Clinical trial NCT01947907: Safety, PK/PD (Pharmacokinetics/Pharmacodynamics) and Efficacy of ACP-001 Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)
Official title: A Multicenter, Phase 2, Randomized, Open Label, Active-controlled, Parallel-group Study Investigating the Safety, Tolerability, and Efficacy of Different Dose Levels of ACP-001 Administered Once Weekly Versus Standard Daily rhGH Replacement Therapy in Pre-pubertal Children With Growth Hormone Deficiency (GHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Growth Hormone Deficiency (GHD)
Keywords: Human Growth Hormone
rhGH
hGH
GHD
Lead sponsor: Ascendis Pharma A/S
Sponsor class: INDUSTRY
First posted: 2013-09-23
Enrollment: 53
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A six month study of ACP-001, a long-acting growth hormone product, versus standard human growth hormone therapy. ACP-001 will be given once-a-week, standard human growth hormone (hGH) will be given on a daily basis. The primary aim is to demonstrate safety, pharmacokinetics and pharmacodynamics over a period of six months. A secondary objective is the comparison of height velocity (HV) of the ACP-001 treated groups to the daily hGH treatment group.


Eligibility criteria: Inclusion Criteria:

* Prepubertal children, Tanner stage 1
* Diagnosis of GHD, confirmed by two stimulation tests
* Bone age not greater than chronological age
* Impaired height and height velocity
* BMI within +/- 2 SD (standard deviations)
* Baseline IGF-1 (insulin-like growth factor)
* Normal fundoscopy
* Stable hormonal replacement therapy (other than hGH)
* Written Informed Consent

Exclusion Criteria:

* Prior exposure to rhGH or IGF-I
* Past or present intracranial tumor; history or presence of malignant disease
* Small for gestational age (SGA)
* Malnutrition
* Psychosocial dwarfism
* Coeliac disease
* Anti-hGH antibodies
* Diabetes mellitus
* Chromosomal abnormalities (e.g. Turner syndrome, SHOX)
* Closed epiphyses
* Known or suspected HIV infection

Primary outcomes:
measure: Incidence of Anti-hGH Binding Antibody Formation
timeFrame: Visit 2 - Visit 5
measure: Incidence of Anti-hGH Neutralizing Antibody Formation
timeFrame: Visit 2 - Visit 5
measure: Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)
timeFrame: Start of study treatment through Visit 5 (Week 27)
measure: Cmax of hGH
timeFrame: 0 hours to 168 hours at Visit 3 (Week 13)
measure: AUC0-168h of hGH
timeFrame: 0 hours to 168 hours at Visit 3 (Week 13)
measure: E-Trough of IGF-1
timeFrame: 0 hours to 168 hours at Visit 3 (Week 13)
measure: Emax of IGF-1
timeFrame: 0 hours to 168 hours at Visit 3 (Week 13)
measure: AUEC0-168h of IGF-1
timeFrame: 0 hours to 168 hours at Visit 3 (Week 13)
Secondary outcomes:
measure: Annualized Height Velocity
timeFrame: Baseline to 6 months (Visit 5)
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: 2nd Children City Clinic
city: Varna
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Marina"
city: Ústí nad Labem
country: Czech Republic
facility: Masaryk´s Hospital
city: Alexandria
country: Egypt
facility: El Shatby University Hospital
city: Cairo
country: Egypt
facility: Ain Shams University Hospital
city: Cairo
country: Egypt
facility: Cairo University Hospital
city: El Mansoura
country: Egypt
facility: El Mansoura University Hospital
city: Bordeaux
country: France
facility: Hôpital des enfants Pellegrin
city: Lille
country: France
facility: Hôpital Jeanne de Flandre
city: Lyon
country: France
facility: Hôpital Femme-Mère-Enfant
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Magdeburg
country: Germany
facility: University Children's Hospital Magdeburg
city: Athens
country: Greece
facility: Children's Hospital of Athens "P. A. Kyriakou"
city: Budapest
country: Hungary
facility: Buda Children's Hospital
city: Budapest
country: Hungary
facility: Heim Pal Children's Hospital
city: Pecs
country: Hungary
facility: University of Pecs
city: Szeged
country: Hungary
facility: University of Szeged
city: Katowice
country: Poland
facility: University Medical Hospital
city: Lublin
country: Poland
facility: Medical University of Lublin
city: Rzeszów
country: Poland
facility: Regional Hospital N°2 Rzeszow
city: Warsaw
country: Poland
facility: Children's Memorial Health Institute Warsaw
city: Cluj- Napoca
country: Romania
facility: Emergency Clinical Hospital Cluj-Napoca
city: Iasi
country: Romania
facility: St. Spiridon County Clinic Emergency Hospital
city: Timisoara
country: Romania
facility: Louis Turcanu Emergency Hospital for Children Timisoara
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution
city: Samara
country: Russian Federation
facility: Samara State Medical University
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Pediatric Medical Academy
city: Ufa
country: Russian Federation
facility: Bashkir State Medical University
city: Ljubljana
country: Slovenia
facility: Children's University Hospital
city: Ankara
country: Turkey
facility: Ankara University School of Medicine
city: Izmir
country: Turkey
facility: Ege Üniversity
city: Donetsk
country: Ukraine
facility: Donetsk Regional Children Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Kharkiv National Medical University
city: Kiev
country: Ukraine
facility: Institute of Endocrinology and Metabolism
city: Kiev
country: Ukraine
facility: Ukrainian Children Specialized Clinical Hospital
city: Odessa
country: Ukraine
facility: Odessa National Medical University
Study officials:
affiliation: University of Lyon
name: Pierre Chatelain, Prof, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ascendis Pharma A/S
name: Michael Beckert, MD
role: STUDY_DIRECTOR
References:
citation: Chatelain P, Malievskiy O, Radziuk K, Senatorova G, Abdou MO, Vlachopapadopoulou E, Skorodok Y, Peterkova V, Leff JA, Beckert M; TransCon GH Working Group. A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency. J Clin Endocrinol Metab. 2017 May 1;102(5):1673-1682. doi: 10.1210/jc.2016-3776.