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)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Ascendis Pharma A/S
- Enrollment
- 53
- Locations
- 45
- Primary Endpoint
- Cmax of hGH
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 3 Years to 12 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
ACP-001, dose-level 2
Once weekly subcutaneous injection of ACP-001
Intervention: ACP-001 (Drug)
ACP-001, dose-level 3
Once weekly subcutaneous injection of ACP-001
Intervention: ACP-001 (Drug)
ACP-001, dose-level 1
Once weekly subcutaneous injection of ACP-001
Intervention: ACP-001 (Drug)
Human Growth Hormone
Once daily subcutaneous injection of human Growth Hormone (rhGH)
Intervention: Human Growth Hormone (Drug)
Outcomes
Primary Outcomes
Cmax of hGH
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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 13
E-Trough of IGF-1
Time Frame: 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 13
Emax of IGF-1
Time Frame: 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 Outcomes
- Annualized Height Velocity(Baseline to 6 months (Visit 5))