Safety, PK/PD (Pharmacokinetics/Pharmacodynamics) and Efficacy of ACP-001 Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)
- Conditions
- Growth Hormone Deficiency (GHD)
- Interventions
- Registration Number
- NCT01947907
- Lead Sponsor
- Ascendis Pharma A/S
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ACP-001, dose-level 1 ACP-001 Once weekly subcutaneous injection of ACP-001 ACP-001, dose-level 2 ACP-001 Once weekly subcutaneous injection of ACP-001 ACP-001, dose-level 3 ACP-001 Once weekly subcutaneous injection of ACP-001 Human Growth Hormone Human Growth Hormone Once daily subcutaneous injection of human Growth Hormone (rhGH)
- Primary Outcome Measures
Name Time Method Cmax of hGH 0 hours to 168 hours at Visit 3 (Week 13) As part of the following endpoint:
PK profile of serum hGH from ACP-001 treated patients compared between ACP-001 dose groups and to the pharmacokinetic (PK) profile of hGH from the daily rhGH groups during visit 1 and 3.
Uncorrected Cmax (maximum value of concentration) values at Visit 3 (Week 13)Incidence of Anti-hGH Binding Antibody Formation Visit 2 - Visit 5 Number of subjects with positive results for anti-hGH binding antibodies at two consecutive post-dose visits
Incidence of Anti-hGH Neutralizing Antibody Formation Visit 2 - Visit 5 Number of subjects with positive results for anti-hGH neutralizing antibodies at two consecutive post-dose visits
Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator) Start of study treatment through Visit 5 (Week 27) Assessment of local tolerability was performed by examining injection sites (by the investigator during study visits) and on the basis of anamnestic data and records in the Patient Diary. Assessments included pain, redness, bruising, swelling, and itching. Every subject was counted only once within each symptom category.
AUC0-168h of hGH 0 hours to 168 hours at Visit 3 (Week 13) As part of the following endpoint:
PK profile of serum hGH from ACP-001 treated patients compared between ACP-001 dose groups and to the PK profile of hGH from the daily rhGH group during Visit 1 and Visit 3
Uncorrected AUC0-168h (area under the curve from 0h to 168h) values at Visit 3 (Week 13)AUEC0-168h of IGF-1 0 hours to 168 hours at Visit 3 (Week 13) As part of the following endpoint:
PD profile of serum IGF-1 during V1 and V3 compared between the ACP-001 dose groups and to the rhGH group.
Uncorrected AUEC0-168 (area under the efficacy curve from 0h-168h) values at Week 13E-Trough of IGF-1 0 hours to 168 hours at Visit 3 (Week 13) As part of the following endpoint:
PD profile of serum IGF-1 during Visit 1 and Visit 3 compared between the ACP-001 dose groups and to the daily rhGH group
Uncorrected E-Trough (the pre-dose efficacy response) values at Week 13Emax of IGF-1 0 hours to 168 hours at Visit 3 (Week 13) As part of the following endpoint:
PD profile of serum IGF-1 during V1 and V3 compared between the ACP-001 dose groups and to the daily rhGH group
- Secondary Outcome Measures
Name Time Method Annualized Height Velocity Baseline to 6 months (Visit 5) Annualized HV during treatment with ACP-001 or daily rhGH at the end of 6 months, for each ACP-001 dose group and for the daily rhGH dose group
Trial Locations
- Locations (36)
Kharkiv National Medical University
🇺🇦Kharkiv, Ukraine
Institute of Endocrinology and Metabolism
🇺🇦Kiev, Ukraine
Donetsk Regional Children Clinical Hospital
🇺🇦Donetsk, Ukraine
Odessa National Medical University
🇺🇦Odessa, Ukraine
St. Spiridon County Clinic Emergency Hospital
🇷🇴Iasi, Romania
Masaryk´s Hospital
🇨🇿Ústà nad Labem, Czech Republic
Children's University Hospital
🇸🇮Ljubljana, Slovenia
Louis Turcanu Emergency Hospital for Children Timisoara
🇷🇴Timisoara, Romania
Emergency Clinical Hospital Cluj-Napoca
🇷🇴Cluj- Napoca, Romania
Children's Hospital of Athens "P. A. Kyriakou"
🇬🇷Athens, Greece
Ain Shams University Hospital
🇪🇬Cairo, Egypt
Cairo University Hospital
🇪🇬Cairo, Egypt
2nd Children City Clinic
🇧🇾Minsk, Belarus
University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Marina"
🇧🇬Varna, Bulgaria
El Mansoura University Hospital
🇪🇬El Mansoura, Egypt
University Hospital Leipzig
🇩🇪Leipzig, Germany
Hôpital des enfants Pellegrin
🇫🇷Bordeaux, France
Heim Pal Children's Hospital
ðŸ‡ðŸ‡ºBudapest, Hungary
Hôpital Jeanne de Flandre
🇫🇷Lille, France
Medical University of Lublin
🇵🇱Lublin, Poland
St. Petersburg State Pediatric Medical Academy
🇷🇺St. Petersburg, Russian Federation
Ankara University School of Medicine
🇹🇷Ankara, Turkey
Ukrainian Children Specialized Clinical Hospital
🇺🇦Kiev, Ukraine
Hôpital Femme-Mère-Enfant
🇫🇷Lyon, France
El Shatby University Hospital
🇪🇬Alexandria, Egypt
University of Szeged
ðŸ‡ðŸ‡ºSzeged, Hungary
University of Pecs
ðŸ‡ðŸ‡ºPecs, Hungary
Regional Hospital N°2 Rzeszow
🇵🇱Rzeszów, Poland
Children's Memorial Health Institute Warsaw
🇵🇱Warsaw, Poland
Ege Ãœniversity
🇹🇷Izmir, Turkey
Federal State Budgetary Institution
🇷🇺Moscow, Russian Federation
Samara State Medical University
🇷🇺Samara, Russian Federation
Bashkir State Medical University
🇷🇺Ufa, Russian Federation
Buda Children's Hospital
ðŸ‡ðŸ‡ºBudapest, Hungary
University Children's Hospital Magdeburg
🇩🇪Magdeburg, Germany
University Medical Hospital
🇵🇱Katowice, Poland