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

November 28, 2016 updated by: Ascendis Pharma A/S

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belarus
      • Minsk, Belarus
        • 2nd Children City Clinic
  • Bulgaria
      • Varna, Bulgaria
        • University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Marina"
  • Czech Republic
      • Ústí nad Labem, Czech Republic
        • Masaryk´s Hospital
  • Egypt
      • Alexandria, Egypt
        • El Shatby University Hospital
      • Cairo, Egypt
        • Cairo University Hospital
      • Cairo, Egypt
        • Ain Shams University Hospital
      • El Mansoura, Egypt
        • El Mansoura University Hospital
  • France
      • Bordeaux, France
        • Hôpital des enfants Pellegrin
      • Lille, France
        • Hopital Jeanne de Flandre
      • Lyon, France
        • Hôpital Femme-Mère-Enfant
  • Germany
      • Leipzig, Germany
        • University Hospital Leipzig
      • Magdeburg, Germany
        • University Children's Hospital Magdeburg
  • Greece
      • Athens, Greece
        • Children's Hospital of Athens "P. A. Kyriakou"
  • Hungary
      • Budapest, Hungary
        • Buda Children's Hospital
      • Budapest, Hungary
        • Heim Pal Children's Hospital
      • Pecs, Hungary
        • University of Pecs
      • Szeged, Hungary
        • University of Szeged
  • Poland
      • Katowice, Poland
        • University Medical Hospital
      • Lublin, Poland
        • Medical University of Lublin
      • Rzeszów, Poland
        • Regional Hospital N°2 Rzeszow
      • Warsaw, Poland
        • Children's Memorial Health Institute Warsaw
  • Romania
      • Cluj- Napoca, Romania
        • Emergency Clinical Hospital Cluj-Napoca
      • Iasi, Romania
        • St. Spiridon County Clinic Emergency Hospital
      • Timisoara, Romania
        • Louis Turcanu Emergency Hospital for Children Timisoara
  • Russian Federation
      • Moscow, Russian Federation
        • Federal State Budgetary Institution
      • Samara, Russian Federation
        • Samara state medical university
      • St. Petersburg, Russian Federation
        • St. Petersburg State Pediatric Medical Academy
      • Ufa, Russian Federation
        • Bashkir State Medical University
  • Slovenia
      • Ljubljana, Slovenia
        • Children's University Hospital
  • Turkey
      • Ankara, Turkey
        • Ankara University School of Medicine
      • Izmir, Turkey
        • Ege University
  • Ukraine
      • Donetsk, Ukraine
        • Donetsk Regional Children Clinical Hospital
      • Kharkiv, Ukraine
        • Kharkiv National Medical University
      • Kiev, Ukraine
        • Institute of Endocrinology and Metabolism
      • Kiev, Ukraine
        • Ukrainian Children Specialized Clinical Hospital
      • Odessa, Ukraine
        • Odessa National Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ACP-001, dose-level 1
Once weekly subcutaneous injection of ACP-001
Drug: ACP-001
Once weekly subcutaneous injection
Experimental: ACP-001, dose-level 2
Once weekly subcutaneous injection of ACP-001
Drug: ACP-001
Once weekly subcutaneous injection
Experimental: ACP-001, dose-level 3
Once weekly subcutaneous injection of ACP-001
Drug: ACP-001
Once weekly subcutaneous injection
Active Comparator: Human Growth Hormone
Once daily subcutaneous injection of human Growth Hormone (rhGH)
Drug: Human Growth Hormone
Once daily subcutaneous injection of human Growth Hormone
Other Names:
  • Somatropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Anti-hGH Binding Antibody Formation
Time Frame: Visit 2 - Visit 5
Number of subjects with positive results for anti-hGH binding antibodies at two consecutive post-dose visits
Visit 2 - Visit 5
Incidence of Anti-hGH Neutralizing Antibody Formation
Time Frame: Visit 2 - Visit 5
Number of subjects with positive results for anti-hGH neutralizing antibodies at two consecutive post-dose visits
Visit 2 - Visit 5
Number of Subjects Reporting Local Tolerability Events (Assessed by the Patient and Investigator)
Time Frame: 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.
Start of study treatment through Visit 5 (Week 27)
Cmax of hGH
Time Frame: 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)
0 hours to 168 hours at Visit 3 (Week 13)
AUC0-168h of hGH
Time Frame: 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)
0 hours to 168 hours at Visit 3 (Week 13)
E-Trough of IGF-1
Time Frame: 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
0 hours to 168 hours at Visit 3 (Week 13)
Emax of IGF-1
Time Frame: 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
0 hours to 168 hours at Visit 3 (Week 13)
AUEC0-168h of IGF-1
Time Frame: 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
0 hours to 168 hours at Visit 3 (Week 13)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized Height Velocity
Time Frame: 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
Baseline to 6 months (Visit 5)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ascendis Pharma A/S

Investigators

  • Study Director: Michael Beckert, MD, Ascendis Pharma A/S
  • Principal Investigator: Pierre Chatelain, Prof, MD, University of Lyon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2013

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

September 1, 2015

Study Registration Dates

First Submitted

June 3, 2013

First Submitted That Met QC Criteria

September 18, 2013

First Posted (Estimate)

September 23, 2013

Study Record Updates

Last Update Posted (Estimate)

January 19, 2017

Last Update Submitted That Met QC Criteria

November 28, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACP-001_CT-004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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