Trial Outcomes & Findings for A Safety, Pharmacokinetic and Pharmacodynamic Study of ACP-001 (TransCon hGH) in Adults With Growth Hormone Deficiency (NCT NCT01247675)

Last Updated: 2017-03-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

37 participants

Primary outcome timeframe

Start of study treatment through Week 4

Results posted on

2017-03-09

Participant Flow

Participant milestones

Participant milestones
Measure	ACP-001, 0.04 mg hGH/kg/wk ACP-001 (TransCon hGH): subcutaneous, weekly injection equivalent to 0.04 mg hGH/kg/wk over 4 weeks. Prior to randomization, study subjects entered a 14 to 21 day wash out period following cessation of daily growth hormone therapy.	ACP-001, 0.08 mg hGH/kg/wk ACP-001 (TransCon hGH): subcutaneous, weekly injection equivalent to 0.08 mg hGH/kg/wk over 4 weeks. Prior to randomization, study subjects entered a 14 to 21 day wash out period following cessation of daily growth hormone therapy.	Omnitrope, 0.04 mg hGH/kg/wk Human Growth Hormone: subcutaneous, daily injection of Omnitrope equivalent to 0.04 mg/kg/wk over 4 weeks. Prior to randomization, study subjects entered a wash out period of 14 to 21 days following cessation of daily growth hormone therapy.	ACP-001, 0.02 mg hGH/kg/wk ACP-001 (TransCon hGH): subcutaneous, weekly injection equivalent to 0.02 mg hGH/kg/wk over 4 weeks. Prior to randomization, study subjects entered a 14 to 21 day wash out period following cessation of daily growth hormone therapy.
Overall Study STARTED	10	9	8	10
Overall Study COMPLETED	8	9	8	8
Overall Study NOT COMPLETED	2	0	0	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ACP-001, 0.02 mg hGH/kg/wk n=10 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.02 mg hGH/kg/wk for 4 weeks	ACP-001, 0.04 mg hGH/kg/wk n=10 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.04 mg hGH/kg/wk for 4 weeks	ACP-001, 0.08 mg hGH/kg/wk n=9 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.08 mg hGH/kg/wk for 4 weeks	Omnitrope, 0.04 mg hGH/kg/wk n=8 Participants Human Growth Hormone: s.c., daily injection equivalent to 0.04 mg hGH/kg/wk for 4 weeks	Total n=37 Participants Total of all reporting groups
Age, Continuous	55.7 years STANDARD_DEVIATION 12.6 • n=5 Participants	45.9 years STANDARD_DEVIATION 15.0 • n=7 Participants	51.6 years STANDARD_DEVIATION 18.1 • n=5 Participants	44.0 years STANDARD_DEVIATION 15.7 • n=4 Participants	49.5 years STANDARD_DEVIATION 15.4 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	19 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	18 Participants n=21 Participants
Weight	82.3 kg STANDARD_DEVIATION 19.8 • n=5 Participants	79.6 kg STANDARD_DEVIATION 17.0 • n=7 Participants	92.5 kg STANDARD_DEVIATION 20.5 • n=5 Participants	74.7 kg STANDARD_DEVIATION 16.6 • n=4 Participants	82.4 kg STANDARD_DEVIATION 18.9 • n=21 Participants
Body Mass Index	27.6 kg/m² STANDARD_DEVIATION 4.4 • n=5 Participants	27.9 kg/m² STANDARD_DEVIATION 4.4 • n=7 Participants	30.7 kg/m² STANDARD_DEVIATION 4.4 • n=5 Participants	25.7 kg/m² STANDARD_DEVIATION 4.4 • n=4 Participants	28.0 kg/m² STANDARD_DEVIATION 4.6 • n=21 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	ACP-001, 0.02 mg hGH/kg/wk n=10 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.02 mg hGH/kg/wk for 4 weeks	ACP-001, 0.04 mg hGH/kg/wk n=10 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.04 mg hGH/kg/wk for 4 weeks	ACP-001, 0.08 mg hGH/kg/wk n=9 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.08 mg hGH/kg/wk for 4 weeks	Omnitrope, 0.04 mg hGH/kg/wk n=8 Participants Human Growth Hormone: s.c., daily injection of Omnitrope equivalent to 0.04 mg hGH/kg/wk for 4 weeks
Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)	3 Number of subjects with any symptom	3 Number of subjects with any symptom	2 Number of subjects with any symptom	1 Number of subjects with any symptom

PRIMARY outcome

Timeframe: 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.

Number of subjects with treatment emergent anti-hGH binding antibodies

Outcome measures

Outcome measures
Measure	ACP-001, 0.02 mg hGH/kg/wk n=10 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.02 mg hGH/kg/wk for 4 weeks	ACP-001, 0.04 mg hGH/kg/wk n=10 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.04 mg hGH/kg/wk for 4 weeks	ACP-001, 0.08 mg hGH/kg/wk n=9 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.08 mg hGH/kg/wk for 4 weeks	Omnitrope, 0.04 mg hGH/kg/wk n=8 Participants Human Growth Hormone: s.c., daily injection of Omnitrope equivalent to 0.04 mg hGH/kg/wk for 4 weeks
Incidence of Treatment Emergent Anti-hGH Binding Antibody Formation	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	ACP-001, 0.02 mg hGH/kg/wk n=10 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.02 mg hGH/kg/wk for 4 weeks	ACP-001, 0.04 mg hGH/kg/wk n=8 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.04 mg hGH/kg/wk for 4 weeks	ACP-001, 0.08 mg hGH/kg/wk n=9 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.08 mg hGH/kg/wk for 4 weeks	Omnitrope, 0.04 mg hGH/kg/wk n=8 Participants Human Growth Hormone: s.c., daily injection of Omnitrope equivalent to 0.04 mg hGH/kg/wk for 4 weeks
Cmax of hGH	1.2 ng/mL Standard Deviation 0.8	1.9 ng/mL Standard Deviation 0.9	3.8 ng/mL Standard Deviation 2.0	2.0 ng/mL Standard Deviation 1.1

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	ACP-001, 0.02 mg hGH/kg/wk n=10 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.02 mg hGH/kg/wk for 4 weeks	ACP-001, 0.04 mg hGH/kg/wk n=8 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.04 mg hGH/kg/wk for 4 weeks	ACP-001, 0.08 mg hGH/kg/wk n=9 Participants ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.08 mg hGH/kg/wk for 4 weeks	Omnitrope, 0.04 mg hGH/kg/wk n=8 Participants Human Growth Hormone: s.c., daily injection of Omnitrope equivalent to 0.04 mg hGH/kg/wk for 4 weeks
Emax of IGF-I	71.8 ng/mL Standard Deviation 26.9	108.6 ng/mL Standard Deviation 91.7	125.6 ng/mL Standard Deviation 70.1	109.8 ng/mL Standard Deviation 37.1

Adverse Events

ACP-001, 0.02 mg hGH/kg/wk

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

ACP-001, 0.04 mg hGH/kg/wk

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

ACP-001, 0.08 mg hGH/kg/wk

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Omnitrope, 0.04 mg hGH/kg/wk

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ACP-001, 0.02 mg hGH/kg/wk n=10 participants at risk ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.02 mg hGH/kg/wk for 4 weeks	ACP-001, 0.04 mg hGH/kg/wk n=10 participants at risk ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.04 mg hGH/kg/wk for 4 weeks	ACP-001, 0.08 mg hGH/kg/wk n=9 participants at risk ACP-001 (TransCon hGH): s.c., weekly injection equivalent to 0.08 mg hGH/kg/wk	Omnitrope, 0.04 mg hGH/kg/wk n=8 participants at risk Human Growth Hormone: s.c., daily injection of Omnitrope equivalent to 0.04 mg hGH/kg/wk for 4 weeks
Endocrine disorders Severe Adrenal Crisis	10.0% 1/10 • Number of events 1 • Reported Adverse Events include events starting on or after Day 0 and ending on or before Day 42. A subject with more than one finding in a specific category was only counted once.	0.00% 0/10 • Reported Adverse Events include events starting on or after Day 0 and ending on or before Day 42. A subject with more than one finding in a specific category was only counted once.	0.00% 0/9 • Reported Adverse Events include events starting on or after Day 0 and ending on or before Day 42. A subject with more than one finding in a specific category was only counted once.	0.00% 0/8 • Reported Adverse Events include events starting on or after Day 0 and ending on or before Day 42. A subject with more than one finding in a specific category was only counted once.
Respiratory, thoracic and mediastinal disorders Pleuritic Pain	10.0% 1/10 • Number of events 1 • Reported Adverse Events include events starting on or after Day 0 and ending on or before Day 42. A subject with more than one finding in a specific category was only counted once.	0.00% 0/10 • Reported Adverse Events include events starting on or after Day 0 and ending on or before Day 42. A subject with more than one finding in a specific category was only counted once.	0.00% 0/9 • Reported Adverse Events include events starting on or after Day 0 and ending on or before Day 42. A subject with more than one finding in a specific category was only counted once.	0.00% 0/8 • Reported Adverse Events include events starting on or after Day 0 and ending on or before Day 42. A subject with more than one finding in a specific category was only counted once.

Other adverse events

Additional Information

Michael Beckert, MD

Ascendis Pharma A/S

Phone: (+49) 172-155-2596

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER