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Safety, PK/PD (Pharmacokinetics/Pharmacodynamics) and Efficacy of ACP-001 Weekly Versus Daily hGH in Children With Growth Hormone Deficiency (GHD)

A Multicenter, Phase 2, Randomized, Open Label, Active-controlled, Parallel-group Study Investigating the Safety, Tolerability, and Efficacy of Different Dose Levels of ACP-001 Administered Once Weekly Versus Standard Daily rhGH Replacement Therapy in Pre-pubertal Children With Growth Hormone Deficiency (GHD)

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01947907
Enrollment
53
Registered
2013-09-23
Start date
2013-07-31
Completion date
2015-09-30
Last updated
2017-01-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Growth Hormone Deficiency (GHD)

Keywords

Human Growth Hormone, rhGH, hGH, GHD

Brief summary

A six month study of ACP-001, a long-acting growth hormone product, versus standard human growth hormone therapy. ACP-001 will be given once-a-week, standard human growth hormone (hGH) will be given on a daily basis. The primary aim is to demonstrate safety, pharmacokinetics and pharmacodynamics over a period of six months. A secondary objective is the comparison of height velocity (HV) of the ACP-001 treated groups to the daily hGH treatment group.

Interventions

DRUGACP-001

Once weekly subcutaneous injection

DRUGHuman Growth Hormone

Once daily subcutaneous injection of human Growth Hormone

Sponsors

Ascendis Pharma A/S
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No

Inclusion criteria

* Prepubertal children, Tanner stage 1 * Diagnosis of GHD, confirmed by two stimulation tests * Bone age not greater than chronological age * Impaired height and height velocity * BMI within +/- 2 SD (standard deviations) * Baseline IGF-1 (insulin-like growth factor) * Normal fundoscopy * Stable hormonal replacement therapy (other than hGH) * Written Informed Consent

Exclusion criteria

* Prior exposure to rhGH or IGF-I * Past or present intracranial tumor; history or presence of malignant disease * Small for gestational age (SGA) * Malnutrition * Psychosocial dwarfism * Coeliac disease * Anti-hGH antibodies * Diabetes mellitus * Chromosomal abnormalities (e.g. Turner syndrome, SHOX) * Closed epiphyses * Known or suspected HIV infection

Design outcomes

Primary

MeasureTime frameDescription
AUEC0-168h of IGF-10 hours to 168 hours at Visit 3 (Week 13)As part of the following endpoint: PD profile of serum IGF-1 during V1 and V3 compared between the ACP-001 dose groups and to the rhGH group. Uncorrected AUEC0-168 (area under the efficacy curve from 0h-168h) values at Week 13
Incidence of Anti-hGH Binding Antibody FormationVisit 2 - Visit 5Number of subjects with positive results for anti-hGH binding antibodies at two consecutive post-dose visits
Incidence of Anti-hGH Neutralizing Antibody FormationVisit 2 - Visit 5Number of subjects with positive results for anti-hGH neutralizing antibodies at two consecutive post-dose visits
Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)Start of study treatment through Visit 5 (Week 27)Assessment of local tolerability was performed by examining injection sites (by the investigator during study visits) and on the basis of anamnestic data and records in the Patient Diary. Assessments included pain, redness, bruising, swelling, and itching. Every subject was counted only once within each symptom category.
Cmax of hGH0 hours to 168 hours at Visit 3 (Week 13)As part of the following endpoint: PK profile of serum hGH from ACP-001 treated patients compared between ACP-001 dose groups and to the pharmacokinetic (PK) profile of hGH from the daily rhGH groups during visit 1 and 3. Uncorrected Cmax (maximum value of concentration) values at Visit 3 (Week 13)
AUC0-168h of hGH0 hours to 168 hours at Visit 3 (Week 13)As part of the following endpoint: PK profile of serum hGH from ACP-001 treated patients compared between ACP-001 dose groups and to the PK profile of hGH from the daily rhGH group during Visit 1 and Visit 3 Uncorrected AUC0-168h (area under the curve from 0h to 168h) values at Visit 3 (Week 13)
E-Trough of IGF-10 hours to 168 hours at Visit 3 (Week 13)As part of the following endpoint: PD profile of serum IGF-1 during Visit 1 and Visit 3 compared between the ACP-001 dose groups and to the daily rhGH group Uncorrected E-Trough (the pre-dose efficacy response) values at Week 13
Emax of IGF-10 hours to 168 hours at Visit 3 (Week 13)As part of the following endpoint: PD profile of serum IGF-1 during V1 and V3 compared between the ACP-001 dose groups and to the daily rhGH group

Secondary

MeasureTime frameDescription
Annualized Height VelocityBaseline to 6 months (Visit 5)Annualized HV during treatment with ACP-001 or daily rhGH at the end of 6 months, for each ACP-001 dose group and for the daily rhGH dose group

Countries

Belarus, Bulgaria, Czechia, Egypt, France, Germany, Greece, Hungary, Poland, Romania, Russia, Slovenia, Turkey (Türkiye), Ukraine

Participant flow

Participants by arm

ArmCount
ACP-001, Dose-level 1
Once weekly subcutaneous injection of ACP-001 ACP-001: Once weekly subcutaneous injection
12
ACP-001, Dose-level 2
Once weekly subcutaneous injection of ACP-001 ACP-001: Once weekly subcutaneous injection
14
ACP-001, Dose-level 3
Once weekly subcutaneous injection of ACP-001 ACP-001: Once weekly subcutaneous injection
14
Human Growth Hormone
Once daily subcutaneous injection of human Growth Hormone (rhGH) Human Growth Hormone: Once daily subcutaneous injection of human Growth Hormone
13
Total53

Baseline characteristics

CharacteristicACP-001, Dose-level 2TotalHuman Growth HormoneACP-001, Dose-level 3ACP-001, Dose-level 1
Age, Categorical
<=18 years
14 Participants53 Participants13 Participants14 Participants12 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Continuous8.24 years
STANDARD_DEVIATION 2.13
7.77 years
STANDARD_DEVIATION 2.57
7.53 years
STANDARD_DEVIATION 2.483
7.32 years
STANDARD_DEVIATION 2.784
7.98 years
STANDARD_DEVIATION 2.889
Baseline Height SDS-2.75 Standard Deviation Score
STANDARD_DEVIATION 0.383
-3.06 Standard Deviation Score
STANDARD_DEVIATION 0.905
-3.27 Standard Deviation Score
STANDARD_DEVIATION 1.077
-3.17 Standard Deviation Score
STANDARD_DEVIATION 1.04
-3.05 Standard Deviation Score
STANDARD_DEVIATION 1.127
Baseline IGF-1 SDS (standard deviation score)-2.017 Standard Deviation Score
STANDARD_DEVIATION 0.7713
-2.19 Standard Deviation Score
STANDARD_DEVIATION 0.782
-2.502 Standard Deviation Score
STANDARD_DEVIATION 0.896
-2.19 Standard Deviation Score
STANDARD_DEVIATION 0.7169
-2.034 Standard Deviation Score
STANDARD_DEVIATION 0.7429
Gender
Female
4 Participants15 Participants3 Participants5 Participants3 Participants
Gender
Male
10 Participants38 Participants10 Participants9 Participants9 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
14 Participants53 Participants13 Participants14 Participants12 Participants
Region of Enrollment
Belarus
2 participants7 participants1 participants2 participants2 participants
Region of Enrollment
Bulgaria
0 participants1 participants1 participants0 participants0 participants
Region of Enrollment
Egypt
4 participants7 participants1 participants0 participants2 participants
Region of Enrollment
Greece
0 participants3 participants0 participants2 participants1 participants
Region of Enrollment
Hungary
0 participants1 participants0 participants1 participants0 participants
Region of Enrollment
Poland
0 participants1 participants0 participants1 participants0 participants
Region of Enrollment
Romania
0 participants2 participants1 participants0 participants1 participants
Region of Enrollment
Russian Federation
4 participants21 participants6 participants7 participants4 participants
Region of Enrollment
Turkey
0 participants3 participants2 participants0 participants1 participants
Region of Enrollment
Ukraine
4 participants7 participants1 participants1 participants1 participants
Screening Peak GH Values5.16 ng/mL
STANDARD_DEVIATION 2.598
4.95 ng/mL
STANDARD_DEVIATION 2.829
5.15 ng/mL
STANDARD_DEVIATION 3.068
4.44 ng/mL
STANDARD_DEVIATION 2.77
5.09 ng/mL
STANDARD_DEVIATION 3.169

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —
other
Total, other adverse events
7 / 126 / 148 / 148 / 13
serious
Total, serious adverse events
1 / 120 / 140 / 140 / 13

Outcome results

Primary

AUC0-168h of hGH

As part of the following endpoint: PK profile of serum hGH from ACP-001 treated patients compared between ACP-001 dose groups and to the PK profile of hGH from the daily rhGH group during Visit 1 and Visit 3 Uncorrected AUC0-168h (area under the curve from 0h to 168h) values at Visit 3 (Week 13)

Time frame: 0 hours to 168 hours at Visit 3 (Week 13)

ArmMeasureValue (MEAN)Dispersion
ACP-001, Dose-level 1AUC0-168h of hGH696.34 h*ng/mLStandard Deviation 410.096
ACP-001, Dose-level 2AUC0-168h of hGH787.41 h*ng/mLStandard Deviation 483.169
ACP-001, Dose-level 3AUC0-168h of hGH2167.43 h*ng/mLStandard Deviation 1064.729
Human Growth HormoneAUC0-168h of hGH556.88 h*ng/mLStandard Deviation 412.618
Primary

AUEC0-168h of IGF-1

As part of the following endpoint: PD profile of serum IGF-1 during V1 and V3 compared between the ACP-001 dose groups and to the rhGH group. Uncorrected AUEC0-168 (area under the efficacy curve from 0h-168h) values at Week 13

Time frame: 0 hours to 168 hours at Visit 3 (Week 13)

ArmMeasureValue (MEAN)Dispersion
ACP-001, Dose-level 1AUEC0-168h of IGF-128526.19 h*ng/mLStandard Deviation 15756.44
ACP-001, Dose-level 2AUEC0-168h of IGF-135591.94 h*ng/mLStandard Deviation 17068.59
ACP-001, Dose-level 3AUEC0-168h of IGF-136066.01 h*ng/mLStandard Deviation 17379.44
Primary

Cmax of hGH

As part of the following endpoint: PK profile of serum hGH from ACP-001 treated patients compared between ACP-001 dose groups and to the pharmacokinetic (PK) profile of hGH from the daily rhGH groups during visit 1 and 3. Uncorrected Cmax (maximum value of concentration) values at Visit 3 (Week 13)

Time frame: 0 hours to 168 hours at Visit 3 (Week 13)

ArmMeasureValue (MEAN)Dispersion
ACP-001, Dose-level 1Cmax of hGH12.558 ng/mLStandard Deviation 8.678
ACP-001, Dose-level 2Cmax of hGH13.418 ng/mLStandard Deviation 9.428
ACP-001, Dose-level 3Cmax of hGH31.8 ng/mLStandard Deviation 17.499
Human Growth HormoneCmax of hGH16.612 ng/mLStandard Deviation 12.777
Primary

Emax of IGF-1

As part of the following endpoint: PD profile of serum IGF-1 during V1 and V3 compared between the ACP-001 dose groups and to the daily rhGH group

Time frame: 0 hours to 168 hours at Visit 3 (Week 13)

ArmMeasureValue (MEAN)Dispersion
ACP-001, Dose-level 1Emax of IGF-1209.5 ng/mLStandard Deviation 120.189
ACP-001, Dose-level 2Emax of IGF-1276 ng/mLStandard Deviation 126.632
ACP-001, Dose-level 3Emax of IGF-1289.92 ng/mLStandard Deviation 129.469
Primary

E-Trough of IGF-1

As part of the following endpoint: PD profile of serum IGF-1 during Visit 1 and Visit 3 compared between the ACP-001 dose groups and to the daily rhGH group Uncorrected E-Trough (the pre-dose efficacy response) values at Week 13

Time frame: 0 hours to 168 hours at Visit 3 (Week 13)

ArmMeasureValue (MEAN)Dispersion
ACP-001, Dose-level 1E-Trough of IGF-197.17 ng/mLStandard Deviation 50.53
ACP-001, Dose-level 2E-Trough of IGF-1156 ng/mLStandard Deviation 76.235
ACP-001, Dose-level 3E-Trough of IGF-1167.83 ng/mLStandard Deviation 74.01
Primary

Incidence of Anti-hGH Binding Antibody Formation

Number of subjects with positive results for anti-hGH binding antibodies at two consecutive post-dose visits

Time frame: Visit 2 - Visit 5

Population: Safety analysis set includes all patients who receive at least one dose of planned study medication

ArmMeasureValue (NUMBER)
ACP-001, Dose-level 1Incidence of Anti-hGH Binding Antibody Formation1 participants
ACP-001, Dose-level 2Incidence of Anti-hGH Binding Antibody Formation0 participants
ACP-001, Dose-level 3Incidence of Anti-hGH Binding Antibody Formation0 participants
Human Growth HormoneIncidence of Anti-hGH Binding Antibody Formation0 participants
Primary

Incidence of Anti-hGH Neutralizing Antibody Formation

Number of subjects with positive results for anti-hGH neutralizing antibodies at two consecutive post-dose visits

Time frame: Visit 2 - Visit 5

ArmMeasureValue (NUMBER)
ACP-001, Dose-level 1Incidence of Anti-hGH Neutralizing Antibody Formation0 participants
ACP-001, Dose-level 2Incidence of Anti-hGH Neutralizing Antibody Formation0 participants
ACP-001, Dose-level 3Incidence of Anti-hGH Neutralizing Antibody Formation0 participants
Human Growth HormoneIncidence of Anti-hGH Neutralizing Antibody Formation0 participants
Primary

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 anamnestic data and records in the Patient Diary. Assessments included pain, redness, bruising, swelling, and itching. Every subject was counted only once within each symptom category.

Time frame: Start of study treatment through Visit 5 (Week 27)

ArmMeasureValue (NUMBER)
ACP-001, Dose-level 1Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)7 Number of subjects with any symptom
ACP-001, Dose-level 2Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)6 Number of subjects with any symptom
ACP-001, Dose-level 3Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)6 Number of subjects with any symptom
Human Growth HormoneNumber of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)6 Number of subjects with any symptom
Secondary

Annualized Height Velocity

Annualized HV during treatment with ACP-001 or daily rhGH at the end of 6 months, for each ACP-001 dose group and for the daily rhGH dose group

Time frame: Baseline to 6 months (Visit 5)

ArmMeasureValue (MEAN)Dispersion
ACP-001, Dose-level 1Annualized Height Velocity11.93 cm/yearStandard Deviation 4.066
ACP-001, Dose-level 2Annualized Height Velocity12.89 cm/yearStandard Deviation 3.464
ACP-001, Dose-level 3Annualized Height Velocity13.85 cm/yearStandard Deviation 4.009
Human Growth HormoneAnnualized Height Velocity11.64 cm/yearStandard Deviation 3.592

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026