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HypochondroplasiaPhase 2NCT01111019

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

A Phase 2 study testing Recombinant human growth hormone (r-hGH) in people with Hypochondroplasia, run by Merck KGaA, Darmstadt, Germany at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 3 years and older
Conditions the study is for
Hypochondroplasia
What is being tested?
Recombinant human growth hormone (r-hGH)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteFrance
Study dates
21 Mar 2006to 17 Jan 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • Additional inclusion criteria for each study prolongation:
  • 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

Who cannot join

  • 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
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  • 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
  • Epiphyseal fusion
  • Participation to any clinical study within the 30 days preceding study entry
  • Pregnant females

Trial locations and contacts

1 site in 1 country.

France1 site

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

    Paris, 75015

Other trials in France

About this study

Official title: Efficacy and Safety Evaluation of Recombinant Human Growth Hormone (r-hGH), Saizen®, on a Population of Children With Hypochondroplasia, Treated Over a Period of 3 Years or 5 Years if Applicable, in Comparison With a Historic Cohort of Non-treated Children With Hypochondroplasia

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

Being tested
Recombinant human growth hormone (r-hGH)
Keywords
Hypochondroplasia, Skeletal dysplasia, Growth, Growth Hormone, Recombinant-human Growth Hormone
Medical subject headings
Hypochondroplasia, Mucopolysaccharidosis IV

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Recombinant human growth hormone (r-hGH)Drug

    Also called Saizen®, Somatropin

    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.

Study groups in NCT01111019
Study groupRoleWhat they receive
r-hGH (Saizen®)ExperimentalNot described
Receives: Drug: Recombinant human growth hormone (r-hGH)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline (Month 0), Year 3

  2. 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.

    Measured: Year 4

Secondary outcomes (14)

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

    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). Data was reported by gender. Male subjects were analyzed till 9.5 years and female subjects were analyzed till 8.5 years. 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.

    Measured: 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)

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

    Body proportion was measured in terms of height. Data was reported by gender. Male subjects were analyzed till 9.5 years and female subjects were analyzed till 8.5 years.

    Measured: 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)

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

    Body proportion was measured in terms of upper segment for standing and sitting position. Data was reported by gender. Male subjects were analyzed till 9.5 years and female subjects were analyzed till 8.5 years.

    Measured: 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)

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

    The body weight was measured on a certified and calibrated hospital scale. Data was reported by gender. Male subjects were analyzed till 9.5 years and female subjects were analyzed till 8.5 years.

    Measured: 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)

  5. 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

    Body proportion measured as BMI. It was calculated according to the formula BMI = Weight (kilogram)/Height square (meter square). Data was reported by gender. Male subjects were analyzed till 9.5 years and female subjects were analyzed till 8.5 years.

    Measured: 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)

  6. Change From Baseline in Bone Mineral Density (BMD) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9 Years

    Body composition measured as BMD. It was examined at the lumbar spine (L1-L4) and determined annually by dual-energy X-ray absorptiometry. Data was reported by gender. Male subjects were analyzed till 9 years and female subjects were analyzed till 8 years.

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

  7. Change From Baseline in Percent Body Fat Mass of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9 Years

    Body composition measured as percentage of body fat mass. It was measured by Dual X-ray absorptiometry. Data was reported by gender. Male subjects were analyzed till 9 years and female subjects were analyzed till 8 years.

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

  8. Change From Baseline in Lean Body Mass (LBM) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) up to 9 Years

    Body composition measured as LBM. It was measured by Dual X-ray absorptiometry. Data was reported by gender. Male subjects were analyzed till 9 years and female subjects were analyzed till 8 years.

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

  9. Growth (Height) Velocity of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years

    Growth velocity was calculated in terms of height velocity. It corresponded to a difference in height between current and baseline values divided by the time interval between both evaluations. Data was reported by gender. Male subjects were analyzed till 9.5 years and female subjects were analyzed till 8.5 years.

    Measured: 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)

  10. Head Circumference Values of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years

    Body proportion was measured in terms of head circumference with a tape measure. Data was reported by gender. Male subjects were analyzed till 9.5 years and female subjects were analyzed till 8.5 years.

    Measured: 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)

  11. Osteocalcin Values of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years

    Osteocalcin as bone marker was analyzed with the Immunology system Elecsys. Data was reported by gender. Male subjects were analyzed till 9.5 years and female subjects were analyzed till 8.5 years.

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

  12. C-terminal Telopeptide (CTX) Values of Recombinant Human Growth Hormone (r-hGH) Treated Subjects With Hypochondroplasia (HCH) From Year 1 up to 9.5 Years

    CTX (Blood) as bone marker was analyzed with the Immunology system Elecsys. Data was reported by gender. Male subjects were analyzed till 9.5 years and female subjects were analyzed till 8.5 years.

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

  13. Number of Subjects With Fibroblast Growth Factor Receptor (FGFR3) Mutation

    Genetic analysis was performed to record FGFR3 gene mutation. Genomic DNA was extracted from lymphocytes of collected blood samples using standard procedures. A set of intronic primers was designed based on the genomic sequence of the human FGFR3 gene and used to amplify exons 2-19. Number of subjects with FGFR3 mutation were reported.

    Measured: Baseline up to 3 years

  14. Number of Subjects With Adverse Event (AE) and Serious Adverse Event (SAE)

    AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug , SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose.

    Measured: Baseline up to 9.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2010 (estimated)
  2. Study start21 Mar 2006
  3. Primary completion17 Jan 2017
  4. Study completion17 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01111019
Sponsor's protocol ID
IMP 26545 (EMR701048-506)
Status last verified
Oct 2018
First submitted
23 Apr 2010
Last updated
15 Feb 2019
Data monitoring committee
No

Publications

  • 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.

    PubMed 25323764

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Recombinant human growth hormone (r-hGH) in people with Hypochondroplasia, run by Merck KGaA, Darmstadt, Germany at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Height-Standard Deviation Score (H-SDS) of Recombinant Human Growth Hormone (r-hGH) Treated Subjects at Year 3 (time frame: Baseline (Month 0), Year 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01111019, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2019.

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