Back to resultsSafety, PK/PD (Pharmacokinetics/Pharmacodynamics) and Efficacy of ACP-001 Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)
Primary Purpose
Growth Hormone Deficiency (GHD)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ACP-001
Human Growth Hormone
Sponsored by
About this trial
This is an interventional treatment trial for Growth Hormone Deficiency (GHD) focused on measuring Human Growth Hormone, rhGH, hGH, GHD
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
Sites / Locations
- 2nd Children City Clinic
- University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Marina"
- Masaryk´s Hospital
- El Shatby University Hospital
- Ain Shams University Hospital
- Cairo University Hospital
- El Mansoura University Hospital
- Hôpital des enfants Pellegrin
- Hôpital Jeanne de Flandre
- Hôpital Femme-Mère-Enfant
- University Hospital Leipzig
- University Children's Hospital Magdeburg
- Children's Hospital of Athens "P. A. Kyriakou"
- Buda Children's Hospital
- Heim Pal Children's Hospital
- University of Pecs
- University of Szeged
- University Medical Hospital
- Medical University of Lublin
- Regional Hospital N°2 Rzeszow
- Children's Memorial Health Institute Warsaw
- Emergency Clinical Hospital Cluj-Napoca
- St. Spiridon County Clinic Emergency Hospital
- Louis Turcanu Emergency Hospital for Children Timisoara
- Federal State Budgetary Institution
- Samara State Medical University
- St. Petersburg State Pediatric Medical Academy
- Bashkir State Medical University
- Children's University Hospital
- Ankara University School of Medicine
- Ege Üniversity
- Donetsk Regional Children Clinical Hospital
- Kharkiv National Medical University
- Institute of Endocrinology and Metabolism
- Ukrainian Children Specialized Clinical Hospital
- Odessa National Medical University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
ACP-001, dose-level 1
ACP-001, dose-level 2
ACP-001, dose-level 3
Human Growth Hormone
Arm Description
Once weekly subcutaneous injection of ACP-001
Once weekly subcutaneous injection of ACP-001
Once weekly subcutaneous injection of ACP-001
Once daily subcutaneous injection of human Growth Hormone (rhGH)
Outcomes
Primary Outcome Measures
Incidence of Anti-hGH Binding Antibody Formation
Number of subjects with positive results for anti-hGH binding antibodies at two consecutive post-dose visits
Incidence of Anti-hGH Neutralizing Antibody Formation
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)
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.
Cmax of hGH
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)
AUC0-168h of hGH
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)
E-Trough of IGF-1
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 13
Emax of IGF-1
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
AUEC0-168h of IGF-1
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 13
Secondary Outcome Measures
Annualized Height Velocity
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01947907
Brief Title
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
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascendis Pharma A/S
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Growth Hormone Deficiency (GHD)
Keywords
Human Growth Hormone, rhGH, hGH, GHD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ACP-001, dose-level 1
Arm Type
Experimental
Arm Description
Once weekly subcutaneous injection of ACP-001
Arm Title
ACP-001, dose-level 2
Arm Type
Experimental
Arm Description
Once weekly subcutaneous injection of ACP-001
Arm Title
ACP-001, dose-level 3
Arm Type
Experimental
Arm Description
Once weekly subcutaneous injection of ACP-001
Arm Title
Human Growth Hormone
Arm Type
Active Comparator
Arm Description
Once daily subcutaneous injection of human Growth Hormone (rhGH)
Intervention Type
Drug
Intervention Name(s)
ACP-001
Intervention Description
Once weekly subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Human Growth Hormone
Other Intervention Name(s)
Somatropin
Intervention Description
Once daily subcutaneous injection of human Growth Hormone
Primary Outcome Measure Information:
Title
Incidence of Anti-hGH Binding Antibody Formation
Description
Number of subjects with positive results for anti-hGH binding antibodies at two consecutive post-dose visits
Time Frame
Visit 2 - Visit 5
Title
Incidence of Anti-hGH Neutralizing Antibody Formation
Description
Number of subjects with positive results for anti-hGH neutralizing antibodies at two consecutive post-dose visits
Time Frame
Visit 2 - Visit 5
Title
Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)
Description
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.
Time Frame
Start of study treatment through Visit 5 (Week 27)
Title
Cmax of hGH
Description
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)
Time Frame
0 hours to 168 hours at Visit 3 (Week 13)
Title
AUC0-168h of hGH
Description
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)
Time Frame
0 hours to 168 hours at Visit 3 (Week 13)
Title
E-Trough of IGF-1
Description
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 13
Time Frame
0 hours to 168 hours at Visit 3 (Week 13)
Title
Emax of IGF-1
Description
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
Time Frame
0 hours to 168 hours at Visit 3 (Week 13)
Title
AUEC0-168h of IGF-1
Description
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 13
Time Frame
0 hours to 168 hours at Visit 3 (Week 13)
Secondary Outcome Measure Information:
Title
Annualized Height Velocity
Description
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
Time Frame
Baseline to 6 months (Visit 5)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre Chatelain, Prof, MD
Organizational Affiliation
University of Lyon
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Beckert, MD
Organizational Affiliation
Ascendis Pharma A/S
Official's Role
Study Director
Facility Information:
Facility Name
2nd Children City Clinic
City
Minsk
Country
Belarus
Facility Name
University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Marina"
City
Varna
Country
Bulgaria
Facility Name
Masaryk´s Hospital
City
Ústí nad Labem
Country
Czech Republic
Facility Name
El Shatby University Hospital
City
Alexandria
Country
Egypt
Facility Name
Ain Shams University Hospital
City
Cairo
Country
Egypt
Facility Name
Cairo University Hospital
City
Cairo
Country
Egypt
Facility Name
El Mansoura University Hospital
City
El Mansoura
Country
Egypt
Facility Name
Hôpital des enfants Pellegrin
City
Bordeaux
Country
France
Facility Name
Hôpital Jeanne de Flandre
City
Lille
Country
France
Facility Name
Hôpital Femme-Mère-Enfant
City
Lyon
Country
France
Facility Name
University Hospital Leipzig
City
Leipzig
Country
Germany
Facility Name
University Children's Hospital Magdeburg
City
Magdeburg
Country
Germany
Facility Name
Children's Hospital of Athens "P. A. Kyriakou"
City
Athens
Country
Greece
Facility Name
Buda Children's Hospital
City
Budapest
Country
Hungary
Facility Name
Heim Pal Children's Hospital
City
Budapest
Country
Hungary
Facility Name
University of Pecs
City
Pecs
Country
Hungary
Facility Name
University of Szeged
City
Szeged
Country
Hungary
Facility Name
University Medical Hospital
City
Katowice
Country
Poland
Facility Name
Medical University of Lublin
City
Lublin
Country
Poland
Facility Name
Regional Hospital N°2 Rzeszow
City
Rzeszów
Country
Poland
Facility Name
Children's Memorial Health Institute Warsaw
City
Warsaw
Country
Poland
Facility Name
Emergency Clinical Hospital Cluj-Napoca
City
Cluj- Napoca
Country
Romania
Facility Name
St. Spiridon County Clinic Emergency Hospital
City
Iasi
Country
Romania
Facility Name
Louis Turcanu Emergency Hospital for Children Timisoara
City
Timisoara
Country
Romania
Facility Name
Federal State Budgetary Institution
City
Moscow
Country
Russian Federation
Facility Name
Samara State Medical University
City
Samara
Country
Russian Federation
Facility Name
St. Petersburg State Pediatric Medical Academy
City
St. Petersburg
Country
Russian Federation
Facility Name
Bashkir State Medical University
City
Ufa
Country
Russian Federation
Facility Name
Children's University Hospital
City
Ljubljana
Country
Slovenia
Facility Name
Ankara University School of Medicine
City
Ankara
Country
Turkey
Facility Name
Ege Üniversity
City
Izmir
Country
Turkey
Facility Name
Donetsk Regional Children Clinical Hospital
City
Donetsk
Country
Ukraine
Facility Name
Kharkiv National Medical University
City
Kharkiv
Country
Ukraine
Facility Name
Institute of Endocrinology and Metabolism
City
Kiev
Country
Ukraine
Facility Name
Ukrainian Children Specialized Clinical Hospital
City
Kiev
Country
Ukraine
Facility Name
Odessa National Medical University
City
Odessa
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
28201598
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.
Results Reference
derived
Learn more about this trial
Safety, PK/PD (Pharmacokinetics/Pharmacodynamics) and Efficacy of ACP-001 Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)
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