A Safety, Pharmacokinetic and Pharmacodynamic Study of ACP-001 (TransCon hGH) in Adults With Growth Hormone Deficiency

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Multiple Dose, Open-Label, Parallel-Group, Active Controlled, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ACP-001 in Adult Patients With Growth Hormone Deficiency

Conditions
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Adult Growth Hormone Deficiency

Intervention / Treatment
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* Drug: ACP-001 (TransCon hGH)
* Drug: ACP-001 (TransCon hGH)
* Drug: ACP-001 (TransCon hGH)
* Drug: Omnitrope


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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, 0.02 mg hGH/kg/wk<br>Once weekly subcutaneous injection of ACP-001 equivalent to 0.02 mg hGH/kg/week for 4 weeks | Drug: ACP-001 (TransCon hGH)<br>* s.c., weekly injection<br>|
| Experimental: ACP-001, 0.04 mg hGH/kg/wk<br>Once weekly subcutaneous injection of ACP-001 equivalent to 0.04 mg hGH/kg/week for 4 weeks | Drug: ACP-001 (TransCon hGH)<br>* s.c., weekly injection<br>|
| Experimental: ACP-001, 0.08 mg hGH/kg/wk<br>Once weekly subcutaneous injection of ACP-001 equivalent to 0.08 mg hGH/kg/week for 4 weeks | Drug: ACP-001 (TransCon hGH)<br>* s.c., weekly injection<br>|
| Active Comparator: Omnitrope, 0.04 mg hGH/kg/wk<br>Once daily subcutaneous injection of human Growth Hormone (Omnitrope) equivalent to 0.04 mg hGH/kg/week for 4 weeks | Drug: Omnitrope<br>* s.c., daily injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Start of study treatment through Week 4 | 
| Incidence of Treatment Emergent Anti-hGH Binding Antibody Formation | Number of subjects with treatment emergent anti-hGH binding antibodies | Start of study treatment through Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Days 22 to 29 | 
| 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 | Days 22 to 29 |