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

NCT01947907 | Completed Phase 2 Results DMC

• 1 other identifier: ACP-001_CT-004
• Study Type: interventional
• Target: 53
• Locations: 14 countries
• Sites: 36

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.

Conditions

Growth Hormone Deficiency (GHD)

Keywords

Human Growth Hormone; rhGH; hGH; GHD

Outcome Measures

Primary Outcomes (8)

• Incidence of Anti-hGH Binding Antibody Formation

  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

  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)

  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

  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

  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

  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

  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

  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 Outcomes (1)

• Annualized Height Velocity

  Baseline to 6 months (Visit 5)

Study Arms (4)

ACP-001, dose-level 1

EXPERIMENTAL

Once weekly subcutaneous injection of ACP-001

Drug: ACP-001

ACP-001, dose-level 2

EXPERIMENTAL

Once weekly subcutaneous injection of ACP-001

Drug: ACP-001

ACP-001, dose-level 3

EXPERIMENTAL

Once weekly subcutaneous injection of ACP-001

Drug: ACP-001

Human Growth Hormone

ACTIVE COMPARATOR

Once daily subcutaneous injection of human Growth Hormone (rhGH)

Drug: Human Growth Hormone

Interventions

ACP-001 DRUG

Once weekly subcutaneous injection

ACP-001, dose-level 1; ACP-001, dose-level 2; ACP-001, dose-level 3

Human Growth Hormone DRUG

Once daily subcutaneous injection of human Growth Hormone

Also known as: Somatropin

Human Growth Hormone

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ascendis Pharma A/S: lead

Study Sites (36)

2nd Children City Clinic

Minsk, Belarus

Location

University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Marina"

Varna, Bulgaria

Location

Masaryk´s Hospital

Ústí nad Labem, Czechia

Location

El Shatby University Hospital

Alexandria, Egypt

Location

Ain Shams University Hospital

Cairo, Egypt

Location

Cairo University Hospital

Cairo, Egypt

Location

El Mansoura University Hospital

El Mansoura, Egypt

Location

Hôpital des enfants Pellegrin

Bordeaux, France

Location

Hôpital Jeanne de Flandre

Lille, France

Location

Hôpital Femme-Mère-Enfant

Lyon, France

Location

University Hospital Leipzig

Leipzig, Germany

Location

University Children's Hospital Magdeburg

Magdeburg, Germany

Location

Children's Hospital of Athens "P. A. Kyriakou"

Athens, Greece

Location

Buda Children's Hospital

Budapest, Hungary

Location

Heim Pal Children's Hospital

Budapest, Hungary

Location

University of Pecs

Pécs, Hungary

Location

University of Szeged

Szeged, Hungary

Location

University Medical Hospital

Katowice, Poland

Location

Medical University of Lublin

Lublin, Poland

Location

Regional Hospital N°2 Rzeszow

Rzeszów, Poland

Location

Children's Memorial Health Institute Warsaw

Warsaw, Poland

Location

Emergency Clinical Hospital Cluj-Napoca

Cluj-Napoca, Romania

Location

St. Spiridon County Clinic Emergency Hospital

Iași, Romania

Location

Louis Turcanu Emergency Hospital for Children Timisoara

Timișoara, Romania

Location

Federal State Budgetary Institution

Moscow, Russia

Location

St. Petersburg State Pediatric Medical Academy

Saint Petersburg, Russia

Location

Samara State Medical University

Samara, Russia

Location

Bashkir State Medical University

Ufa, Russia

Location

Children's University Hospital

Ljubljana, Slovenia

Location

Ankara University School of Medicine

Ankara, Turkey (Türkiye)

Location

Ege Üniversity

Izmir, Turkey (Türkiye)

Location

Donetsk Regional Children Clinical Hospital

Donetsk, Ukraine

Location

Kharkiv National Medical University

Kharkiv, Ukraine

Location

Institute of Endocrinology and Metabolism

Kiev, Ukraine

Location

Ukrainian Children Specialized Clinical Hospital

Kiev, Ukraine

Location

Odessa National Medical University

Odesa, Ukraine

Location

Related Publications (1)

• Chatelain P, Malievskiy O, Radziuk K, Senatorova G, Abdou MO, Vlachopapadopoulou E, Skorodok Y, Peterkova V, Leff JA, Beckert M; TransCon GH Working Group. A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency. J Clin Endocrinol Metab. 2017 May 1;102(5):1673-1682. doi: 10.1210/jc.2016-3776.

  PMID: 28201598 DERIVED

MeSH Terms

Conditions

Dwarfism, Pituitary

Interventions

Human Growth Hormone

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: VP Clinical Development
• Organization: Ascendis Pharma A/S

mb@ascendispharma.com

+49 172 155 2596

Study Officials

• Pierre Chatelain, Prof, MD

  University of Lyon

  PRINCIPAL INVESTIGATOR

• Michael Beckert, MD

  Ascendis Pharma A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2013
• First Posted: September 23, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: September 1, 2015
• Last Updated: January 19, 2017
• Results First Posted: January 19, 2017

Record last verified: 2016-11

Locations

SL (1); TU (2); DE (2); GR (1); FR (3); CZ (1); BE (1); HU (4); RO (3); UA (5); BU (1); PL (4); RU (4); EG (4)