Safety, PK/PD (Pharmacokinetics/Pharmacodynamics) and Efficacy of ACP-001 Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Growth Hormone Deficiency (GHD)

Intervention / Treatment
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* Drug: ACP-001
* Drug: Human Growth Hormone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACP-001, dose-level 1<br>Once weekly subcutaneous injection of ACP-001 | Drug: ACP-001<br>* Once weekly subcutaneous injection<br>|
| Experimental: ACP-001, dose-level 2<br>Once weekly subcutaneous injection of ACP-001 | Drug: ACP-001<br>* Once weekly subcutaneous injection<br>|
| Experimental: ACP-001, dose-level 3<br>Once weekly subcutaneous injection of ACP-001 | Drug: ACP-001<br>* Once weekly subcutaneous injection<br>|
| Active Comparator: Human Growth Hormone<br>Once daily subcutaneous injection of human Growth Hormone (rhGH) | Drug: Human Growth Hormone<br>* Once daily subcutaneous injection of human Growth Hormone<br>* Other names: Somatropin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Anti-hGH Binding Antibody Formation | Number of subjects with positive results for anti-hGH binding antibodies at two consecutive post-dose visits | Visit 2 - Visit 5 | 
| Incidence of Anti-hGH Neutralizing Antibody Formation | Number of subjects with positive results for anti-hGH neutralizing antibodies at two consecutive post-dose visits | Visit 2 - Visit 5 | 
| 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. | Start of study treatment through Visit 5 (Week 27) | 
| 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) | 0 hours to 168 hours 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) | 0 hours to 168 hours 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 | 0 hours to 168 hours at Visit 3 (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 | 0 hours to 168 hours at Visit 3 (Week 13) | 
| 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 | 0 hours to 168 hours at Visit 3 (Week 13) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Baseline to 6 months (Visit 5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Growth Hormone, rhGH, hGH, GHD