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

NCT04980638 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ER004-CLIN01/F60082AI201
• Study Type: interventional
• Target: 20
• Locations: 6 countries
• Sites: 8

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.

Conditions

X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Mean sweat pore density (number/cm2)

  at 6 months of age (key secondary) and other timepoints : 3, 12, 18, 24, 36, 48 and 60 months of age (secondary)

• Dental development

  at 6 months of age (key secondary) and other timepoints : 12, 18, 24, 36, 48 and 60 months of age (secondary)

• Mean sweat volume

  At 3, 12, 18, 24, 36, 48, 60 months of age

• Number of Meibomian glands

  At 6 and 60 months of age

• Ocular surface assessment

  At 24, 48 and 60 months of age

Study Arms (1)

ER004

EXPERIMENTAL

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

Biological: ER004

Interventions

ER004 BIOLOGICAL

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

ER004

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pregnant female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• EspeRare Foundation: lead
• Pierre Fabre Medicament: collaborator
• Iqvia Pty Ltd: collaborator

Study Sites (8)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Hôpital Necker - Enfants Malades

Paris, Paris, 75743, France

RECRUITING

Universitaetsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

RECRUITING

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony, 04103, Germany

RECRUITING

IRCCS Ca' Granda Ospedale Policlinico

Milan, 20122, Italy

RECRUITING

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

University Hospital of Wales Cardiff and Vale University Local Health

Cardiff, CF14 4XW, United Kingdom

RECRUITING

Related Publications (3)

• 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.

  PMID: 29694819 BACKGROUND

• 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.

  PMID: 36672894 BACKGROUND

• 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.

  PMID: 37108325 BACKGROUND

Related 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)

MeSH Terms

Conditions

Ectodermal Dysplasia 1, Anhidrotic

Condition Hierarchy (Ancestors)

Ectodermal Dysplasia; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Abnormalities; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Holm Schneider, MD

  University Erlangen-Nürnberg Erlangen, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Agnes Jaulent

CONTACT

+41 22 794 4004; Info.er004@esperare.org

Marlène Guiraud

CONTACT

+33 5 34 50 60 00; contact.edelife@pierre-fabre.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: July 28, 2021
• Study Start: April 26, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): December 1, 2032
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); DE (2); ES (1); FR (1); GB (1); US (2)