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
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.
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.
21 studies on the registry are indexed under Ectodermal Dysplasia 1, Anhidrotic; 1 is open to participants now.
Browse Ectodermal Dysplasia 1, Anhidrotic studies →EspeRare Foundation is the lead sponsor of 2 studies on the registry; 1 is open to participants now.
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For mother: adult mother with confirmed pregnancy no later than week 23+6 and genetically confirmed as carrier of an EDA mutation
Exclusion Criteria:
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.
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.
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.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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)
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)
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)
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
Number of Meibomian glands
Number of Meibomian glands in the lower eyelids determined by Meibography
Time frame: At 6 and 60 months of age
Ocular surface assessment
Ocular surface assessment (normal, keratitis superficialis punctate) by eye using fluorescein
Time frame: At 24, 48 and 60 months of age
Tear film break-up time
Tear film break-up time (seconds) determined using fluorescein
Time frame: 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
Time frame: At 60 months of age
Salivation
Saliva (volume and flow rate) assessed with Quantisal oral fluid collection device
Time frame: 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
Time frame: Up to 60 months of age
Assessment of eczema
Eczema will be assessed using the EASI score
Time frame: At different timepoints from 6 to 60 months of age
Incidence of TEAEs (treatment-emergent adverse events)
Number of subjets with TEAEs
Time frame: Up to 60 months of age
Incidence of TESAEs (treatment-emergent serious adverse events)
Number of subjects with TESAEs
Time frame: 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
Time frame: Up to 60 months of age
Plan to share: No
Started Apr 2022 (actual). Primary completion is estimated for Feb 2027, 58 months after the start.
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Studies of the drug tested here: Fc-EDA
Ectodermal Dysplasia 1, Anhidrotic →
EspeRare Foundation