E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 10040785 - Skin and subcutaneous tissue disorders |
|
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). |
|
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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adolescent subjects (aged 12-17) who have not participated in a
previous nemolizumab study (selected countries/selected sites) or
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 the phase 3 pivotal study (Protocol 118169 or 118161) and do not qualify for the maintenance period; OR
b. Subjects who completed the maintenance period (Week 48 visit) in the phase 3 pivotal protocol;OR
c. Subjects who required rescue medication, as determined by the investigator, in either the phase 3 initial treatment or maintenance periods.Subjects receiving rescue med. must complete a required wait period prior to LTE participation (Week 16 visit, for subjects receiving rescue in the initial treatment period; Week 32 visit, for subjects receiving rescue in the maintenance period). No wait is required for rescue received after Week 32, provided the subject meets all eligibility criteria.To maintain the blind of ongoing phase 3 studies, the IRT will not restrict enrollment into the LTE study based on prior treatment assigned (in the phase 3 study). Subjects with prior rescue treatment who rollover should be closely monitored by the investigator to assess the benefit of continued participation compared to observed or potential risks (as there is a chance that these subjects were previously assigned to receive active drug in the lead-in study and therefore may not receive add. therapeutic benefit in the LTE study);OR
d. Subjects who completed the treatment period (Week 16 visit) in the phase 2 PK/safety study (Protocol 116912);OR
e. Subjects who participated in the Nemolizumab phase 2b AD study (Protocol 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], SPR.114322 [Week 24], SPR.201591 [Week 16], and SPR.201593 [Week 13] unless the subject experienced an AE that may present an unreasonable risk if study medication is continued;OR
g. Subjects who completed the treatment period (Week 16) in the Phase 3b study (SPR.201591);OR
h. Subjects who completed the treatment period (Week 13) in the Phase 2 DDI study (SPR.201593)
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 (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 child bearing 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 an adequate and approved 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
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; confirmed with follicle stimulating hormone (FSH) level in the postmenopausal range;
- Documented hysterectomy, bilateral salpingectomy, 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.
Additional Inclusion Criteria: see protocol
|
|
E.4 | Principal exclusion criteria |
1. Subjects who, during 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.
In Czech Rep. only, 1 is revised:
1. Subjects who, during 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.
Subjects who experienced
• worsening or recurrence of asthma
• recurrent or severe infections
during the lead-in study where continued exposure to study drug would pose unacceptable risk to the subject.
2. Having received any of the treatments listed in Table 10 within the specified timeframe before the baseline visit;
3. Pregnant women, 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 assess. (eg, poor venous access or needle-phobia);
5. Planning or expected to have a major surgical procedure during the study;
6. Subjects unwilling to refrain from using prohibited medications during the study;
Add. Exclusion Criteria: For new adolescents or for subjects who do not rollover from a prior nemolizumab study within 28 days of completing final study assessments in the lead-in study:
7. Body weight < 30 kg;
In Czech Rep. only, 7 applies to all subjects.
8. Subjects meeting 1 or more of the following criteria at screen. or
baseline: 8a. Had an asthma exacerbation requiring hospitalization in the preceding 12 months;8b. Reporting asthma that has been not well controlled (ie, symptoms occurring on > 2 days per week, nighttime awakenings 2 or more times a week, or some interference with normal activities) during the preceding 3 months;
8c. Asthma Control Test (ACT) ≤ 19; (only for subjects with a history of asthma);
8d. PEF < 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 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 COVID-19 within 2 weeks before the screening or baseline visit. Subjects may be rescreened once the infection has resolved. Resolution of COVID-19 can be confirmed by recovery assessment methods, as described in Section 8.3.5.2.;
11. Positive serology results (hepatitis B surface antigen [HBsAg] or
hepatitis B core antibody [HBcAb], hepatitis C [HCV] antibody with
positive HCV RNA, or human immunodeficiency virus [HIV] antibody) at the screening visit;
12. 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);
13. 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 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, or 2) actinic keratoses that have been treated;
14. History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody);
15. History of intolerance to TCS or for whom TCS is not advisable,
unless TCS was not used as background therapy in the lead-in study, if applicable;
16. Known active or untreated latent tuberculosis infection;
17. Known or suspected immunosuppression or unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment;
18. Presence of confounding skin condition that may interfere with study assessments;
19. Any clinically relevant lab. 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), 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;
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, other than the nemolizumab for AD studies (SPR.114322, SPR.116912, SPR.118380, SPR.118169, and SPR.118161,SPR.201591, and SPR.201593).
21. History of alcohol or substance abuse within 6 months of the screening visit.
|
|
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) throughout
the study
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety Endpoints: throughout the study
|
|
E.5.2 | Secondary end point(s) |
Efficacy Endpoints:
- Proportion of subjects with IGA score = 0-1 at each visit through Week 200
- Proportion of subjects with EASI-75 response at each visit through Week 200
- Change and percent change from baseline in EASI at each visit through Week 200
- Change and percent change from baseline in IGA score at each visit through Week 200
- Proportion of subjects with low disease activity state (ie, IGA ≤ 2) at each visit through Week 200
- Change and percent change from baseline in SCORing Atopic Dermatitis (SCORAD) score at each visit through Week 200
- 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 200
- 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 200
-Change from baseline in Dermatology Life Quality Index (DLQI) or
Children's DLQI (cDLQI) total score at each visit through Week 200
- Change from baseline in Patient-Oriented Eczema Measure (POEM)
total score at each visit through Week 200
- Change from baseline in Hospital Anxiety and Depression Scale (HADS) for each subscale (i.e., depression and anxiety) at each visit through Week 200
- Change from baseline in Work Productivity and Activity Impairment:
Atopic Dermatitis (WPAI:AD) for each subscale (i.e., work productivity
and activity impairment) at each visit through Week 200
- Change from baseline in EuroQoL 5-Dimension (EQ-5D) at each visit
through Week 200
- Proportion of subjects receiving any rescue therapy by rescue
treatment type (e.g., topical, phototherapy, systemic) at any visit during the treatment period;
- Time to first relapse (relapse is defined as: worsening of AD requiring rescue therapy, if judged to be medically necessary by the investigator [i.e, clinically significant worsening of signs and/or symptoms of AD])
- Duration of remission (time to first relapse in subjects with IGA=0 or 1 at baseline in the LTE)
- Time to permanent study drug discontinuation |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
As specified within the list of endpoints |
|
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 |
|
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 the Phase 3 studies will receive blinded treatment on Day 1 to maintain the blind |
|
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 215 |
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 |
New Zealand |
Singapore |
Korea, Democratic People's Republic of |
Australia |
Canada |
Georgia |
United Kingdom |
United States |
Austria |
Belgium |
Bulgaria |
Czechia |
Estonia |
France |
Germany |
Hungary |
Italy |
Latvia |
Lithuania |
Netherlands |
Poland |
Spain |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 13 |