Efficacy and Safety Evaluation of Recombinant Human Growth Hormone (r-hGH), Saizen®, on a Population of Children With Hypochondroplasia, Treated at Least 3 Years or Until Near Final Height, When Applicable, in Comparison With a Historic Cohort of Non-treated Children

NCT01111019 | Completed Phase 2 Results

• 1 other identifier: IMP 26545 (EMR701048-506)
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This study is conducted to describe the efficacy and safety of recombinant human growth hormone (r-hGH) treatment Saizen® on children with hypochondroplasia.

Conditions

Hypochondroplasia

Keywords

Hypochondroplasia; Skeletal dysplasia; Growth; Growth Hormone; Recombinant-human Growth Hormone

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects at Year 3

  Height was calculated in standardized units expressed as the standard deviation score (SDS), where SDS = (x - m)/sigma, in which x represents the height variable measured by sex and age, and m and sigma are the statistical parameters (mean and standard deviation) for the Sempe reference population. The reference population was the historical cohort consisting of non-treated subjects with Hypochondroplasia (HCH). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) a participant's value was relative to the mean of the reference population. The scores were centered around zero. Negative score indicated smaller height for the respective age/gender.

  Baseline (Month 0), Year 3

• Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects at Year 4

  Height was calculated in standardized units expressed as the standard deviation score (SDS), where SDS = (x - m)/sigma, in which x represents the height variable measured by sex and age, and m and sigma are the statistical parameters (mean and standard deviation) for the Sempe reference population. The reference population was the historical cohort consisting of non-treated subjects with Hypochondroplasia (HCH). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) a participant's value was relative to the mean of the reference population. The scores were centered around zero. Negative score indicated smaller height for the respective age/gender.

  Year 4

Secondary Outcomes (14)

• Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects

  Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)

• Change From Baseline in Height of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years

  Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)

• Change From Baseline in Upper Segment (Superior) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years

  Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)

• Change From Baseline in Weight of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years

  Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)

• Change From Baseline in Body Mass Index (BMI) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9.5 Years

  Baseline (Month 0), Year 1, 2, 3, 4, 5, 6, 7, 8 (both male and female); 8.5 (only for female), 9 (only for male) and 9.5 (only for male)

Study Arms (1)

r-hGH (Saizen®)

EXPERIMENTAL

Drug: Recombinant human growth hormone (r-hGH)

Interventions

Recombinant human growth hormone (r-hGH) DRUG

Subjects will receive a single subcutaneous injection of recombinant human growth hormone (r-hGH) equivalent to a dose of 0.057 milligram per kilogram per day (mg/kg/day). The dose will be subsequently adjusted during the trial and subjects will be treated for at least 3 years or until near final height is reached.

Also known as: Saizen®, Somatropin

r-hGH (Saizen®)

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female children with hypochondroplasia defined by a disproportional short limb height and a X-ray evidence of shortening of the long bones and failure of increase in the interpedicular distance between lumbar vertebrae L1 and L5
• Result of genetic analysis for mutation of gene FGFR3 already known or ongoing analysis at the beginning of the study
• Chronological age greater than or equal to 3 years
• Height for chronological age less than or equal to - 2 SDS
• Bone age less than or equal to 11 years for girls and 13 years for boys
• A written informed consent at the beginning of the pre-treatment period must be obtained from the parent(s)/legal guardian(s). Children able to understand the trial should personally sign and date the written informed consent
• Bone age at Month 36 or Month 60 is compatible with treatment prolongation according to investigator opinion
• Subject is still under r-hGH treatment with Saizen® at Month 36 or Month 60
• Height gain greater than or equal to + 1 SDS after the 2 first years of treatment for treatment prolongation at Month 36 and growth velocity greater than or equal to 5 centimeter (cm) per year, with bone age less than 14 years for females or less than 16 years for males for treatment prolongation at Month 60
• According to investigator opinion, gene mutations of the subjects are not in connection with observed side effects during the 3 or 5 first years of treatment
• An updated written informed consent must be obtained from the parent(s)/legal guardian(s) before the start of each study prolongation. Children able to understand the trial should personally sign and date the written informed consent

You may not qualify if:

• Turner's Syndrome in girls
• Active malignant neoplastic disease
• Severe congenital malformations
• Proliferative or preproliferative diabetic retinopathy
• Evidence of any progression or recurrence of an underlying intra-cranial space occupying lesion
• Severe psychomotor retardation
• Diabetes mellitus or history of significant glucose intolerance as defined by a fasting blood glucose greater than 6.4 millimole per liter (mmol/L)
• Known renal insufficiency as defined by serum creatinine level 1.0 milligram per deciliter (mg/dL) (88 micromole per liter \[mcmol/L\])
• Known hepatic disease as defined by elevated liver enzymes or total bilirubin (\* 2 Normal)
• Current congestive heart failure, untreated hypertension, serious chronic edema of any cause
• Chronic infectious disease
• History of intracranial hypertension with papilledema
• Previous or ongoing treatment with sex steroid therapy such as estrogens or testosterone
• Previous or ongoing treatment with any therapy that may directly influence growth, including Growth Hormone (GH), Growth Hormone Releasing Hormone (GHRH) and long duration corticosteroids therapy
• Known hypersensitivity to somatropin or any of the excipients

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Serono S.A.S, France: collaborator

Study Sites (1)

Endocrinologie Pédiatrique - centre des maladies rares de la croissance -Hôpital Necker Enfants Malades

Paris, 75015, France

Location

Related Publications (1)

• Pinto G, Cormier-Daire V, Le Merrer M, Samara-Boustani D, Baujat G, Fresneau L, Viaud M, Souberbielle JC, Pineau JC, Polak M. Efficacy and safety of growth hormone treatment in children with hypochondroplasia: comparison with an historical cohort. Horm Res Paediatr. 2014;82(6):355-63. doi: 10.1159/000364807. Epub 2014 Oct 15.

  PMID: 25323764 DERIVED

MeSH Terms

Conditions

Hypochondroplasia; Mucopolysaccharidosis IV

Interventions

Growth Hormone; Human Growth Hormone

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA

service@merckgroup.com

+49 6151 72 5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 23, 2010
• First Posted: April 27, 2010
• Study Start: March 21, 2006
• Primary Completion: January 17, 2017
• Study Completion: January 17, 2017
• Last Updated: February 15, 2019
• Results First Posted: February 15, 2019

Record last verified: 2018-10

Locations

FR (1)