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

Phase 2

Completed

• Conditions: Adult Growth Hormone Deficiency
• Interventions: Drug: ACP-001 (TransCon hGH); Drug: Omnitrope

• Registration Number: NCT01247675
• Lead Sponsor: Ascendis Pharma A/S

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2010-11-23
• Study First Submitted QC: 2010-11-23
• Study First Posted: 2010-11-24
• Primary Completion: 2011-05
• Study Completion: 2011-05
• Results First Submitted: 2016-11-03
• Status Verified: 2017-01
• Results First Submitted QC: 2017-01-20
• Last Update Submitted: 2017-01-20
• Results First Posted: 2017-03-09
• Last Update Posted: 2017-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACP-001, 0.02 mg hGH/kg/wk	ACP-001 (TransCon hGH)	Once weekly subcutaneous injection of ACP-001 equivalent to 0.02 mg hGH/kg/week for 4 weeks
ACP-001, 0.08 mg hGH/kg/wk	ACP-001 (TransCon hGH)	Once weekly subcutaneous injection of ACP-001 equivalent to 0.08 mg hGH/kg/week for 4 weeks
ACP-001, 0.04 mg hGH/kg/wk	ACP-001 (TransCon hGH)	Once weekly subcutaneous injection of ACP-001 equivalent to 0.04 mg hGH/kg/week for 4 weeks
Omnitrope, 0.04 mg hGH/kg/wk	Omnitrope	Once daily subcutaneous injection of human Growth Hormone (Omnitrope) equivalent to 0.04 mg hGH/kg/week for 4 weeks

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (4)

Charité University Hospital Berlin; 🇩🇪 Berlin, Germany

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

University Hospital Genova; 🇮🇹 Genova, Italy