Long-Term Safety and Efficacy Assessment of Nemolizumab (CD14152) in Moderate-to-Severe Atopic Dermatitis Patients

Trial ID: 2024-514404-13-00
Protocol: RD.06.SPR.118163
Sponsor: Galderma S.A.

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Diseases & Conditions

Dermatitis atopic

Objectives

The primary objective of this study is to assess the long-term **safety** of Nemolizumab (CD14152) in adult and adolescent subjects with moderate-to-severe **atopic dermatitis** (AD). Evaluating the safety profile of Nemolizumab is clinically relevant as it ensures the therapeutic agent can be used over extended periods without causing adverse effects, which is crucial for chronic conditions like atopic dermatitis.

The secondary objective is to assess the long-term efficacy of Nemolizumab in the same population. Understanding the sustained efficacy of Nemolizumab is important for determining its potential as a long-term treatment option for managing symptoms and improving the quality of life in patients with moderate-to-severe atopic dermatitis.

Participants

The clinical trial involves a total of **739 participants** diagnosed with **Atopic Dermatitis**, focusing on assessing the long-term safety of Nemolizumab in individuals with moderate-to-severe conditions. The study population includes both male and female subjects, encompassing adolescents aged 12-17 and adults. Participants were selected based on specific inclusion criteria, such as a documented history of chronic atopic dermatitis for at least two years and inadequate response to topical medications. The trial includes individuals with a **SCORAD pruritus VAS score** of at least 4.0 and an EASI score of 16 or higher. Participants are required to apply a moisturizer daily and adhere to authorized topical therapy. The study population is characterized by a vulnerable group, including adolescents, who are required to comply with contraceptive measures if of childbearing potential. The selection process ensures that participants are willing and able to comply with the study's procedural requirements, including signing informed consent. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

Plans and Procedures

The clinical trial is designed to evaluate the long-term safety and efficacy of **nemolizumab** in subjects with moderate-to-severe **atopic dermatitis**. This is a prospective, multicenter study employing a randomized, double-blind, controlled trial design. The trial is expected to span from December 18, 2019, to August 31, 2026, with participant involvement lasting up to 200 weeks. The study will include several key visits: an initial screening visit, multiple follow-up visits, and a final end-of-study visit. The screening visit will determine eligibility based on criteria such as age, disease severity, and previous treatment history. Follow-up visits will occur regularly to monitor the incidence and severity of treatment-emergent adverse events (AEs), as well as to assess secondary endpoints such as changes in disease activity and quality of life measures. The end-of-study visit will conclude the participant's involvement and gather final data on the long-term effects of the treatment.

Participants will be required to attend study visits at specified intervals, where assessments will include the Investigator's Global Assessment (IGA) score, Eczema Area and Severity Index (EASI), and other relevant measures. The primary endpoints focus on the incidence and severity of treatment-emergent AEs, serious AEs, and AEs of special interest. Secondary endpoints include the proportion of subjects achieving specific IGA and EASI scores, changes in pruritus and sleep loss, and overall satisfaction with the treatment. Participants are expected to adhere to the study protocol, including the application of moisturizers and authorized topical therapies. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of adverse events that pose an unreasonable risk to the participant. The trial aims to provide comprehensive data on the long-term safety and efficacy of **nemolizumab** for the treatment of **atopic dermatitis**.

Treatment

The clinical trial involves the administration of **Nemolizumab**, a **biological** agent, as the experimental medication. Nemolizumab is provided in the form of a **solution for injection** and is intended for **subcutaneous use**. The active substance, **nemolizumab**, is a protein of other origin, specifically designed for the treatment of moderate-to-severe **atopic dermatitis**. The maximum daily dose of Nemolizumab is 60 mg, with a total maximum dose of 1530 mg over the course of the study. The treatment period extends up to 196 days. The medication is identified by the sponsor product code CD14152 / CIM331 and is manufactured by GALDERMA S.A.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on assessing the long-term safety and efficacy of Nemolizumab in the target population. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial does not include a pediatric formulation, and the medication is not classified as an orphan drug.

Efficacy

The efficacy of Nemolizumab in the treatment of moderate-to-severe **Atopic Dermatitis** will be assessed through a series of predefined secondary endpoints. These endpoints include the proportion of subjects achieving an Investigator's Global Assessment (IGA) score of 0-1 at each visit through Week 200, indicating clear or almost clear skin. Additionally, the proportion of subjects achieving an Eczema Area and Severity Index (EASI)-75 response, which represents a 75% improvement from baseline, will be evaluated at each visit through Week 200. Changes and percent changes from baseline in EASI scores will also be measured at each visit.

Further assessments will include changes and percent changes from baseline in the SCORing Atopic Dermatitis (SCORAD) score, as well as subject-reported pruritus and sleep loss using a 10-cm visual analogue scale, all evaluated up to Week 200. The proportion of subjects reporting low disease activity state, based on the Patient Global Assessment of Disease 5-point scale, and satisfaction with study treatment, based on the Patient Global Assessment of Treatment 5-point Likert scale, will be recorded at each visit up to Week 200.

Additional efficacy parameters include changes from baseline in the Dermatology Life Quality Index (DLQI) or Children's DLQI (cDLQI), Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), Work Productivity and Activity Impairment: Atopic Dermatitis (WPAI:AD), and EuroQoL 5-Dimension (EQ-5D) scores at each visit through Week 200. The proportion of subjects receiving any rescue therapy, time to first relapse, duration of remission, and time to permanent study drug discontinuation will also be evaluated.

Inclusion and Exclusion Criteria

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Inclusion Criteria

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.
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.
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
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.
Subject (and guardian, when applicable) willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol.
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).
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.
EASI score ≥ 16 at both the screening and baseline visits.
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.
AD involvement ≥ 10% of body surface area (BSA) at both the screening and baseline visits. Note: BSA to be derived from the SCORAD
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.
Documented recent history (within 6 months before the screening visit) of inadequate response to topical medications (TCS with or without TCI).

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Exclusion Criteria

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.
Having received any of the treatments in Table 10 within the specified timeframe before the baseline visit.
Pregnant women (positive pregnancy test result at screening or baseline visit), breastfeeding women, or women planning a pregnancy during the clinical study.
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).
Planning or expected to have a major surgical procedure during the clinical study.
Subjects unwilling to refrain from using prohibited medications during the clinical study.
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.
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.
Subjects with a current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis.
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.
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.
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).
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.
History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody) or to any of the study drug excipients.
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.
Known active or untreated latent tuberculosis infection.
Known or suspected immunosuppression or unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment.
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).
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.
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).
History of alcohol or substance abuse within 6 months of the screening visit.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Austria	Not Recruiting	18 Dec 2019	29
Belgium	Not Recruiting	18 Dec 2019	16
Bulgaria	Not Recruiting	18 Dec 2019	60
Czechia	Not Recruiting	18 Dec 2019	109
Estonia	Not Recruiting	18 Dec 2019	12
France	Not Recruiting	18 Dec 2019	29
Germany	Not Recruiting	18 Dec 2019	212
Hungary	Not Recruiting	18 Dec 2019	30
Italy	Not Recruiting	18 Dec 2019	11
Latvia	Not Recruiting	18 Dec 2019	39