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

Phase 2

Completed

• Conditions: Growth Hormone Deficiency (GHD)
• Interventions: Drug: ACP-001; Drug: Human Growth Hormone

• Registration Number: NCT01947907
• Lead Sponsor: Ascendis Pharma A/S

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-06-03
• Study Start: 2013-07
• Study First Submitted QC: 2013-09-18
• Study First Posted: 2013-09-23
• Primary Completion: 2015-07
• Study Completion: 2015-09
• Results First Submitted: 2016-10-03
• Status Verified: 2016-11
• Results First Submitted QC: 2016-11-28
• Last Update Submitted: 2016-11-28
• Results First Posted: 2017-01-19
• Last Update Posted: 2017-01-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACP-001, dose-level 1	ACP-001	Once weekly subcutaneous injection of ACP-001
ACP-001, dose-level 2	ACP-001	Once weekly subcutaneous injection of ACP-001
ACP-001, dose-level 3	ACP-001	Once weekly subcutaneous injection of ACP-001
Human Growth Hormone	Human Growth Hormone	Once daily subcutaneous injection of human Growth Hormone (rhGH)

Primary Outcome Measures

Name	Time	Method
Cmax of hGH	0 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)
Incidence of Anti-hGH Binding Antibody Formation	Visit 2 - Visit 5	Number of subjects with positive results for anti-hGH binding antibodies at two consecutive post-dose visits
Incidence of Anti-hGH Neutralizing Antibody Formation	Visit 2 - Visit 5	Number 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.
AUC0-168h of hGH	0 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)
AUEC0-168h of IGF-1	0 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
E-Trough of IGF-1	0 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-1	0 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 Outcome Measures

Name	Time	Method
Annualized Height Velocity	Baseline 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

Trial Locations

Locations (36)

Kharkiv National Medical University; 🇺🇦 Kharkiv, Ukraine

Institute of Endocrinology and Metabolism; 🇺🇦 Kiev, Ukraine

Donetsk Regional Children Clinical Hospital; 🇺🇦 Donetsk, Ukraine

Odessa National Medical University; 🇺🇦 Odessa, Ukraine

St. Spiridon County Clinic Emergency Hospital; 🇷🇴 Iasi, Romania

Masaryk´s Hospital; 🇨🇿 Ústí nad Labem, Czech Republic

Children's University Hospital; 🇸🇮 Ljubljana, Slovenia

Louis Turcanu Emergency Hospital for Children Timisoara; 🇷🇴 Timisoara, Romania

Emergency Clinical Hospital Cluj-Napoca; 🇷🇴 Cluj- Napoca, Romania

Children's Hospital of Athens "P. A. Kyriakou"; 🇬🇷 Athens, Greece

Ain Shams University Hospital; 🇪🇬 Cairo, Egypt

Cairo University Hospital; 🇪🇬 Cairo, Egypt

2nd Children City Clinic; 🇧🇾 Minsk, Belarus

University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Marina"; 🇧🇬 Varna, Bulgaria

El Mansoura University Hospital; 🇪🇬 El Mansoura, Egypt

University Hospital Leipzig; 🇩🇪 Leipzig, Germany

Hôpital des enfants Pellegrin; 🇫🇷 Bordeaux, France

Heim Pal Children's Hospital; 🇭🇺 Budapest, Hungary

Hôpital Jeanne de Flandre; 🇫🇷 Lille, France

Medical University of Lublin; 🇵🇱 Lublin, Poland

St. Petersburg State Pediatric Medical Academy; 🇷🇺 St. Petersburg, Russian Federation

Ankara University School of Medicine; 🇹🇷 Ankara, Turkey

Ukrainian Children Specialized Clinical Hospital; 🇺🇦 Kiev, Ukraine

Hôpital Femme-Mère-Enfant; 🇫🇷 Lyon, France

El Shatby University Hospital; 🇪🇬 Alexandria, Egypt

University of Szeged; 🇭🇺 Szeged, Hungary

University of Pecs; 🇭🇺 Pecs, Hungary

Regional Hospital N°2 Rzeszow; 🇵🇱 Rzeszów, Poland

Children's Memorial Health Institute Warsaw; 🇵🇱 Warsaw, Poland

Ege Üniversity; 🇹🇷 Izmir, Turkey

Federal State Budgetary Institution; 🇷🇺 Moscow, Russian Federation

Samara State Medical University; 🇷🇺 Samara, Russian Federation

Bashkir State Medical University; 🇷🇺 Ufa, Russian Federation

Buda Children's Hospital; 🇭🇺 Budapest, Hungary

University Children's Hospital Magdeburg; 🇩🇪 Magdeburg, Germany

University Medical Hospital; 🇵🇱 Katowice, Poland