An open-label Phase 2 trial to investigate efficacy and safety of intraamniotic administrations of ER004 to male subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pierre Fabre Medicament, Fondation EspeRare

Participant type

Pediatric, Patients

Age range

In Utero

Gender

Male

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

2 Dec 2021 → ongoing

Decision date (initial)

2024-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pierre Fabre Médicament

External identifiers

EU CT number

2024-512632-30-00

EudraCT number

2021-002532-23

ClinicalTrials.gov

NCT04980638

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To assess the efficacy of intra-amniotic administrations of ER004 on sweating ability in male XLHED subjects with a null mutation in EDA at 6 months of age, compared to untreated matched control subjects.

Secondary objectives 5

1. To assess the efficacy of intra-amniotic administrations of ER004 on sweat pore density and dentition in male subjects with XLHED at 6 months of age
2. To assess the efficacy of intra-amniotic administrations of ER004 in male subjects with XLHED up to 5 years of age
3. To assess the safety of intra-amniotic administrations of ER004 in male subjects with XLHED up to 6 months of age and in mothers up to 1 month after delivery
4. To assess the long-term safety of intra-amniotic administrations of ER004 in male subjects with XLHED up to 5 years of age
5. To assess safety parameters in untreated relatives (controls)

Conditions and MedDRA coding

X-linked hypohidrotic ectodermal dysplasia (XLHED)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. For mother : Adult mother with confirmed pregnancy no later than week 23+6 days and genetically confirmed as carrier of an EDA mutation
2. For fetus subject: Male Fetal subject with confirmed diagnosis of XLHED
3. Untreated relative : Untreated male relative subject ages between 6 months and 75 years with the same EDA mutation as the treated subject

Exclusion criteria 10

1. 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.
2. For mother: 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.
3. For mother: Any pregnancy disorder associated with an increased risk of preterm birth, and/or maternal, fetal or neonatal morbidity/mortality
4. 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
5. For fetal subject: Any condition other than XLHED (i.e., other forms of ectodermal dysplasia, large orofacial clefts) that is likely to have an impact on the number of tooth germs.
6. For fetal subject: 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 (e.g., any disorders that lead to reduced fetal swallowing).
7. For Untreated Relative: Carrier of an hypomorphic EDA mutation.
8. For Untreated Relative: Known hypersensitivity to pilocarpine or pilocarpine-like muscarinic agonists.
9. For Untreated Relative: Presence of an implanted device (e.g., defibrillator, neurostimulator, pacemaker).
10. For Untreated Relative: Previous treatment with the study intervention by any route of administration prior to study start.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean sweat volume collected on both forearms after local stimulation with pilocarpine (pilocarpine-induced sweating).

Secondary endpoints 11

1. Mean sweat pore density (number/cm2) determined by direct visualization with a VivaScope® at 6 months of age (V8) at 2 different sites on the soles of the feet
2. Dental development evaluated by the number of erupted teeth and tooth buds (palpable alveolar structures in the alveolar ridge) as determined by oral examination at 6 months of age (V8)
3. Mean sweat volume on both forearms measured from a pilocarpineinduced sweat test (at other timepoints than 6 months).
4. Sweat pore density (at other timepoints than 6 months).
5. Dentition (at other timepoints than 6 months).
6. Dry eye
7. Salivation assessment
8. Number of XLHED related hospitalizations
9. Assessment of eczema
10. Safety and tolerability assessments
11. Health-related quality of life assessments

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pierre Fabre Medicament

Sponsor organisation

Pierre Fabre Medicament

Address

Les Cauquillous

City

Lavaur

Postcode

81500

Country

France

Scientific contact point

Organisation

Pierre Fabre Medicament

Contact name

Clinical trial Information

Public contact point

Organisation

Pierre Fabre Medicament

Contact name

Clinical trial Information

Third parties 5

Fondation EspeRare

Sponsor organisation

Fondation EspeRare

Address

Avenue De Secheron 15

City

Geneva

Postcode

1202

Country

Switzerland

Third parties 6

Sponsor responsibilities

Article 77 compliance

Pierre Fabre Medicament

Contact point sponsor

Pierre Fabre Medicament

Article 77 implementation

Pierre Fabre Medicament

Locations

4 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 203 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications