Children Born With Serious Intra-uterine Growth RetardationPhase 3NCT01400698
Saizen in Intra-uterine Growth Retardation
A Phase 3 study testing Saizen® A, Saizen® B and Observation only in people with Children Born With Serious Intra-uterine Growth Retardation, run by Merck KGaA, Darmstadt, Germany.
Trial summary
Study of safety of Saizen® in children born with serious intra-uterine growth retardation (IUGR) treated to final height. An open, phase III study involving 17 centers in France. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Children Born With Serious Intra-uterine Growth Retardation
- What is being tested?
- Saizen® A, Saizen® B and Observation only
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- No sites listed yet
- Study dates
- Nov 1998to Feb 2010
- Phase
- Phase 3
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Previous inclusion, good compliance and normal completion of GF4001 or GF6283 in the treatment of growth failure in children born with serious IUGR (3-year continuous r-hGH treatment in GF4001 or 2-year continuous or intermittent r-hGH treatment in GF6283).
- Increase in height greater than 0.5 standard deviation (SD) during the first 2 years of r-hGH treatment in GF4001 or after 2 years of continuous or intermittent r-hGH treatment in GF6283.
- A written Informed Consent at the beginning of the pre-study visit must be obtained from the parent(s)/legal guardian(s), with the understanding that consent may be withdrawn by the subject or parents at any time without prejudice to their future medical care. Children able to understand the trial should personally sign and date the written informed consent, too.
- Other protocol-defined inclusion criteria may apply.
Who cannot join
- Known multiple malformation syndrome with severe psychomotor retardation and/or body hemihypertrophy.
- Severe psychomotor retardation.
- Severe congenital malformations.
- Other protocol-defined exclusion criteria may apply.
About this study
Official title: An Open Study of the Safety and Efficacy of Saizen®, (Recombinant Human Growth Hormone, r-hGH), in Children Born With Serious Intra-uterine Growth Retardation (IUGR) Treated to Final Height
Study of safety of Saizen® in children born with serious intra-uterine growth retardation (IUGR) treated to final height. An open, phase III study involving 17 centers in France.
The study enrolled children who have completed 3 or 2 years of treatment and at least one year of post treatment observation in the Sponsor Studies GF 4001 (Safety and Efficacy of Saizen in the Treatment of Young Children Born with Severe IUGR) or GF 6283 (Effect of Intermittent versus Continuous Saizen Therapy in Young Children Born with Severe IUGR), respectively.
Read more
Detailed description: Serious IUGR is a syndrome characterized by low birth length and weight for gestational age (less than 10 percentile). The secretion of growth hormone in response to provocative stimuli (e.g. arginine, insulin) is normal in these children. Apart from low birth weight, children born with IUGR may have minor or major malformations.
A catch-up period with a supraphysiological growth velocity generally occurs during the first 6 to 24 months of life in 80 to 90 percent (%) of these children. This generally allows them to reach normal height. That means that conversely, approximately 10 to 20% of children do maintain a statural handicap. Puberty occurs at a normal age and the retardation in bone maturation present during the first years of life disappears very quickly. This leads to short adult stature in subjects who have not shown spontaneous catch-up during the first years of life. A safe and effective means of promoting growth without accelerating the timing or tempo of puberty would therefore be desirable.
- Being tested
- Saizen® A, Saizen® B, Observation only
- Keywords
- Intra-uterine growth retardation (IUGR), Saizen, Recombinant human growth hormone (r-hGH), Final height, Bone age, SGA (Small for Gestational Age)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saizen® ADrug
Also called r-hGH, Somatropin
Continuous or intermittent treatment with recombinant human Growth Hormone (r-hGH) 0.067 milligram/kilogram/day (mg/kg/day) subcutaneously (sc).
Saizen® BDrug
Also called r-hGH, Somatropin
Observed until the first signs of puberty and then continuous treatment with r-hGH 0.067 mg/kg/day sc or observed without treatment.
Observation onlyOther
Subjects were only observed.
| Study group | Role | What they receive |
|---|---|---|
| Saizen® (Continuous or intermittent treatment) | Experimental | Not described Receives: Drug: Saizen® A |
| Saizen® (Observed and then continuous or no treatment) | Experimental | Not described Receives: Drug: Saizen® B |
| Observation only | Other | Not described Receives: Other: Observation only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Final Height
Final height was defined as the height reached 1 year after height velocity (HV) was less than 2 centimeter/year (cm/year). Height velocity was the change in height since the previous year's measurement. Height was measured with a wall-mounted stadiometer (or in supine position if the participant's age was less than 3 years) and the measurement was repeated thrice by the same observer. The mean of the values obtained in the repeated measurements was taken for the analysis.
Measured: One year after final height was attained up to 10.6 years
Height Standard Deviation Score (HSDS)
HSDS was calculated as height minus reference mean height divided by SD of the reference mean height, both given by the reference growth table (Sempe) for the corresponding chronological age at the height measurement. Greater HSDS indicate greater height. (Sempe M et al., 1979)
Measured: One year after final height was attained up to 10.6 years
Secondary outcomes (1)
Parental Adjusted Height Standard Deviation Score (PAHSDS)
PAHSDS is the distance between the participant's current and target heights, expressed in units of SD of the height distribution of the reference population. Target height is a measure of the height which the participant could hypothetically reach based only on his parents' heights. Target height standard deviation score (THSDS) was calculated as target height minus mean adult height of the reference population divided by SD of the mean adult height of the reference population.
Measured: One year after final height was attained up to 10.6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2011 (estimated)
- Study startNov 1998
- Primary completionFeb 2010
- Study completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Children Born With Serious Intra-uterine Growth RetardationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Serono S.A., Geneva
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Serono S.A., Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01400698
- Sponsor's protocol ID
- 20184
- Status last verified
- Sep 2013
- First submitted
- 21 Jul 2011
- Last updated
- 18 Sep 2013
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Sempé M, Pédron G, Roy-Pernot M-P. Auxologie, méthode et séquences. Paris: Theraplix, 1979.
Simon D, Leger J, Fjellestad-Paulsen A, Crabbe R, Czernichow P; SGA Study Group. Intermittent recombinant growth hormone treatment in short children born small for gestational age: four-year results of a randomized trial of two different treatment regimens. Horm Res. 2006;66(3):118-23. doi: 10.1159/000093832. Epub 2006 Jun 12.
PubMed 16772718Fjellestad-Paulsen A, Czernichow P, Brauner R, Bost M, Colle M, Lebouc JY, Lecornu M, Leheup B, Limal JM, Raux MC, Toublanc JE, Rappaport R. Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation. Acta Paediatr. 1998 May;87(5):511-7. doi: 10.1080/08035259850158209.
PubMed 9641731
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Study of the Safety and Efficacy of Saizen®, (Recombinant Human Growth Hormone, r-hGH), in Children Born With Serious Intra-uterine Growth Retardation (IUGR) Treated to Final Height
- ClinicalTrials.gov ID
- NCT01400698
- Acronym / sponsor ID
- 20184
- Keywords
- Intra-uterine growth retardation (IUGR), Saizen, Recombinant human growth hormone (r-hGH), Final height, Bone age, SGA (Small for Gestational Age)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Serono S.A., Geneva
- Study start
- Nov 1998
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 22 Jul 2011 (estimated)
- Results
- Posted 25 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study of safety of Saizen® in children born with serious intra-uterine growth retardation (IUGR) treated to final height. An open, phase III study involving 17 centers in France.
The study enrolled children who have completed 3 or 2 years of treatment and at least one year of post treatment observation in the Sponsor Studies GF 4001 (Safety and Efficacy of Saizen in the Treatment of Young Children Born with Severe IUGR) or GF 6283 (Effect of Intermittent versus Continuous Saizen Therapy in Young Children Born with Severe IUGR), respectively.
Detailed description: Serious IUGR is a syndrome characterized by low birth length and weight for gestational age (less than 10 percentile). The secretion of growth hormone in response to provocative stimuli (e.g. arginine, insulin) is normal in these children. Apart from low birth weight, children born with IUGR may have minor or major malformations.
A catch-up period with a supraphysiological growth velocity generally occurs during the first 6 to 24 months of life in 80 to 90 percent (%) of these children. This generally allows them to reach normal height. That means that conversely, approximately 10 to 20% of children do maintain a statural handicap. Puberty occurs at a normal age and the retardation in bone maturation present during the first years of life disappears very quickly. This leads to short adult stature in subjects who have not shown spontaneous catch-up during the first years of life. A safe and effective means of promoting growth without accelerating the timing or tempo of puberty would therefore be desirable.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Saizen® (Continuous or intermittent treatment) | Experimental | Drug: Saizen® A |
| Saizen® (Observed and then continuous or no treatment) | Experimental | Drug: Saizen® B |
| Observation only | Other | Other: Observation only |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Previous inclusion, good compliance and normal completion of GF4001 or GF6283 in the treatment of growth failure in children born with serious IUGR (3-year continuous r-hGH treatment in GF4001 or 2-year continuous or intermittent r-hGH treatment in GF6283).
- Increase in height greater than 0.5 standard deviation (SD) during the first 2 years of r-hGH treatment in GF4001 or after 2 years of continuous or intermittent r-hGH treatment in GF6283.
- A written Informed Consent at the beginning of the pre-study visit must be obtained from the parent(s)/legal guardian(s), with the understanding that consent may be withdrawn by the subject or parents at any time without prejudice to their future medical care. Children able to understand the trial should personally sign and date the written informed consent, too.
- Other protocol-defined inclusion criteria may apply.
Key exclusion criteria (4 listed)
- Known multiple malformation syndrome with severe psychomotor retardation and/or body hemihypertrophy.
- Severe psychomotor retardation.
- Severe congenital malformations.
- Other protocol-defined exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Saizen® AAlso: r-hGH, SomatropinContinuous or intermittent treatment with recombinant human Growth Hormone (r-hGH) 0.067 milligram/kilogram/day (mg/kg/day) subcutaneously (sc). | Drug | Saizen® (Continuous or intermittent treatment) |
| Saizen® BAlso: r-hGH, SomatropinObserved until the first signs of puberty and then continuous treatment with r-hGH 0.067 mg/kg/day sc or observed without treatment. | Drug | Saizen® (Observed and then continuous or no treatment) |
| Observation onlySubjects were only observed. | Other | Observation only |
Primary outcome
Final Height
Time frame: One year after final height was attained up to 10.6 years
Final height was defined as the height reached 1 year after height velocity (HV) was less than 2 centimeter/year (cm/year). Height velocity was the change in height since the previous year's measurement. Height was measured with a wall-mounted stadiometer (or in supine position if the participant's age was less than 3 years) and the measurement was repeated thrice by the same observer. The mean of the values obtained in the repeated measurements was taken for the analysis.
Height Standard Deviation Score (HSDS)
Time frame: One year after final height was attained up to 10.6 years
HSDS was calculated as height minus reference mean height divided by SD of the reference mean height, both given by the reference growth table (Sempe) for the corresponding chronological age at the height measurement. Greater HSDS indicate greater height. (Sempe M et al., 1979)
1 secondary outcome
Parental Adjusted Height Standard Deviation Score (PAHSDS)
Time frame: One year after final height was attained up to 10.6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundSempé M, Pédron G, Roy-Pernot M-P. Auxologie, méthode et séquences. Paris: Theraplix, 1979.
- Results publication: PubMed 16772718Simon D, Leger J, Fjellestad-Paulsen A, Crabbe R, Czernichow P; SGA Study Group. Intermittent recombinant growth hormone treatment in short children born small for gestational age: four-year results of a randomized trial of two different treatment regimens. Horm Res. 2006;66(3):118-23. doi: 10.1159/000093832. Epub 2006 Jun 12.
- Results publication: PubMed 9641731Fjellestad-Paulsen A, Czernichow P, Brauner R, Bost M, Colle M, Lebouc JY, Lecornu M, Leheup B, Limal JM, Raux MC, Toublanc JE, Rappaport R. Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation. Acta Paediatr. 1998 May;87(5):511-7. doi: 10.1080/08035259850158209.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Serono S.A., Geneva
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Saizen® A, Saizen® B and Observation only in people with Children Born With Serious Intra-uterine Growth Retardation, run by Merck KGaA, Darmstadt, Germany.
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 4 inclusion and 4 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 18 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 25 Sep 2012). 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?
Final Height (time frame: One year after final height was attained up to 10.6 years). 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 NCT01400698, which also lists 3 linked publications.
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 18 Sep 2013.