NEMOLIZUMAB for Atopic dermatitis

Inclusion criteria

• {"criterion_text":"- 1.\tAdolescent 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.\tSubjects 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.\tSubjects who completed the maintenance period (Week 48 visit) in a Phase 3 pivotal study (SPR.118161 or SPR.118169); OR c.\tSubjects who completed the treatment period (Week 16 visit) in the Phase 2 vaccination safety study (SPR.118380); OR d.\tSubjects who completed the treatment period (Week 16 visit) in the Phase 2 adolescent PK/safety study (SPR.116912); OR e.\tSubjects 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.\tSubjects 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.\tSubjects who completed the treatment period (Week 16) in the Phase 3b study (SPR.201591); OR h.\tSubjects 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."}
• {"criterion_text":"- 10.\tAD involvement ≥ 10% of body surface area (BSA) at both the screening and baseline visits. Note: BSA to be derived from the SCORAD"}
• {"criterion_text":"- 11.\tSCORAD 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."}
• {"criterion_text":"- 12.\tDocumented recent history (within 6 months before the screening visit) of inadequate response to topical medications (TCS with or without TCI)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 3.\tWomen 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: •\tProgestogen-only oral hormonal contraception •\tCombination 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. •\tCombined (estrogen- and progestogen-containing) oral, intravaginal, or transdermal hormonal contraception •\tInjectable or implanted hormonal contraception •\tIntrauterine devices or intrauterine hormone-releasing system •\tBilateral tubal ligation or tube insert (such as the Essure system) at least 3 months before the study •\tBilateral vasectomy of partner at least 3 months before the study"}
• {"criterion_text":"- 4.\tFemale subjects of non-childbearing potential must meet one of the following criteria: •\tAbsence 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 •\tDocumented 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."}
• {"criterion_text":"- 5.\tSubject (and guardian, when applicable) willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol."}
• {"criterion_text":"- 6.\tUnderstand 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)."}
• {"criterion_text":"- 7.\tChronic 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."}
• {"criterion_text":"- 8.\tEASI score ≥ 16 at both the screening and baseline visits."}
• {"criterion_text":"- 9.\tIGA 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."}

Exclusion criteria

• {"criterion_text":"- 1.\tSubjects 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 •\tworsening or recurrence of asthma •\trecurrent or severe infections during the lead-in study where continued exposure to study drug would pose unacceptable risk to the subject."}
• {"criterion_text":"- 10.\tCutaneous 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."}
• {"criterion_text":"- 11.\tPositive 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."}
• {"criterion_text":"- 12.\tSubjects 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)."}
• {"criterion_text":"- 13.\tHistory 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."}
• {"criterion_text":"- 14.\tHistory of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody) or to any of the study drug excipients."}
• {"criterion_text":"- 15.\tHistory 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."}
• {"criterion_text":"- 16.\tKnown active or untreated latent tuberculosis infection."}
• {"criterion_text":"- 17.\tKnown or suspected immunosuppression or unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment."}
• {"criterion_text":"- 18.\tPresence 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)."}
• {"criterion_text":"- 19.\tAny 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."}
• {"criterion_text":"- 2.\tHaving received any of the treatments in Table 10 within the specified timeframe before the baseline visit."}
• {"criterion_text":"- 20.\tCurrently 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)."}
• {"criterion_text":"- 21.\tHistory of alcohol or substance abuse within 6 months of the screening visit."}
• {"criterion_text":"- 3.\tPregnant women (positive pregnancy test result at screening or baseline visit), breastfeeding women, or women planning a pregnancy during the clinical study."}
• {"criterion_text":"- 4.\tAny 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)."}
• {"criterion_text":"- 5.\tPlanning or expected to have a major surgical procedure during the clinical study."}
• {"criterion_text":"- 6.\tSubjects unwilling to refrain from using prohibited medications during the clinical study."}
• {"criterion_text":"- 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.\tBody weight < 30 kg. In Czech Republic only, 7 applies to all subjects."}
• {"criterion_text":"- 8.\tSubjects 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: •\tFor subjects without a history of asthma •\tFor subjects with a history of asthma but if the ACT score is >19 at screening."}
• {"criterion_text":"- 9.\tSubjects with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis."}

Primary endpoints

• {"endpoint_text":"- Incidence and severity of treatment-emergent Aes throughout the study","definition_or_measurement_approach":"Incidence and severity captured by reporting treatment-emergent adverse events (AEs) throughout the study period (safety monitoring)."}
• {"endpoint_text":"- Incidence of serious treatment-emergent Aes throughout the study","definition_or_measurement_approach":"Serious treatment-emergent AEs recorded and assessed throughout the study period (seriousness criteria per ICH/GCP)."}
• {"endpoint_text":"- Incidence and severity of Aes of special interest (AESIs) throughout the study","definition_or_measurement_approach":"AESIs identified and their incidence and severity recorded throughout the study (events of special interest predefined in protocol)."}

Secondary endpoints

• {"endpoint_text":"- Proportion of subjects with IGA score = 0-1 at each visit through Week 200","definition_or_measurement_approach":"Clinical assessment of Investigator's Global Assessment (IGA) at each visit; proportion achieving score 0–1 evaluated at each visit through Week 200."}
• {"endpoint_text":"- •\tProportion of subjects with EASI-75 response at each visit through Week 200","definition_or_measurement_approach":"EASI scores assessed at visits; proportion achieving ≥75% improvement from baseline (EASI-75) at each visit through Week 200."}
• {"endpoint_text":"- Change and percent change from baseline in EASI at each visit through Week 200","definition_or_measurement_approach":"Absolute and percent change in Eczema Area and Severity Index (EASI) from baseline measured at each visit through Week 200."}
• {"endpoint_text":"- Proportion of subjects with low disease activity state (ie, IGA ≤ 2) at each visit through Week 200","definition_or_measurement_approach":"IGA assessment at visits; proportion with IGA ≤2 reported at each visit through Week 200."}
• {"endpoint_text":"- Change and percent change from baseline in SCORing Atopic Dermatitis (SCORAD) score at each visit through Week 200","definition_or_measurement_approach":"SCORAD total score measured at each visit; absolute and percent change from baseline through Week 200."}
• {"endpoint_text":"- Change and percent change from baseline in subject-reported pruritus using 10-cm visual analogue scale (SCORAD sub-component) to Week 200","definition_or_measurement_approach":"Subject-reported pruritus (10-cm VAS, SCORAD sub-component) recorded at visits; change and percent change from baseline to Week 200."}
• {"endpoint_text":"- Change and percent change from baseline in subject-reported sleep loss using 10-cm visual analogue scale (SCORAD sub-component) to Week 200","definition_or_measurement_approach":"Subject-reported sleep loss (10-cm VAS, SCORAD sub-component) recorded at visits; change and percent change from baseline to Week 200."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Patient Global Assessment of Disease (5-point scale) completed at visits; proportion reporting low disease activity (clear/almost clear/mild) at each visit through Week 200."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Patient Global Assessment of Treatment (5-point Likert) at visits; proportion reporting good/very good/excellent at each visit through Week 200."}
• {"endpoint_text":"- Change from baseline in Dermatology Life Quality Index (DLQI) or Children’s DLQI (cDLQI) total score at each visit through Week 200","definition_or_measurement_approach":"DLQI or cDLQI administered at visits; change from baseline in total score assessed through Week 200."}
• {"endpoint_text":"- Change from baseline in Patient-Oriented Eczema Measure (POEM) total score at each visit through Week 200","definition_or_measurement_approach":"POEM questionnaire completed by subjects at visits; change from baseline in total score evaluated through Week 200."}
• {"endpoint_text":"- Change from baseline in Hospital Anxiety and Depression Scale (HADS) for each subscale (i.e., depression and anxiety) at each visit through Week 200","definition_or_measurement_approach":"HADS completed at visits; change from baseline reported for anxiety and depression subscales through Week 200."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"WPAI:AD instrument administered at visits; change from baseline for work productivity and activity impairment subscales through Week 200."}
• {"endpoint_text":"- Change from baseline in EuroQoL 5-Dimension (EQ-5D) at each visit through Week 200","definition_or_measurement_approach":"EQ-5D completed at visits; change from baseline assessed at each visit through Week 200."}
• {"endpoint_text":"- Proportion of subjects receiving any rescue therapy by rescue treatment type (e.g., topical, phototherapy, systemic) at any visit during the treatment period","definition_or_measurement_approach":"Recording of rescue therapy use by type at visits; proportion of subjects receiving rescue therapy by type during treatment period."}
• {"endpoint_text":"- 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])","definition_or_measurement_approach":"Time-to-event analysis from baseline to first relapse as defined; relapse triggering rescue therapy per investigator judgment."}
• {"endpoint_text":"- Duration of remission (time to first relapse in subjects with IGA=0 or 1 at baseline in the LTE)","definition_or_measurement_approach":"Duration measured as time from baseline to first relapse in the subgroup with IGA=0 or 1 at LTE baseline."}
• {"endpoint_text":"- Time to permanent study drug discontinuation","definition_or_measurement_approach":"Time-to-event from first dose to permanent discontinuation of study drug recorded."}

Methods

• Training portal and patient recruitment (Neonstone Limited listed as third party with duty: Training Portal and Patient recruitment).
• Country-specific recruitment arrangements submitted as K1 recruitment documents (K1_Recruitment arrangements files present for multiple countries).
• SMS-based consent and withdrawal materials and SMS text messaging for participant communications (L1/L2 SMS Consent and SMS Withdrawal documents present in multiple countries).
• Site-based recruitment via participating hospitals/clinics listed in country site lists (hospital and clinic sites in each Member State).

Austria

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

14-10-2024

Processing Time Days

61

Number Of Sites

2

Number Of Participants

29

Belgium

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

29-08-2024

Processing Time Days

15

Number Of Sites

4

Number Of Participants

16

Bulgaria

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

13-09-2024

Processing Time Days

30

Number Of Sites

8

Number Of Participants

60

Czechia

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

03-09-2024

Processing Time Days

20

Number Of Sites

6

Number Of Participants

109

Germany

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

03-09-2024

Processing Time Days

20

Number Of Sites

23

Number Of Participants

212

Estonia

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

02-09-2024

Processing Time Days

19

Number Of Sites

2

Number Of Participants

12

Spain

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

30-08-2024

Processing Time Days

16

Number Of Sites

11

Number Of Participants

52

France

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

02-09-2024

Processing Time Days

19

Number Of Sites

4

Number Of Participants

29

Hungary

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

28-08-2024

Processing Time Days

14

Number Of Sites

4

Number Of Participants

30

Italy

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

04-09-2024

Processing Time Days

21

Number Of Sites

4

Number Of Participants

11

Lithuania

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

13-09-2024

Processing Time Days

30

Number Of Sites

2

Number Of Participants

8

Latvia

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

16-09-2024

Processing Time Days

33

Number Of Sites

4

Number Of Participants

39

Netherlands

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

28-08-2024

Processing Time Days

14

Number Of Sites

1

Number Of Participants

5

Poland

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

05-10-2024

Processing Time Days

52

Number Of Sites

32

Number Of Participants

552

Primary sponsor

Full Name

Galderma S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Paragon Global CRS B.V.

Responsibilities

patients reimbursement

Name

AG Mednet Inc.

Responsibilities

Adjudication Committee (IAC)

Name

Eurofins Central Laboratory B.V.

Responsibilities

laboratory services

Name

WCG Clinical Inc.

Responsibilities

SUSAR Distribution

Name

Neonstone Limited

Responsibilities

Training Portal and Patient recruitment

Name

Intrinseque Health Pte Ltd

Responsibilities

IMP/NIMP drug collection and destruction in Italy

Name

Eresearchtechnology Inc.

Responsibilities

eCOA / ePRO and Cardiac Safety

Name

Syneos Health Inc.

Responsibilities

multiple operational CRO-like responsibilities (codes listed in sponsor duties)

Name

Medidata Solutions Inc.

Responsibilities

data platform services

Third parties

• {"country":"Netherlands","full_name":"Paragon Global CRS B.V.","duties_or_roles":"patients reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"AG Mednet Inc.","duties_or_roles":"Adjudication Committee (IAC)","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"laboratory services (code 4)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"SUSAR Distribution","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Neonstone Limited","duties_or_roles":"Training Portal and Patient recruitment","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Singapore","full_name":"Intrinseque Health Pte Ltd","duties_or_roles":"IMP/NIMP drug collection and destruction in Italy","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"electronic Clinical Outcome Analysis (eCOA) / electronic patient reported outcome (ePRO) and Cardiac Safety","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"multiple operational roles (codes 10,11,12,13,2,5,6,8) as listed in sponsor duties","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"data platform services (code 3)","organisation_type":"Non-Pharmaceutical company"}