Clinical trial NCT01992289: Extension Study of XLHED-Affected Male Subjects Treated With EDI200 in Protocol ECP-002
Official title: Extension Study of XLHED-Affected Male Subjects Treated With EDI200 in Protocol ECP-002
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: X-linked Hypohidrotic Ectodermal Dysplasia
Keywords: XLHED
HED
Hypohidrotic ectodermal dysplasia
Christ-Siemens-Touraine Syndrome
Lead sponsor: Edimer Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-11-25
Enrollment: 10
Sex: MALE
Minimum age (years): 6
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is an open-label extension study without additional study drug administration on as many as 10 XLHED-affected males previously having received EDI200 in the ECP-002 trial. XLHED-affected male infants who completed the ECP-002 trial will be followed with yearly visits starting at age 1 year.

Brief summary: The goal of the ECP-002e extension study is to continue the evaluation of all EDI200-treated ECP-002 subjects up to age 10 yrs. No additional study drug administration is planned. The efficacy evaluations will incorporate growth and development parameters, frequency of infections and hospitalizations, and age-appropriate assessments of ectoderm-derived organ function. The safety evaluations will include physical examinations, adverse events and concomitant medication documentation, and laboratory testing. Funding Source - FDA OOPD

Detailed description: X-linked hypohidrotic ectodermal dysplasia (XLHED) is a disorder of ectoderm development in which sweat and other secretory gland hypoplasias predispose affected infants to serious and potentially life-threatening hyperthermia and pneumonia. Those XLHED patients who survive infancy face a host of ectoderm-related clinical conditions including failure to thrive, oligodontia and misshapen teeth, mid-face hypoplasia, eczema, chronic dry eyes, asthma, respiratory infections, sinusitis and chronic nosebleeds. XLHED is caused by inherited defects in the ectodysplasin gene (EDA, www.ncbi.nlm.nih.gov/omim) resulting in a deficiency of the ectoderm signaling protein EDA-A1. As is the general case with X-linked disorders, hemizygous XLHED males are more consistently and severely affected, while heterozygous XLHED females have a more variable phenotype.

In normal development, EDA-A1 acts as an ectoderm signaling molecule that binds specifically to the EDA-A1 receptor (EDAR) triggering initiation and maturation of ectodermal appendages into sweat and other secretory glands, tooth buds and hair follicles. In the case of XLHED, EDA-A1 deficiency results in the absence or functional hypoplasia of the ectoderm appendages. There are no therapies currently available for XLHED that prevent or correct the underlying ectodermal abnormalities.

EDI200 is a fully humanized EDA-A1 replacement molecule under development as a novel therapeutic for XLHED. EDI200 comprises the human IgG1 Fc domain linked to the human EDA-A1 receptor-binding domain. On-target EDI200 activation of the EDA-A1/EDAR signaling pathway in vivo is evidenced by the remarkable phenotypic response in preclinical models. In XLHED-affected animals, EDA-A1 deficiency is corrected by a single course of EDI200 therapy, administered either prenatally (mice) or postnatally (newborn mice and dogs), resulting in a significant and sustained improvement in the health of the treated animals. Postnatal studies in both mice and dogs demonstrated a consistent and restricted window of efficacy. These results support the clinical development of EDI200 as a therapeutic to be administered to XLHED-affected patients in the neonatal period or earlier.

ECP-002, a Phase 2, international, first-in-neonate EDI200 study is enrolling treatment-naïve, XLHED-affected male newborns in the first two weeks of life. All subjects will meet entry criteria including documentation of an EDA mutation associated with XLHED. Following Baseline evaluations, EDI200 dosing is initiated between day-of-life 2 and 14, with each study subject receiving a single course of study drug administered at 2 doses/week for a total of 5 doses. The treatment study protocol incorporates comprehensive safety, pharmacokinetic (PK), immunogenetic, and pharmacodynamic (PD)/efficacy evaluations continuing through age 6 months.

The goal of the ECP-002e extension study is to continue the evaluation of all EDI200-treated ECP-002 subjects up to age 10 yrs. No additional study drug administration is planned. The efficacy evaluations will incorporate growth and development parameters, frequency of infections and hospitalizations, and age-appropriate assessments of ectoderm-derived organ function. The safety evaluations will include physical examinations, adverse events and concomitant medication documentation, and laboratory testing.

Eligibility criteria: Inclusion Criteria:

Subjects must meet all of the following criteria to be enrolled:

1. Subject received at least one dose of EDI200 in the neonate study ECP-002
2. Written informed consent of parent(s)

Exclusion Criteria:

Subjects who meet any of the following criteria may not be enrolled in this study:

1. Medically-significant postnatal complications or congenital anomalies outside of those considered to be associated with the diagnosis of XLHED
2. Major protocol violations during enrollment in study ECP-002 as determined by the Sponsor

Primary outcomes:
measure: Growth and development
timeFrame: Annually up to age 10 years
measure: Dentition
timeFrame: Change from baseline dentition at 2, 5 and 10 years
Secondary outcomes:
measure: Mortality
timeFrame: Annually up to age 10 years
measure: Hospitalizations
timeFrame: Annually up to age 10 years
measure: Infections
timeFrame: Annually up to age 10 years
measure: Unexplained fevers
timeFrame: Annually up to age 10 years
measure: Heat intolerance
timeFrame: Annually up to age 10 years
measure: Sweat gland density
timeFrame: Annually up to age 10 years
measure: Sweat function
timeFrame: Annually up to age 10 years
measure: Skin health
timeFrame: Annually up to age 10 years
measure: Hair growth
timeFrame: Change from baseline hair growth at 5 and 10 years
measure: Respiratory health
timeFrame: Annually up to age 10 years
measure: Ocular health
timeFrame: Annually up to age 10 years
measure: Number of participants with adverse events
timeFrame: Annually up to age 10 years
Other outcomes:
measure: Craniofacial development
timeFrame: Annually up to age 10 years
measure: Exercise thermoregulation
timeFrame: Change from baseline exercise thermoregulation at 7, 8, 9 or 10 years (done once)
measure: Immunogenicity
timeFrame: Change from baseline immunogenicity at 2 years
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Washington, D.C.
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bavaria
city: Milan
country: Italy
facility: Azienda Ospedaliera-Polo Universitario "Luigi Sacco"
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
Study officials:
affiliation: Edimer Pharmaceuticals
name: Kenneth Huttner, MD, PhD
role: STUDY_DIRECTOR
References: