy of any organ system within the last 5 years, except for basal cell carcinoma, squamous cell carcinoma in situ (Bowen’s disease), actinic keratoses, or carcinoma in situ of the cervix that have been treated and have no evidence of recurrence in the last 12 weeks before the screening visit;
14. History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody) or to any of the study drug excipients;
15. History of intolerance to TCS or for whom TCS is not advisable (eg, hypersensitivity to TCS, significant skin atrophy, etc), unless TCS was not used as background therapy in the lead-in study;
16. Known active or latent tuberculosis infection;
17. Known or suspected immunosuppression or unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment;
18. History of or current confounding skin condition (eg, Netherton Syndrome, psoriasis, cutaneous T-cell lymphoma [Mycosis Fungoides or Sezary Syndrome], contact dermatitis, chronic actinic dermatitis, dermatitis herpetiformis);
19. Any clinically relevant laboratory abnormalities, such as but not limited to elevated ALT or AST (> 3 × upper limit of normal) in combination with elevated bilirubin (> 2 × upper limit of normal), at the screening visit that may put the subject at significant risk according to the investigator’s judgment, if he/she participates in the clinical study;
20. Currently participating or participated in any other study of a drug or device within the past 2 months before the screening visit, or is in an exclusion period (if verifiable) from a previous study, other than the nemolizumab for AD studies (SPR.114322, SPR.116912, SPR.118380, SPR.118169, and SPR.118161);
21. History of alcohol or substance abuse within 2 years of the screening visit.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Endpoints:
- Incidence and severity of treatment-emergent AEs throughout the study
- Incidence of serious treatment-emergent AEs throughout the study
- Incidence and severity of AEs of special interest (AESIs)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety Endpoints: throughout the study
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E.5.2 | Secondary end point(s) |
Efficacy Endpoints:
- Proportion of subjects with IGA score = 0-1 at each visit through Week 112
- Proportion of subjects with EASI-75 response at each visit through Week 112
- Change and percent change from baseline in EASI at each visit through Week 112
- Proportion of subjects with low disease activity state (ie, IGA ≤ 2) at each visit through Week 112
- Change and percent change from baseline in SCORing Atopic Dermatitis (SCORAD) score at each visit through Week 112
- Change and percent change from baseline in subject-reported pruritus using 10-cm visual analogue scale (SCORAD sub-component)
- Change and percent change from baseline in subject-reported sleep loss using 10-cm visual analogue scale (SCORAD sub-component)
- Proportion of subjects reporting low disease activity state (clear, almost clear, or mild) based on Patient Global Assessment of Disease 5-point scale at each visit up to Week 112
- Proportion of subjects satisfied with study treatment (good, very good, or excellent) based on Patient Global Assessment of Treatment 5-point Likert scale at each visit up to Week 112
- Proportion of subjects receiving any concomitant AD treatment by treatment type (eg, topical, phototherapy, systemic) throughout the treatment period
- Proportion of subjects receiving any rescue therapy by rescue treatment type at any visit during the treatment period |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Subjects from blinded studies will receive blinded treatment on Day 1 to maintain the blind |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 162 |
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 |
Austria |
Belgium |
Bulgaria |
Canada |
Czech Republic |
Estonia |
France |
Germany |
Hungary |
Italy |
Korea, Republic of |
Latvia |
Lithuania |
Netherlands |
New Zealand |
Poland |
Romania |
Singapore |
Spain |
United Kingdom |
United States |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 | 23 |