X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)Phase 2EDELIFENCT04980638
Intraamniotic Administrations of ER004 to Male Subjects With X-linked Hypohidrotic Ectodermal Dysplasia
A Phase 2 study testing ER004 in people with X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED), run by EspeRare Foundation at 8 sites in 6 countries.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)
- What is being tested?
- ER004
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 8 sitesin 6 countries
- Study dates
- 26 Apr 2022to Dec 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
8 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
8 sites in 6 countries
United States2 sites, 2 recruiting
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
(310)-423-8965, ClinicalTrials@cshs.org
- Recruiting
Washington University
St Louis, Missouri, 63110
Dorothy Grange, grangedk@wustl.edu
Germany2 sites, 2 recruiting
- Recruiting
Universitaetsklinikum Erlangen
Erlangen, Bavaria, 91054
Holm Schneider, holm.schneider@uk-erlangen.de
- Recruiting
Universitaetsklinikum Leipzig AoeR
Leipzig, Saxony, 04103
Holger Stepan, holger.stepan@uniklinik-leipzig.de
France1 site, 1 recruiting
- Recruiting
Hôpital Necker - Enfants Malades
Paris, Paris, 75743
Christine Bodemer, christine.bodemer@aphp.fr
Italy1 site, 1 recruiting
- Recruiting
IRCCS Ca' Granda Ospedale Policlinico
Milan, 20122
Riccardo Cavalli, riccardo.cavalli@policlinico.mi.it
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120
Encarnacion Guillen Navarro, guillen.encarna@gmail.com
United Kingdom1 site, 1 recruiting
- Recruiting
University Hospital of Wales Cardiff and Vale University Local Health
Cardiff, CF14 4XW
Angus Clarke, ClarkeAJ@cardiff.ac.uk
About this study
Official title: 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.
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.
- Being tested
- ER004
- Medical subject headings
- Ectodermal Dysplasia 1, Anhidrotic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ER004Biological
Intra-amniotic route 100 mg/kg of estimated fetal weight per injection. 3 injections, approximately 3 weeks apart starting from gestational week 26
| Study group | Role | What they receive |
|---|---|---|
| ER004 | Experimental | Human immunoglobulin G1 constant region - human ectodysplasin-A1 receptor binding domain fusion protein. Receives: Biological: ER004 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean sweat volume
For treated subject, mean sweat volume is collected on both forearms after local stimulation with pilocarpine (pilocarpine-induced sweating)
Measured: at 6 months of age (corrected age for subjects born at < 37 weeks)
Secondary outcomes (13)
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)
Measured: 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
Measured: 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)
Measured: 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
Measured: At 6 and 60 months of age
Ocular surface assessment
Ocular surface assessment (normal, keratitis superficialis punctate) by eye using fluorescein
Measured: At 24, 48 and 60 months of age
Tear film break-up time
Tear film break-up time (seconds) determined using fluorescein
Measured: 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
Measured: At 60 months of age
Salivation
Saliva (volume and flow rate) assessed with Quantisal oral fluid collection device
Measured: 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
Measured: Up to 60 months of age
Assessment of eczema
Eczema will be assessed using the EASI score
Measured: At different timepoints from 6 to 60 months of age
Incidence of TEAEs (treatment-emergent adverse events)
Number of subjets with TEAEs
Measured: Up to 60 months of age
Incidence of TESAEs (treatment-emergent serious adverse events)
Number of subjects with TESAEs
Measured: 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
Measured: Up to 60 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2021
- Study start26 Apr 2022
- Primary completionFeb 2027 (estimated)
- Study completionDec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- EspeRare Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Pierre Fabre Medicament, IQVIA Pty Ltd
- Responsible party
- Sponsor
- Investigators
- Holm Schneider, MD, Principal investigator, University Erlangen-Nürnberg Erlangen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04980638
- Sponsor's protocol ID
- ER004-CLIN01/F60082AI201
- Acronym
- EDELIFE
- Status last verified
- Apr 2025
- First submitted
- 20 Jul 2021
- Last updated
- 30 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 29694819Schneider 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 36672894Schneider 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
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04980638
- Acronym / sponsor ID
- EDELIFE / ER004-CLIN01/F60082AI201
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- EspeRare FoundationUniversity, hospital or other
- Collaborators
- Pierre Fabre Medicament, IQVIA Pty Ltd
- Study start
- 26 Apr 2022 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Dec 2032 (estimated)
- First posted
- 28 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| ER004 | Experimental | Biological: ER004Human immunoglobulin G1 constant region - human ectodysplasin-A1 receptor binding domain fusion protein. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ER004Intra-amniotic route 100 mg/kg of estimated fetal weight per injection. 3 injections, approximately 3 weeks apart starting from gestational week 26 | Biological | ER004 |
Primary outcome
Mean sweat volume
Time frame: at 6 months of age (corrected age for subjects born at < 37 weeks)
For treated subject, mean sweat volume is collected on both forearms after local stimulation with pilocarpine (pilocarpine-induced sweating)
13 secondary outcomes
Mean sweat pore density (number/cm2)
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
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
Time frame: At 3, 12, 18, 24, 36, 48, 60 months of age
Number of Meibomian glands
Time frame: At 6 and 60 months of age
Ocular surface assessment
Time frame: At 24, 48 and 60 months of age
Tear film break-up time
Time frame: At 24, 48 and 60 months of age
Ocular Surface Disease Index (OSDI) score
Time frame: At 60 months of age
Salivation
Time frame: At 60 months of age
XLHED-related hospitalizations
Time frame: Up to 60 months of age
Assessment of eczema
Time frame: At different timepoints from 6 to 60 months of age
Incidence of TEAEs (treatment-emergent adverse events)
Time frame: Up to 60 months of age
Incidence of TESAEs (treatment-emergent serious adverse events)
Time frame: Up to 60 months of age
Incidence of TEAEs (treatment-emergent adverse events) leading to treatment discontinuation
Time frame: Up to 60 months of age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2025.
- Background: PubMed 29694819Schneider 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.
- Background: PubMed 36672894Schneider 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.
- Background: PubMed 37108325Schneider 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.
- EDELIFE Study website (Germany)Link provided by the sponsor.
- EDELIFE Study website (France)Link provided by the sponsor.
- EDELIFE Study website (Spain)Link provided by the sponsor.
- EDELIFE Study website (UK)Link provided by the sponsor.
- EDELIFE Study website (Italy)Link provided by the sponsor.
- EDELIFE Study website (USA)Link provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Holm Schneider, MD principal investigator
University Erlangen-Nürnberg Erlangen, Germany
8 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ER004 in people with X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED), run by EspeRare Foundation at 8 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Germany, France, Italy, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Agnes Jaulent (+41 22 794 4004, Info.er004@esperare.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean sweat volume (time frame: at 6 months of age (corrected age for subjects born at < 37 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04980638, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2025.