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

NCT ID: NCT04980638

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-26
• Study Completion Date: 2032-12-31

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.

Conditions

X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ER004

Human immunoglobulin G1 constant region - human ectodysplasin-A1 receptor binding domain fusion protein.

Group Type: EXPERIMENTAL

ER004

Intervention Type: BIOLOGICAL

Intra-amniotic route 100 mg/kg of estimated fetal weight per injection. 3 injections, approximately 3 weeks apart starting from gestational week 26

Interventions

ER004

Intra-amniotic route 100 mg/kg of estimated fetal weight per injection. 3 injections, approximately 3 weeks apart starting from gestational week 26

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pierre Fabre Medicament

INDUSTRY

Sponsor Role: collaborator

Iqvia Pty Ltd

INDUSTRY

Sponsor Role: collaborator

EspeRare Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Holm Schneider, MD

Role: PRINCIPAL_INVESTIGATOR

University Erlangen-Nürnberg Erlangen, Germany

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status: RECRUITING

Washington University

St Louis, Missouri, United States

Site Status: RECRUITING

Hôpital Necker - Enfants Malades

Paris, Paris, France

Site Status: RECRUITING

Universitaetsklinikum Erlangen

Erlangen, Bavaria, Germany

Site Status: RECRUITING

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony, Germany

Site Status: RECRUITING

IRCCS Ca' Granda Ospedale Policlinico

Milan, , Italy

Site Status: RECRUITING

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Site Status: RECRUITING

University Hospital of Wales Cardiff and Vale University Local Health

Cardiff, , United Kingdom

Site Status: RECRUITING

Countries

United States; France; Germany; Italy; Spain; United Kingdom

Central Contacts

Agnes Jaulent

Role: CONTACT

Info.er004@esperare.org

+41 22 794 4004

Marlène Guiraud

Role: CONTACT

contact.edelife@pierre-fabre.com

+33 5 34 50 60 00

Facility Contacts

Role: primary

ClinicalTrials@cshs.org

(310)-423-8965

Dorothy Grange

Role: primary

grangedk@wustl.edu

Christine Bodemer

Role: primary

christine.bodemer@aphp.fr

Holm Schneider

Role: primary

holm.schneider@uk-erlangen.de

Holger Stepan

Role: primary

holger.stepan@uniklinik-leipzig.de

Riccardo Cavalli

Role: primary

riccardo.cavalli@policlinico.mi.it

Encarnacion Guillen Navarro

Role: primary

guillen.encarna@gmail.com

Angus Clarke

Role: primary

ClarkeAJ@cardiff.ac.uk

References

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.

Reference Type: BACKGROUND

PMID: 29694819 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36672894 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37108325 (View on PubMed)

Related Links

http://www.EDELIFEklinischestudie.com/

EDELIFE Study website (Germany)

http://www.essaicliniqueEDELIFE.com/

EDELIFE Study website (France)

http://www.ensayoclinicoEDELIFE.com/

EDELIFE Study website (Spain)

http://www.EDELIFEclinicaltrial.com/

EDELIFE Study website (UK)

http://www.studioclinicoEDELIFE.com

EDELIFE Study website (Italy)

http://www.EDELIFEclinicaltrial.com/

EDELIFE Study website (USA)

Other Identifiers

ER004-CLIN01/F60082AI201

Identifier Type: -

Identifier Source: org_study_id