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

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

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.

Study Overview

• Status: Completed
• Conditions: Adult Growth Hormone Deficiency
• Intervention / Treatment: Drug: ACP-001 (TransCon hGH); Drug: Omnitrope

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital
• Germany
  • Berlin, Germany, 12203
    • Charité University Hospital Berlin
• Italy
  • Genova, Italy, 16132
    • University Hospital Genova
• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACP-001, 0.02 mg hGH/kg/wk; Once weekly subcutaneous injection of ACP-001 equivalent to 0.02 mg hGH/kg/week for 4 weeks	Drug: ACP-001 (TransCon hGH); s.c., weekly injection
Experimental: ACP-001, 0.04 mg hGH/kg/wk; Once weekly subcutaneous injection of ACP-001 equivalent to 0.04 mg hGH/kg/week for 4 weeks	Drug: ACP-001 (TransCon hGH); s.c., weekly injection
Experimental: ACP-001, 0.08 mg hGH/kg/wk; Once weekly subcutaneous injection of ACP-001 equivalent to 0.08 mg hGH/kg/week for 4 weeks	Drug: ACP-001 (TransCon hGH); s.c., weekly injection
Active Comparator: Omnitrope, 0.04 mg hGH/kg/wk; Once daily subcutaneous injection of human Growth Hormone (Omnitrope) equivalent to 0.04 mg hGH/kg/week for 4 weeks	Drug: Omnitrope; s.c., daily injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ascendis Pharma A/S
• Investigators: Study Director: Michael Beckert, MD, Ascendis Pharma A/S

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: November 23, 2010
• First Submitted That Met QC Criteria: November 23, 2010
• First Posted (Estimate): November 24, 2010

Study Record Updates

• Last Update Posted (Actual): March 9, 2017
• Last Update Submitted That Met QC Criteria: January 20, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary; Endocrine System Diseases
• Other Study ID Numbers: ACP-001 CT-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No