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

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Brief Title

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

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

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Mean sweat volume

Secondary Outcome

 Mean sweat pore density (number/cm2)

Condition

X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)

Intervention

ER004

Study Arms / Comparison Groups

 ER004
Description:  Human immunoglobulin G1 constant region - human ectodysplasin-A1 receptor binding domain fusion protein.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

20

Start Date

October 1, 2021

Completion Date

April 2029

Primary Completion Date

June 2023

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 ages between 6 months and 60
             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.
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Holm Schneider, MD, +41 22 794 4004, [email protected]



Administrative Informations


NCT ID

NCT04980638

Organization ID

ER004-CLIN01/F60082AI201


Responsible Party

Sponsor

Study Sponsor

EspeRare Foundation

Collaborators

 Pierre Fabre Medicament (co-developer)

Study Sponsor

Holm Schneider, MD, Principal Investigator, University Erlangen-Nürnberg Erlangen, Germany


Verification Date

July 2021