Adult Growth Hormone Deficiency
Conditions
Brief summary
This study investigates the safety, tolerability, pharmacokinetic profile (PK), and pharmacodynamic response (PD) of three different doses of ACP-001 given once-a-week compared to one dose-level of an approved daily human growth hormone product over a period of 4 weeks (4 weekly administrations versus 28 daily administrations) in adults with Growth Hormone Deficiency.
Interventions
DRUGACP-001 (TransCon hGH)
s.c., weekly injection
DRUGOmnitrope
s.c., daily injection
Sponsors
Ascendis Pharma A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female between 20 to 70 years * Body Mass Index (BMI, kg/m2) of 19.0 to 36.0 kg/m2, both inclusive * Adult Growth Hormone Deficient (AHGD) patients with documented growth hormone deficiency as defined in the Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II (Consensus Guidelines 1998 and 2007) * Fertile females must agree to use appropriate contraceptive methods and have a negative pregnancy test at inclusion * GH replacement therapy for at least 3 months * Willing to maintain current activity level during the trial * Subjects are able and willing to provide written informed consent and authorization for protected health information disclosure in accordance with Good Clinical Practice (GCP)
Exclusion criteria
* History of hypersensitivity and/or idiosyncrasy to any of the test compounds or excipients employed in this study. * Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods. Reliable methods for women are orally administered hormonal contraceptives, surgical intervention (e.g. tubal ligation), intrauterine device (IUD) and sexual abstinence. * Active malignant disease or malignant disease within the last 5 years * Proliferative retinopathy judged by retina-photo within the last year * Heart insufficiency as judged by the investigator and/or NYHA 3 or greater (NYHA criteria for diagnosis of diseases of the heart, 1994) * Subjects with uncontrolled diabetes with an HbA1c above 8.0% and/or insulin treatment * Stable pituitary hormone replacement therapy for less than 3 months * Impaired liver function as judged by the investigator or hepatic transaminases \> 2 times the upper limit of normal * Impaired kidney function as judged by the investigator and/or creatinine clearance \<50 mL/min and/or serum creatinine \> 1.4 mg/dL * Participation in another interventional clinical study involving an investigational compound within 3 months prior to enrolment in this study or participation in another interventional clinical study involving an investigational compound during this study. * Subjects who are unable to comply with the requirements of the study or who in the opinion of the investigator should not participate in the study. * History or presence of alcohol abuse or drug abuse. * Patients with known history for, or presence of, anti-hGH and / or anti-PEG antibodies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator) | Start of study treatment through Week 4 | Assessment of local tolerability was performed by examining injection sites by the investigator during study visits, and on the basis of records in the Patient Diary. Assessments included erythema, swelling, or pain. |
| Incidence of Treatment Emergent Anti-hGH Binding Antibody Formation | Start of study treatment through Day 42 | Number of subjects with treatment emergent anti-hGH binding antibodies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of hGH | Days 22 to 29 | As part of the following endpoint: Pharmacokinetic (PK) profile of serum human Growth Hormone (hGH) from ACP-001 treated dose groups compared to the PK profile of hGH from the daily Omnitrope treated group. Cmax (maximum value of concentration) values at Week 4 |
| Emax of IGF-I | Days 22 to 29 | As part of the following endpoint: Pharmacodynamic (PD) response of serum Insulin-like Growth Factor-I (IGF-I) from ACP-001 treated dose groups compared to the PD response of IGF-I from the daily Omnitrope treated group. Emax (maximum observed response) values at Week 4 |
Countries
Denmark, Germany, Italy, Sweden
Contacts
STUDY_DIRECTORMedical Director, MD
Ascendis Pharma A/S
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ACP-001, 0.02 mg hGH/kg/wk ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.02 mg hGH/kg/wk for 4 weeks | 10 |
| ACP-001, 0.04 mg hGH/kg/wk ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.04 mg hGH/kg/wk for 4 weeks | 10 |
| ACP-001, 0.08 mg hGH/kg/wk ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.08 mg hGH/kg/wk for 4 weeks | 9 |
| Omnitrope, 0.04 mg hGH/kg/wk Human Growth Hormone: s.c., daily injection equivalent to 0.04 mg hGH/kg/wk for 4 weeks | 8 |
| Total | 37 |
Baseline characteristics
| Characteristic | ACP-001, 0.02 mg hGH/kg/wk | ACP-001, 0.04 mg hGH/kg/wk | ACP-001, 0.08 mg hGH/kg/wk | Omnitrope, 0.04 mg hGH/kg/wk | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 12.6 | 45.9 years STANDARD_DEVIATION 15 | 51.6 years STANDARD_DEVIATION 18.1 | 44.0 years STANDARD_DEVIATION 15.7 | 49.5 years STANDARD_DEVIATION 15.4 |
| Body Mass Index | 27.6 kg/m² STANDARD_DEVIATION 4.4 | 27.9 kg/m² STANDARD_DEVIATION 4.4 | 30.7 kg/m² STANDARD_DEVIATION 4.4 | 25.7 kg/m² STANDARD_DEVIATION 4.4 | 28.0 kg/m² STANDARD_DEVIATION 4.6 |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 5 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 4 Participants | 5 Participants | 18 Participants |
| Weight | 82.3 kg STANDARD_DEVIATION 19.8 | 79.6 kg STANDARD_DEVIATION 17 | 92.5 kg STANDARD_DEVIATION 20.5 | 74.7 kg STANDARD_DEVIATION 16.6 | 82.4 kg STANDARD_DEVIATION 18.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 6 / 10 | 9 / 10 | 7 / 9 | 7 / 8 |
| serious Total, serious adverse events | 1 / 10 | 0 / 10 | 0 / 9 | 0 / 8 |
Outcome results
Primary
Incidence of Treatment Emergent Anti-hGH Binding Antibody Formation
Number of subjects with treatment emergent anti-hGH binding antibodies
Time frame: Start of study treatment through Day 42
Population: All patients who were randomized and received at least one dose of test product were included in the Safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ACP-001, 0.02 mg hGH/kg/wk | Incidence of Treatment Emergent Anti-hGH Binding Antibody Formation | 0 Participants |
| ACP-001, 0.04 mg hGH/kg/wk | Incidence of Treatment Emergent Anti-hGH Binding Antibody Formation | 0 Participants |
| ACP-001, 0.08 mg hGH/kg/wk | Incidence of Treatment Emergent Anti-hGH Binding Antibody Formation | 0 Participants |
| Omnitrope, 0.04 mg hGH/kg/wk | Incidence of Treatment Emergent Anti-hGH Binding Antibody Formation | 0 Participants |
Primary
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 records in the Patient Diary. Assessments included erythema, swelling, or pain.
Time frame: Start of study treatment through Week 4
Population: All patients who were randomized and received at least one dose of test product were included in the Safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ACP-001, 0.02 mg hGH/kg/wk | Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator) | 3 Number of subjects with any symptom |
| ACP-001, 0.04 mg hGH/kg/wk | Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator) | 3 Number of subjects with any symptom |
| ACP-001, 0.08 mg hGH/kg/wk | Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator) | 2 Number of subjects with any symptom |
| Omnitrope, 0.04 mg hGH/kg/wk | Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator) | 1 Number of subjects with any symptom |
Secondary
Cmax of hGH
As part of the following endpoint: Pharmacokinetic (PK) profile of serum human Growth Hormone (hGH) from ACP-001 treated dose groups compared to the PK profile of hGH from the daily Omnitrope treated group. Cmax (maximum value of concentration) values at Week 4
Time frame: Days 22 to 29
Population: Pharmacokinetic and pharmacodynamic analysis was performed on all patients who had at least one measurement of the primary variable and who had attended the Day 28 study visit. Two patients in Cohort 2 (ACP-001, 0.04 mg hGH/kg/wk) were withdrawn from the study before Day 28 and were therefore excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACP-001, 0.02 mg hGH/kg/wk | Cmax of hGH | 1.2 ng/mL | Standard Deviation 0.8 |
| ACP-001, 0.04 mg hGH/kg/wk | Cmax of hGH | 1.9 ng/mL | Standard Deviation 0.9 |
| ACP-001, 0.08 mg hGH/kg/wk | Cmax of hGH | 3.8 ng/mL | Standard Deviation 2 |
| Omnitrope, 0.04 mg hGH/kg/wk | Cmax of hGH | 2.0 ng/mL | Standard Deviation 1.1 |
Secondary
Emax of IGF-I
As part of the following endpoint: Pharmacodynamic (PD) response of serum Insulin-like Growth Factor-I (IGF-I) from ACP-001 treated dose groups compared to the PD response of IGF-I from the daily Omnitrope treated group. Emax (maximum observed response) values at Week 4
Time frame: Days 22 to 29
Population: Pharmacokinetic and pharmacodynamic analysis was performed on all patients who had at least one measurement of the primary variable and who had attended the Day 28 study visit. Two patients in Cohort 2 (ACP-001, 0.04 mg hGH/kg/wk) were withdrawn from the study before Day 28 and were therefore excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACP-001, 0.02 mg hGH/kg/wk | Emax of IGF-I | 71.8 ng/mL | Standard Deviation 26.9 |
| ACP-001, 0.04 mg hGH/kg/wk | Emax of IGF-I | 108.6 ng/mL | Standard Deviation 91.7 |
| ACP-001, 0.08 mg hGH/kg/wk | Emax of IGF-I | 125.6 ng/mL | Standard Deviation 70.1 |
| Omnitrope, 0.04 mg hGH/kg/wk | Emax of IGF-I | 109.8 ng/mL | Standard Deviation 37.1 |