A Pilot Multicentric Open Study Assessing the Efficacy and Safety of NEMOlizumab in Patients ≥ 12yo With Dystrophic Epidermolysis Bullosa (NEMODE)
Dystrophic epidermolysis bullosa (DEB) is an inherited mucocutaneous fragility disorder caused by pathogenic variants in COL7A1, leading to blistering, scarring, and significant morbidity. Pruritus is a major complication that substantially impairs patients' quality of life, yet effective treatment options remain limited. Nemolizumab, an interleukin-31 receptor alpha antagonist, inhibits IL-31 signaling, a pathway potentially involved in DEB-associated pruritus. Elevated IL-31 levels have been reported in patients with recessive DEB (RDEB) and correlated with pruritus severity, supporting its potential role as a therapeutic target. We hypothesize that nemolizumab may represent an effective and safe treatment option for pruritus in patients with DEB.
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Descrizione dettagliata
Epidermolysis bullosa (EB) is a heterogeneous group of rare inherited disorders characterized by skin and mucosal fragility leading to the formation of blisters, erosions, and scars. It is traditionally subdivided into four main subtypes: simplex, junctional, dystrophic (EBD), and Kindler. The dystrophic form (DEB) is associated with dominant or recessive pathogenic variants in the COL7A1 gene, which encodes type VII collagen, an essential component of the anchoring fibrils that ensure dermo-epidermal adhesion.
Available epidemiological data estimate the prevalence of hereditary EB at approximately 11 cases per million people in the United States, with an incidence of about 2.72 new cases per 1 million live births. DEB accounts for approximately 25% of EB cases and can present in autosomal dominant or recessive forms.
EBD is associated with significant morbidity, particularly due to chronic complications such as pruritus and fibrosis, which significantly impair patients' quality of life and independence. To date, there is no curative treatment. Management relies on a multidisciplinary approach that is primarily symptomatic. Recently, B-VEC, a topical gene therapy designed to restore COL7A1 expression in skin lesions to promote healing, has received regulatory approval. However, its accessibility is limited
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Tipo di studio
Tipo di studio
Iscrizione (Stimato)
Iscrizione
Fase
Fase
- Fase 2
- Fase 3
Contatti e Sedi
Contatto studio
Contatto studio
- Nome: Christine CHIAVERINI, Doctor
- Numero di telefono: 0492034702
- Email: chiaverini.c@chu-nice.fr
Backup dei contatti dello studio
- Nome: Thomas HUBICHE, Doctor
- Email: hubiche.t@chu-nice.fr
Luoghi di studio
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Fr
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Nice, Fr, Francia, 06000
- CHU de Nice
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Sub-investigatore:
- Thomas HUBICHE, Doctor
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Contatto:
- Christine CHIAVERINI, Doctor
- Numero di telefono: 0492034702
- Email: causeret.m@chu-nice.fr
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France
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Paris, France, Francia, 75015
- APHP Necker
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Contatto:
- Nathalia BELLON, Doctor
- Numero di telefono: 01 42 75 48 39
- Email: nathalia.bellon@aphp.fr
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Paris, France, Francia, 75018
- APHP St Louis
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Contatto:
- Pauline BATAILLE, Doctor
- Numero di telefono: 01 42 49 40 62
- Email: pauline.bataille@aphp.fr
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Toulouse, France, Francia, 31059
- Hôpital Larrey
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Contatto:
- Maella SEVERINO-FREIRE, Doctor
- Numero di telefono: 0 33 5 67 77 18 76
- Email: severino-freire.m@chu-toulouse.fr
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Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Subject male or female
- Age ≥ 12 years old
- Subject has recessive (Severe, Intermediate, Inversa or Pruriginosa) or dominant (Intermediate or Pruriginosa) dystrophic epidermolysis bullosa, confirmed by skin immunomapping and/or molecular analysis (one or 2 COL7A1 mutation(s)), according to the last EB classification 4) Subject has at least a baseline pruritus score ≥ 4/10.
5) Subject agrees not to use any topical therapies other than the investigator approved (VYJUVEK gel is accepted if ongoing at the time of the study, excepted on the left leg) 6) A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: 7) (a) Is not a Women of Childbearing Potential (WOCBP) OR 8) Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the study period until the end of her participation to the study. Effective method of birth control recommended by the Clinical Trials Facilitation and Coordination group are combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral or intravaginal or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral or injectable or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion 9) Subject is in good general health and free of any known disease state or physical condition which, in the investigator's opinion, might impair his evaluation or which exposes the subject to an unacceptable risk by study participation.
10) Subject is willing and able to follow all study instructions and to attend all study visits.
11) Subject is able to comprehend and willing to sign an Informed Consent and/or Assent Form.
12) Affiliation with a social security scheme.
Exclusion Criteria:
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Subjects who are treated with DUPILUMAB or JAK inhibitor. A wash out of 2 months is mandatory to be included.
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Subjects with uncontrolled asthma.
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Medical History and Concurrent Diseases:
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Any major surgery within 8 weeks prior to Day 1, or any planned surgery for the first 28 weeks of the study
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Has donated blood >500mLwithin 4 weeks prior to Day1, or plans to donate blood during the course of the study
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Drug or alcohol abuse, as determined by the investigator, within 6 months prior to Day 1
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Medical marijuana or prescription marijuana taken for medicinal reasons
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Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, psychiatric, neurologic, immunologic, or local active infection/infectious illness) that, in the investigator's judgment or after consultation with the Medical Monitor or designee, will substantially increase the risk to the participant if he or she participates in the study
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Unstable cardiovascular disease, defined as a recent clinical cardiovascular event (eg, unstable angina, myocardial infarction, stroke, rapid atrial fibrillation) in the last 3 months prior to screening, or a cardiac hospitalization (eg revascularization procedure, pacemaker implantation) within 3 months prior to screening, or patients at risk of major adverse cardiovascular events, deep venous thrombosis or pulmonary embolism.
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Has uncontrolled arterial hypertension characterized by a systolic blood pressure (BP) >160 mm Hg or diastolic BP >100 mm Hg.
Note: Determined by 2 consecutive elevated readings. If an initial BP reading exceeds this limit, the BP may be repeated once after the participant has rested sitting for ≥10 minutes. If the repeat value is less than the criterion limits, the second value may be accepted.
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Class III or IV congestive heart failure by New York Heart Association Criteria
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Has cancer or history of cancer (solid organ or hematologic including myelodysplastic syndrome) or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma, or carcinoma of cervix in situ that has been treated with no evidence of recurrence)
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Any significant/uncontrolled neuropsychiatric illness as clinically judged by the investigator during
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Females of child-bearing potential who meet the following criteria for pregnancy testing:
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Subjects with a positive serum pregnancy test at the Screening Visit or a positive urine pregnancy test at Baseline prior to the first dose of study treatment (local practices may require serum pregnancy testing at Baseline).
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Subjects with a borderline serum pregnancy test at Screening must have absence of clinical suspicion of pregnancy or other pathological causes of borderline results and a serum pregnancy test ≥ 3 days later to document continued lack of a positive result (unless inclusion of subjects with a borderline pregnancy test may be prohibited by local requirements).
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Subjects with a urine pregnancy test at Baseline that is borderline or ambiguous must have a serum pregnancy test performed. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
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Female subjects of childbearing potential who are not able and/or willing to practice at least 1 protocol-specified method of birth control that is highly effective from Study Day 1 through at least 30 days after the last dose of study drug (local practices may require an additional method of contraception). Female subjects of non-childbearing potential do not need to use birth control.
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Female subjects who are pregnant, breastfeeding, or considering becoming pregnant or donating eggs during the study and for 30 days after the last dose of study drug.
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Subject has another member of her/his immediate family (i.e., living in the same household) enrolled in this study.
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Subject has used any systemic product that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study assessments within 30 days prior to Visit 1.
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Vulnerable persons as mentioned in articles L1121-5, L1121-6, L1121-7, L1121-8 and L1122-1-2 of the public health code.
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Subject has a history of sensitivity to any of the ingredients of Nemolizumab.
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Withdrawal of the informed consent.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
|---|---|
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Sperimentale: Nemolizumab will be administered as a 60 mg loading dose (two 30 mg injections) at Day 0, followed b
Neolizumab |
Nemolizumab will be administered as a 60 mg loading dose (two 30 mg injections) at Day 0, followed by 30 mg subcutaneously every 4 weeks for 24 weeks, |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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To study the efficacy of Nemolizumab on pruritus in patients > 12yo with DEB after 4 weeks of treatment, in a multicentric, prospective, and open pilot study.
Lasso di tempo: 4 weeks
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The primary endpoint will be the proportion of patients achieving a clinically meaningful improvement in pruritus severity at Week 4 compared with baseline, defined as a reduction of at least 4 points on the Peak Pruritus Numerical Rating Scale (PP-NRS), which ranges from 0 (no itch) to 10 (worst itch imaginable). |
4 weeks
|
Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
To describe the evolution of the following efficacy and health outcomes measures after 24 weeks of treatment
Lasso di tempo: at 24 weeks
|
pain (scale 0-10) |
at 24 weeks
|
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To describe the evolution of the following efficacy and health outcomes measures after 24 weeks of treatment
Lasso di tempo: at baseline
|
pain (scale 0-10) |
at baseline
|
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To describe the evolution of the following efficacy and health outcomes measures after 24 weeks of treatment
Lasso di tempo: at 24 weeks
|
quality of life (scale 0-30) |
at 24 weeks
|
|
To describe the evolution of the following efficacy and health outcomes measures after 24 weeks of treatment
Lasso di tempo: at baseline
|
quality of life (scale 0-30) |
at baseline
|
Collaboratori e investigatori
Sponsor
Sponsor
Studiare le date dei record
Studia le date principali
Inizio studio (Stimato)
Inizio studio
Completamento primario (Stimato)
Completamento primario
Completamento dello studio (Stimato)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie genetiche, congenite
- Malattie del tessuto connettivo
- Manifestazioni cutanee
- Malattie della pelle
- Anomalie congenite
- Malattie della pelle, genetiche
- Anomalie della pelle
- Malattie della pelle, vescicolobollose
- Malattie del collagene
- Malattie e anomalie congenite, ereditarie e neonatali
- Condizioni patologiche, segni e sintomi
- Malattie della pelle e del tessuto connettivo
- Segni e sintomi
- Epidermolisi Bollosa
- Epidermolisi bollosa distrofica
- Prurito
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- 26-PP-01
- 2026-526417-28-00 (Ctis)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Informazioni su farmaci e dispositivi, documenti di studio
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