ClinicalTrials.gg
RecruitingNCT04980638EDELIFEUpdated Apr 30, 2025

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

A Phase 2 interventional study of ER004 in X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED), sponsored by EspeRare Foundation. Recruiting at 8 sites in 6 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-30.

Sponsored by EspeRare Foundation · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Apr 2022; still recruiting 4 years 6 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
20
Allocation
Not applicable
Ages
18 Years and older
Sex
Female
01

Study 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.

Read the 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.

02

Conditions studied

  • X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)
03

In context

Ectodermal Dysplasia 1, Anhidrotic

21 studies on the registry are indexed under Ectodermal Dysplasia 1, Anhidrotic; 1 is open to participants now.

Browse Ectodermal Dysplasia 1, Anhidrotic studies →

Lead sponsor

EspeRare Foundation is the lead sponsor of 2 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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 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 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.
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
20 participants (estimated)

Study arms

  • Experimental
    ER004

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

    Biological: ER004

Interventions

  • BiologicalER004

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

06

What researchers measure

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)

    Time frame: at 6 months of age (corrected age for subjects born at < 37 weeks)

Secondary outcomes

  1. 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)

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

  2. 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

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

  3. Mean sweat volume

    For treated subject, mean sweat volume is collected on both forearms after local stimulation with pilocarpine (pilocarpine-induced sweating)

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

  4. Number of Meibomian glands

    Number of Meibomian glands in the lower eyelids determined by Meibography

    Time frame: At 6 and 60 months of age

  5. Ocular surface assessment

    Ocular surface assessment (normal, keratitis superficialis punctate) by eye using fluorescein

    Time frame: At 24, 48 and 60 months of age

  6. Tear film break-up time

    Tear film break-up time (seconds) determined using fluorescein

    Time frame: At 24, 48 and 60 months of age

  7. 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

    Time frame: At 60 months of age

  8. Salivation

    Saliva (volume and flow rate) assessed with Quantisal oral fluid collection device

    Time frame: At 60 months of age

  9. XLHED-related hospitalizations

    XLHED-related hospitalisation because of hyperthermia or because of unexplained fever, respiratory, skin, eye or ear infections

    Time frame: Up to 60 months of age

  10. Assessment of eczema

    Eczema will be assessed using the EASI score

    Time frame: At different timepoints from 6 to 60 months of age

  11. Incidence of TEAEs (treatment-emergent adverse events)

    Number of subjets with TEAEs

    Time frame: Up to 60 months of age

  12. Incidence of TESAEs (treatment-emergent serious adverse events)

    Number of subjects with TESAEs

    Time frame: Up to 60 months of age

  13. Incidence of TEAEs (treatment-emergent adverse events) leading to treatment discontinuation

    Number of subjects with TEAEs leading to treatment discontinuation

    Time frame: Up to 60 months of age

07

Study locations

8 of 8 sites recruiting
08

References and documents

Publications

  • 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. PubMed 29694819 ↗
  • 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. PubMed 36672894 ↗
  • 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. PubMed 37108325 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Apr 2022 (actual). Primary completion is estimated for Feb 2027, 58 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Jul 20, 2021
First posted
Jul 28, 2021
StartActual
Apr 26, 2022
Primary completionEst.
Feb 2027
CompletionEst.
Dec 2032
Last update
Apr 30, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 30, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04980638
Lead sponsor
EspeRare Foundation
Collaborators
Pierre Fabre Medicament, Iqvia Pty Ltd
Responsible party
Sponsor
First posted
Jul 28, 2021
Start date
Apr 26, 2022
Primary completion
Feb 2027 (estimated)
Completion
Dec 2032 (estimated)
Last update
Apr 30, 2025

Study contacts

Agnes Jaulent
Contact
Info.er004@esperare.org
+41 22 794 4004
Marlène Guiraud
Contact
contact.edelife@pierre-fabre.com
+33 5 34 50 60 00
Holm Schneider, MD
principal investigator · University Erlangen-Nürnberg Erlangen, Germany

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Fc-EDA

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