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

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

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.

Study Overview

• Status: Recruiting
• Conditions: X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)
• Intervention / Treatment: Biological: ER004

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: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marlène Guiraud; Phone Number: +33 5 34 50 60 00; Email: contact.edelife@pierre-fabre.com
• Study Contact Backup: Name: Agnes Jaulent; Phone Number: +41 22 794 4004; Email: Info.er004@esperare.org

Study Locations

• France
  • Paris
    • Paris Cedex 15, Paris, France, 75743
      • Recruiting
      • Hopital Necker - Enfants Malades
      • Contact: Christine Bodemer; Email: christine.bodemer@aphp.fr
• Germany
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • Recruiting
      • Universitaetsklinikum Erlangen
      • Contact: Holm Schneider; Email: holm.schneider@uk-erlangen.de
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Recruiting
      • Universitaetsklinikum Leipzig AoeR
      • Contact: Holger Stepan; Email: holger.stepan@uniklinik-leipzig.de
• Italy
  • Milan, Italy, 20122
    • Recruiting
    • IRCCS Ca' Granda Ospedale Policlinico
    • Contact: Riccardo Cavalli; Email: riccardo.cavalli@policlinico.mi.it
• Spain
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Universitario Virgen de la Arrixaca
      • Contact: Encarnacion Guillen Navarro; Email: guillen.encarna@gmail.com
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Recruiting
    • University Hospital of Wales Cardiff and Vale University Local Health
    • Contact: Angus Clarke; Email: ClarkeAJ@cardiff.ac.uk
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Contact: Phone Number: (310)-423-8965; Email: ClinicalTrials@cshs.org
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Contact: Dorothy Grange; Email: grangedk@wustl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 aged between 6 months and 75 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ER004; Human immunoglobulin G1 constant region - human ectodysplasin-A1 receptor binding domain fusion protein.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean sweat volume	For treated subject, mean sweat volume is collected on both forearms after local stimulation with pilocarpine (pilocarpine-induced sweating)	at 6 months of age (corrected age for subjects born at < 37 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean sweat pore density (number/cm2)	Mean sweat pore density (number/cm2) determined by direct visualization with a VivaScope® at 2 different sites on the sole/soles of the foot/feet (up to 12 months) or at 2 different sites on the sole/soles of the foot/feet and/or palm/palms of the hand/hands (>12 months)	at 6 months of age (key secondary) and other timepoints : 3, 12, 18, 24, 36, 48 and 60 months of age (secondary)
Dental development	Dental development evaluated by the number of erupted teeth and tooth germs (palpable alveolar structures in the alveolar ridge) as determined by dental examination	at 6 months of age (key secondary) and other timepoints : 12, 18, 24, 36, 48 and 60 months of age (secondary)
Mean sweat volume	For treated subject, mean sweat volume is collected on both forearms after local stimulation with pilocarpine (pilocarpine-induced sweating)	At 3, 12, 18, 24, 36, 48, 60 months of age
Number of Meibomian glands	Number of Meibomian glands in the lower eyelids determined by Meibography	At 6 and 60 months of age
Ocular surface assessment	Ocular surface assessment (normal, keratitis superficialis punctate) by eye using fluorescein	At 24, 48 and 60 months of age
Tear film break-up time	Tear film break-up time (seconds) determined using fluorescein	At 24, 48 and 60 months of age
Ocular Surface Disease Index (OSDI) score	Score assessed on a scale of 0 to 100 through the OSDI questionnaire. Higher scores mean a worse outcome	At 60 months of age
Salivation	Saliva (volume and flow rate) assessed with Quantisal oral fluid collection device	At 60 months of age
XLHED-related hospitalizations	XLHED-related hospitalisation because of hyperthermia or because of unexplained fever, respiratory, skin, eye or ear infections	Up to 60 months of age
Assessment of eczema	Eczema will be assessed using the EASI score	At different timepoints from 6 to 60 months of age
Incidence of TEAEs (treatment-emergent adverse events)	Number of subjets with TEAEs	Up to 60 months of age
Incidence of TESAEs (treatment-emergent serious adverse events)	Number of subjects with TESAEs	Up to 60 months of age
Incidence of TEAEs (treatment-emergent adverse events) leading to treatment discontinuation	Number of subjects with TEAEs leading to treatment discontinuation	Up to 60 months of age

Collaborators and Investigators

• Sponsor: EspeRare Foundation
• Collaborators: IQVIA Pty Ltd; Pierre Fabre Medicament
• Investigators: Principal Investigator: Holm Schneider, MD, University Erlangen-Nürnberg Erlangen, Germany

Publications and helpful links

General Publications

• Schneider H, Hadj-Rabia S, Faschingbauer F, Bodemer C, Grange DK, Norton ME, Cavalli R, Tadini G, Stepan H, Clarke A, Guillen-Navarro E, Maier-Wohlfart S, Bouroubi A, Porte F. Protocol for the Phase 2 EDELIFE Trial Investigating the Efficacy and Safety of Intra-Amniotic ER004 Administration to Male Subjects with X-Linked Hypohidrotic Ectodermal Dysplasia. Genes (Basel). 2023 Jan 6;14(1):153. doi: 10.3390/genes14010153.
• Schneider H, Faschingbauer F, Schuepbach-Mallepell S, Korber 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.
• Schneider H, Schweikl C, Faschingbauer F, Hadj-Rabia S, Schneider P. A Causal Treatment for X-Linked Hypohidrotic Ectodermal Dysplasia: Long-Term Results of Short-Term Perinatal Ectodysplasin A1 Replacement. Int J Mol Sci. 2023 Apr 12;24(8):7155. doi: 10.3390/ijms24087155.

Helpful Links

• EDELIFE Study website (Germany)
• EDELIFE Study website (France)
• EDELIFE Study website (Spain)
• EDELIFE Study website (UK)
• EDELIFE Study website (Italy)
• EDELIFE Study website (USA)

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: July 22, 2021
• First Posted (Actual): July 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Skin Diseases; Congenital Abnormalities; Abnormalities, Multiple; Skin Diseases, Genetic; Genetic Diseases, X-Linked; Skin Abnormalities; Ectodermal Dysplasia; Ectodermal Dysplasia 1, Anhidrotic
• Other Study ID Numbers: ER004-CLIN01/F60082AI201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No