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

• ClinicalTrials.gov Identifier: NCT01247675
• Recruitment Status: Completed
• First Posted: November 24, 2010
• Results First Posted: March 9, 2017
• Last Update Posted: March 9, 2017
• Sponsor: Ascendis Pharma A/S
• Information provided by (Responsible Party): Ascendis Pharma A/S

Tracking Information

• First Submitted Date: November 23, 2010
• First Posted Date: November 24, 2010
• Results First Submitted Date: November 3, 2016
• Results First Posted Date: March 9, 2017
• Last Update Posted Date: March 9, 2017
• Study Start Date: November 2010
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 20, 2017)

• Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator) [ Time Frame: 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 [ Time Frame: Start of study treatment through Day 42 ]
  Number of subjects with treatment emergent anti-hGH binding antibodies

Original Primary Outcome Measures (submitted: November 23, 2010)

Safety and Tolerability (Adverse events, vital signs, safety laboratory, immunogenicity) [ Time Frame: 4 weeks ]

Adverse events, vital signs, safety laboratory, immunogenicity

Current Secondary Outcome Measures (submitted: January 20, 2017)

• Cmax of hGH [ Time Frame: 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 [ Time Frame: 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

Original Secondary Outcome Measures (submitted: November 23, 2010)

• Change of IGF-I levels over time [ Time Frame: 4 weeks ]
  Change from baseline after wash-out phase
• Change of IGFBP-3 over time [ Time Frame: 4 weeks ]
  Change from baseline after wash-out phase

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Safety, Pharmacokinetic and Pharmacodynamic Study of ACP-001 (TransCon hGH) in Adults With Growth Hormone Deficiency
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Adult Growth Hormone Deficiency

Intervention

• Drug: ACP-001 (TransCon hGH)
  s.c., weekly injection
• Drug: Omnitrope
  s.c., daily injection

Study Arms

• 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
  Intervention: Drug: ACP-001 (TransCon hGH)
• 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
  Intervention: Drug: ACP-001 (TransCon hGH)
• 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
  Intervention: Drug: ACP-001 (TransCon hGH)
• 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
  Intervention: Drug: Omnitrope

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 2, 2013): 37
• Original Estimated Enrollment (submitted: November 23, 2010): 32
• Actual Study Completion Date: May 2011
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Germany, Italy, Sweden

Administrative Information

• NCT Number: NCT01247675
• Other Study ID Numbers: ACP-001 CT-002
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ascendis Pharma A/S
• Original Responsible Party: Michael Beckert, MD (CMO), Ascendis Pharma A/S
• Current Study Sponsor: Ascendis Pharma A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Ascendis Pharma A/S
• Verification Date: January 2017