Long-term study to assess the safety and efficacy of Nemolizumab in subjects with Atopic Dermatitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Galderma S.A.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

1 Oct 2020 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514404-13-00

EudraCT number

2019-001889-15

ClinicalTrials.gov

NCT03989206

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Others, Efficacy

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).

Secondary objectives 1

1. The secondary objective is to assess the long-term efficacy of Nemolizumab (CD14152) in adult and adolescent subjects with moderate-to-severe AD

Conditions and MedDRA coding

Atopic Dermatitis

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001624-PIP01-14

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Adolescent subjects (aged 12-17) who have not participated in a previous nemolizumab study (selected countries/selected sites – See Appendix 3) 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 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], 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). *In Germany only, subjects who may benefit from study participation are those who experienced at least 10% reduction in EASI or at least 1-point reduction in IGA score from baseline at the last visit in the prior nemolizumab study. 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. Enrollment of subjects aged 12 to 17 years has been open after the IDMC has assessed interim safety data from the phase 2 study (SPR.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 study sites confirming that the study is open for enrollment of adolescents. Adolescents could not be enrolled in the study until such communication was received.
2. 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. 3. Women of childbearing potential (ie, fertile, following menarche and until becoming post-menopausal 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)* Note: “Double barrier methods” refers to simultaneous use of a physical barrier by each partner. Use of a single barrier method (e.g., condom) together with a spermicide is not acceptable. *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. 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 NOTE: bilateral tubal ligation is not accepted as a reason for non-childbearing potential.
5. 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. 6. Understand and sign an informed consent form (and assent form, when applicable), before any investigational procedure(s) being performed. Additional Inclusion Criteria: For adolescent subjects (age 12-17) who have not participated in a previous clinical study with nemolizumab only (selected countries/selected sites).
7. 7. 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.
8. 8. EASI score ≥ 16 at both the screening and baseline visits.
9. 9. 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.
10. 10. AD involvement ≥ 10% of body surface area (BSA) at both the screening and baseline visits. Note: BSA to be derived from the SCORAD
11. 11. SCORAD pruritus VAS score of at least 4.0 at the screening and baseline visit. SCORAD pruritus VAS is completed by the subject as a single assessment of their average pruritus symptoms over the past 3 days or nights on a scale from 0 to 10.
12. 12. Documented recent history (within 6 months before the screening visit) of inadequate response to topical medications (TCS with or without TCI).

Exclusion criteria 21

1. 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. In Czech Republic only, 1 is revised: 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. 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. 2. Having received any of the treatments in Table 10 within the specified timeframe before the baseline visit.
3. 3. Pregnant women (positive pregnancy test result at screening or baseline visit), breastfeeding women, or women planning a pregnancy during the clinical study.
4. 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. 5. Planning or expected to have a major surgical procedure during the clinical study.
6. 6. Subjects unwilling to refrain from using prohibited medications during the clinical study.
7. Additional Exclusion Criteria: For new adolescent subjects or for subjects who do not rollover from a prior nemolizumab study within 28 days of completing final study assessments during the lead-in study: 7. Body weight < 30 kg. In Czech Republic only, 7 applies to all subjects.
8. 8. Subjects meeting 1 or more of the following criteria at screening 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 per 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. Peak expiratory flow < 80% of the predicted value. Note: In the event that PEF is  80% of the predicted value at the screening visit, PEF testing can be repeated once within 48 hours: • For subjects without a history of asthma • For subjects with a history of asthma but if the ACT score is >19 at screening.
9. 9. Subjects with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis.
10. 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 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 8.3.5.2. Note: Subjects with chronic, stable use of prophylactic treatment for recurrent herpes viral infection can be included in this study.
11. 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. 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. 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. 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. 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, if applicable.
16. 16. Known active or untreated latent tuberculosis infection.
17. 17. Known or suspected immunosuppression or unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment.
18. 18. 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).
19. 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), 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. 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, SPR.118161, SPR.201591, and SPR.201593).
21. 21. History of alcohol or substance abuse within 6 months of the screening visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Incidence and severity of treatment-emergent Aes throughout the study
2. Incidence of serious treatment-emergent Aes throughout the study
3. Incidence and severity of Aes of special interest (AESIs) throughout the study

Secondary endpoints 18

1. Proportion of subjects with IGA score = 0-1 at each visit through Week 200
2. • Proportion of subjects with EASI-75 response at each visit through Week 200
3. Change and percent change from baseline in EASI at each visit through Week 200
4. Proportion of subjects with low disease activity state (ie, IGA ≤ 2) at each visit through Week 200
5. Change and percent change from baseline in SCORing Atopic Dermatitis (SCORAD) score at each visit through Week 200
6. Change and percent change from baseline in subject-reported pruritus using 10-cm visual analogue scale (SCORAD sub-component) to Week 200
7. Change and percent change from baseline in subject-reported sleep loss using 10-cm visual analogue scale (SCORAD sub-component) to Week 200
8. 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
9. 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
10. Change from baseline in Dermatology Life Quality Index (DLQI) or Children’s DLQI (cDLQI) total score at each visit through Week 200
11. Change from baseline in Patient-Oriented Eczema Measure (POEM) total score at each visit through Week 200
12. Change from baseline in Hospital Anxiety and Depression Scale (HADS) for each subscale (i.e., depression and anxiety) at each visit through Week 200
13. 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
14. Change from baseline in EuroQoL 5-Dimension (EQ-5D) at each visit through Week 200
15. Proportion of subjects receiving any rescue therapy by rescue treatment type (e.g., topical, phototherapy, systemic) at any visit during the treatment period
16. 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])
17. Duration of remission (time to first relapse in subjects with IGA=0 or 1 at baseline in the LTE)
18. Time to permanent study drug discontinuation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Galderma S.A.

Sponsor organisation

Galderma S.A.

Address

Zahlerweg 10

City

Zug

Postcode

6300

Country

Switzerland

Scientific contact point

Organisation

Galderma S.A.

Contact name

Senior Medical Expert

Public contact point

Organisation

Galderma S.A.

Contact name

Senior Medical Expert

Third parties 9

Locations

14 EU/EEA countries · 113 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 207 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

23 submissions — initial application plus substantial / non-substantial modifications