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Intraamniotic Administrations of ER004 to Male Subjects With X-linked Hypohidrotic Ectodermal Dysplasia (EDELIFE)

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ClinicalTrials.gov Identifier: NCT04980638
Recruitment Status : Recruiting
First Posted : July 28, 2021
Last Update Posted : May 2, 2022
Sponsor:
Collaborators:
Pierre Fabre Medicament (co-sponsor)
IQVIA (clinical CRO)
Information provided by (Responsible Party):
EspeRare Foundation

Tracking Information
First Submitted Date  ICMJE July 20, 2021
First Posted Date  ICMJE July 28, 2021
Last Update Posted Date May 2, 2022
Estimated Study Start Date  ICMJE April 26, 2022
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2021)
Mean sweat volume [ Time Frame: at 6 months of age (corrected age for subjects born at < 37 weeks) ]
For treated subject, mean sweat volume is collected on both forearms after local stimulation with pilocarpine (pilocarpine-induced sweating)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2021)
  • Mean sweat pore density (number/cm2) [ Time Frame: at 6 months of age (key secondary) and other timepoints : 3, 12, 18, 24, 36, 48 and 60 months(secondary) ]
    Mean sweat pore density (number/cm2) determined by direct visualization with a VivaScope® at 2 different sites on the soles of the feet (up to 12 months) or at 2 different sites on the soles of the feet and/or palms (>12 months)
  • Dental development [ Time Frame: at 6 months of age (key secondary) and other timepoints : 12, 18, 24, 36, 48 and 60 months (secondary) ]
    Dental development evaluated by the number of erupted teeth and tooth germs (palpable alveolar structures in the alveolar ridge) as determined by dental examination
  • Mean sweat volume [ Time Frame: At 3, 12, 18, 24, 36, 48, 60 months ]
    For treated subject, mean sweat volume is collected on both forearms after local stimulation with pilocarpine (pilocarpine-induced sweating)
  • Dry eye issues [ Time Frame: At different timepoints from 6 to 60 months ]
    Number of Meibomian glands, Ocular surface assessment, Tear film break-up time
  • Salivation [ Time Frame: At 60 months ]
    Saliva assessed with Quantisal oral fluid collection device
  • XLHED-related hospitalizations [ Time Frame: Up to 60 months ]
    XLHED-related hospitalisation because of hyperthermia or because of unexplained fever, respiratory, skin, eye or ear infections
  • Assessment of eczema [ Time Frame: At different timepoints from 6 to 60 months ]
    Eczema will be assessed using the EASI score
  • Incidence of TEAEs (treatment-emergent adverse events) [ Time Frame: Up to 60 months ]
  • Incidence of TESAEs (treatment-emergent serious adverse events) [ Time Frame: Up to 60 months ]
  • Incidence of TEAEs (treatment-emergent adverse events) leading to treatment discontinuation. [ Time Frame: Up to 60 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intraamniotic Administrations of ER004 to Male Subjects With X-linked Hypohidrotic Ectodermal Dysplasia
Official Title  ICMJE A Prospective, Open-label, Genotype-match Controlled, Multicenter Clinical Trial to Investigate the Efficacy and Safety of Intra-amniotic ER004 as a Prenatal Treatment for Male Subjects With XLHED
Brief Summary This is an open-label, prospective, genotype-match controlled for primary estimand, non randomized, multicenter, international Phase 2 clinical trial designed to investigate the efficacy and safety of ER004 administered intraamniotically as a treatment for unborn XLHED male subjects.
Detailed Description X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare developmental disease affecting body parts derived from the embryonal ectoderm. It is caused by a broad spectrum of mutations in the ectodysplasin A gene (EDA). The main symptoms of XLHED are hypo- or anhidrosis, oligo- or anodontia, and hypotrichosis. Current treatment options are limited to the management of disease symptoms and prevention of complications. Effective corrective treatment for XLHED remains a high unmet medical need. ER004 represents a first-in-class signaling protein replacement molecule designed for specific, high affinity binding to the endogenous EDA1 receptor (EDAR). The proposed mechanism of action of ER004 is the replacement of the missing EDA1 protein in patients with XLHED. The aim of this prospective, open-label, genotype-match controlled, multicenter Phase 2 trial is to confirm the efficacy and safety results for ER004 administered intra-amniotically in a larger cohort of subjects. The target population will consist of male XLHED fetuses/subjects with EDA mutation confirmed by genetic diagnosis of a mutation in one of the maternal EDA alleles and ultrasonographic diagnosis of a significantly reduced number of fetal tooth germs, or by documented direct genetic diagnosis of a hemizygous EDA mutation. In the main study phase, efficacy and safety of the treated subjects will be assessed up to 6 months of age and safety of the mothers will be assessed up to 1 month after delivery of the child. In long-term follow-up phase, efficacy and safety of the treated subjects will be assessed up to 5 years of age. Treated subjects sweating ability will be compared to an untreated relative from his family, when available, or from a matched controlled subject from a previous natural history.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
This is an open-label, single-arm, genotype-match controlled for primary estimand, non randomized study. The primary efficacy outcome will be compared to genotype matched untreated male relatives with XLHED or to genotype-matched controls from an external XLHED database (clinical and natural history studies from which untreated genotype-matched controls will be identified).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)
Intervention  ICMJE Biological: ER004
Intra-amniotic route 100 mg/kg of estimated fetal weight per injection. 3 injections, approximately 3 weeks apart starting from gestational week 26
Study Arms  ICMJE Experimental: ER004
Human immunoglobulin G1 constant region - human ectodysplasin-A1 receptor binding domain fusion protein.
Intervention: Biological: ER004
Publications * Schneider H, Faschingbauer F, Schuepbach-Mallepell S, Körber I, Wohlfart S, Dick A, Wahlbuhl M, Kowalczyk-Quintas C, Vigolo M, Kirby N, Tannert C, Rompel O, Rascher W, Beckmann MW, Schneider P. Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia. N Engl J Med. 2018 Apr 26;378(17):1604-1610. doi: 10.1056/NEJMoa1714322.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 22, 2021)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2029
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

For mother: Adult mother with confirmed pregnancy no later than week 23+6 and genetically confirmed as carrier of an EDA mutation

  • For fetal Subject : Male Fetal subject with confirmed diagnosis of XLHED
  • For untreated relative: Untreated male relative subject ages between 6 months and 60 years with the same EDA mutation as the treated subject

Exclusion Criteria:

  • For mother: Any evidence of active maternal infection associated with a risk of preterm birth and/or congenital anomalies of prenatal and postnatal risk to the child. Documented maternal HIV infection. Any pre-existing maternal medical condition that increases the risk of preterm birth or increases the risk of a serious untoward event occurring to the mother during pregnancy. Any pregnancy disorder associated with an increased risk of preterm birth, and/or maternal, fetal or neonatal morbidity/mortality.
  • For fetal Subject : Second major anatomic anomaly (not related to the underlying XLHED) that contributes to a significant morbidity or mortality risk, or echocardiogram or ultrasonography or other findings that indicate a high risk of fetal demise or risk of preterm birth. Any condition other than XLHED that is likely to have an impact on the number of tooth germs. Any other medical condition which in the opinion of the investigator would not allow for safe conduct of the study for the subject, or that would interfere with efficacy assessments.
  • For untreated relative: Carrier of an hypomorphic EDA mutation. Known hypersensitivity to pilocarpine or pilocarpine-like muscarinic agonists. Presence of an implanted device (e.g., defibrillator, neurostimulator, pacemaker). Previous treatment with the study intervention by any route of administration prior to study start.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Pregnant female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Florence Porte-Thormé, PharmD +41 22 794 4004 Info.er004@esperare.org
Contact: Athmane Bouroubi, MD +33 5 34 50 60 00 contact.edelife@pierre-fabre.com
Listed Location Countries  ICMJE France,   Germany,   Italy,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04980638
Other Study ID Numbers  ICMJE ER004-CLIN01/F60082AI201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party EspeRare Foundation
Study Sponsor  ICMJE EspeRare Foundation
Collaborators  ICMJE
  • Pierre Fabre Medicament (co-sponsor)
  • IQVIA (clinical CRO)
Investigators  ICMJE
Principal Investigator: Holm Schneider, MD University Erlangen-Nürnberg Erlangen, Germany
PRS Account EspeRare Foundation
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP