Foetal Growth ProblemPhase 3NCT00184717

Growth Hormone Treatment in Children Born Small for Gestational Age (SGA)

A Phase 3 study testing somatropin in people with Foetal Growth Problem and Small for Gestational Age, run by Novo Nordisk A/S at 1 site in Japan.

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 in Japan. The aim of this trial is to assess the efficacy and safety of somatropin in children born small for gestational age (SGA) in Japan. In the main period, subjects will receive either active treatment for 104 weeks (two dosing regimens) or no treatment for 52 weeks followed by an… Read more about this study

Who is it for?: Ages 3 to 8 years
Conditions the study is for: Foetal Growth Problem, Small for Gestational Age
What is being tested?: somatropin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 98 participants
Where: 1 siteJapan
Study dates: 18 Aug 2004to 28 Dec 2009
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 3 to 8 years
All sexes
No healthy volunteers
Child

Who may be able to join

For MAIN period (GHLIQUID-1516):
Born small for gestational age (SGA) with birth weight and birth length below the 10th percentile for gestational age, and additional either birth length below or equal to -2.0 standard deviation score (SDS) or birth weight below or equal to -2.0 SDS for gestational age
Growth failure with height at -2.0 SDS or below for chronological age (CA)
Normal growth hormone (GH) production, defined as peak GH level > 10 ng/mL in one GH provocation test
For EXTENSION period (GHLIQUID-1517):
Subjects who completed the main period
Chronological age (CA) for boys at least 4 years, but maximum 11 years
Chronological age (CA) for girls at least 4 years, but maximum 10 years

Who cannot join

Subjects with diabetes mellitus
Subjects suffering from malignancy
Several medical conditions

Trial locations and contacts

1 site in 1 country.

Japan1 site

Novo Nordisk Investigational Site
Tokyo, 1000005

Other trials in Japan

About this study

Official title: GHLIQUID-1516: A 104-week, Multi-centre, Randomised, Double-blind, Parallel-group, no Treatment Controlled (Open-label) Trial Investigating the Efficacy and Safety of Two Doses of NN-220 in Subjects With Short Stature Born Small for Gestational Age / GHLIQUID-1517: A Long-term, Multi-centre, Randomised, Controlled, Double-blind, Parallel-group Trial, Investigating the Efficacy and Safety of Two Doses of NN-220 in Subjects With Short Stature Born Small for Gestational Age

This study is conducted in Japan. The aim of this trial is to assess the efficacy and safety of somatropin in children born small for gestational age (SGA) in Japan.

In the main period, subjects will receive either active treatment for 104 weeks (two dosing regimens) or no treatment for 52 weeks followed by an extension period where subjects who received active treatment for 104 weeks (two years) will continue with the same treatment for further 156 weeks (three years) while those subjects who received no treatment for 52 weeks (one year) will be randomised to receive two dosing regimens for 208 weeks (four years). In total, subjects participate in trial for 260 weeks (five years).

Main period is registered internally at Novo Nordisk as GHLIQUID-1516 while the extension period is registered as GHLIQUID-1517.

Conditions: Foetal Growth Problem, Small for Gestational Age
Being tested: somatropin

What participants receive

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

somatropinDrug
0.033 mg/kg/day of NN-220 for s.c. injection in cartridge
somatropinDrug
0.067 mg/kg/day of NN-220 for s.c. injection in cartridge

Study groups in NCT00184717
Study group	Role	What they receive
0.033 mg / NN-220	Experimental	In the 156-week main period, subjects received 0.033 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime followed by a 104-week extension period where subjects received 0.033 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime Receives: Drug: somatropin
0.067 mg / NN-220	Experimental	In the 156-week main period, subjects received 0.067 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime followed by a 104-week extension period where subjects received 0.067 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime Receives: Drug: somatropin
No treatment	No intervention	No somatropin (NN-220) treatment was given in the 52-week main period. Subjects was re-randomised to recive two dosing regimens (0.033 mg/kg/day or 0.067 mg/kg/day) in the 208-week extension period
No treatment --> 0.033 mg	Experimental	In the 208-week extension period, subjects received 0.033 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime after having received no somatromin (NN-220) treatment in the 52-week main period Receives: Drug: somatropin
No treatment --> 0.067 mg	Experimental	In the 208-week extension period, subjects received 0.067 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime after having received no somatromin (NN-220) treatment in the 52-week main period Receives: Drug: somatropin

What is being measured

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

Change in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Week 260 - Subjects Received NN220 Treatment for 5 Years
Height SDS for chronological age were derived as follow; {Height - mean (age, sex)}/ SD (age, sex), where mean (age, sex) and SD (age, sex) were mean and SD of height for corresponding chronological age and sex (data of those in 2000). Height SDS was calculated using mean of three height observations at corresponding visit
Measured: Week 0, week 260
Change in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Week 208 - Subjects Received NN220 Treatment for 4 Years
Height SDS for chronological age were derived as follow; {Height - mean (age, sex)}/ SD (age, sex), where mean (age, sex) and SD (age, sex) were mean and SD of height for corresponding chronological age and sex (data of those in 2000). Height SDS was calculated using mean of three height observations at corresponding visit
Measured: Week 0, week 208

Secondary outcomes (6)

Yearly Height Velocity SDS for Chronological Age - Subjects Received NN220 Treatment for 5 Years
Yearly Height velocity SDS for chronological age were summarised and graphically presented
Measured: Weeks 0-260
Yearly Height Velocity SDS for Chronological Age - Subjects Received NN220 Treatment for 4 Years
Yearly Height velocity SDS for chronological age were summarised and graphically presented
Measured: Weeks 0-208
Change in Bone Age (Left Hand X-Ray) at Week 260 - Subjects Received NN220 Treatment for 5 Years
Bone age is measured as years and months (displayed as xx.x years). Change in Bone age = Bone age at 52*i weeks - Bone age at 52*(i-1) weeks, i=1, 2, ….
Measured: Week 0, week 260
Change in Bone Age (Left Hand X-Ray) at Week 208 - Subjects Received NN220 Treatment for 4 Years
Bone age is measured as years and months (displayed as xx.x years).Change in Bone age = Bone age at 52*i weeks - Bone age at 52*(i-1) weeks, i=1, 2, ….
Measured: Week 0, week 208
Adverse Events - Subjects Received NN220 Treatment for 5 Years
Occurrence of Adverse Events (AEs) during treatment period (TEAEs), occurrence of possibly/probably related AEs during the treatment period, and occurrence of Serious Adverse Events (SAEs) during the treatment period. An AE is any undesirable medical event occurring to a subject in a clinical trial, whether or not related to the trial product(s). An SAE is an experience that at any dose is fatal, life-threatening, disabling or which results in the patient being hospitalised or, if already in hospital, that hospitalisation is prolonged, or ocurrence of congenital anomaly
Measured: Weeks 0-260
Adverse Events - Subjects Received NN220 Treatment for 4 Years
Occurrence of Adverse Events (AEs) during treatment period (TEAEs), occurrence of possibly/probably related AEs during the treatment period, and occurrence of Serious Adverse Events (SAEs) during the treatment period. An AE is any undesirable medical event occurring to a subject in a clinical trial, whether or not related to the trial product(s). An SAE is an experience that at any dose is fatal, life-threatening, disabling or which results in the patient being hospitalised or, if already in hospital, that hospitalisation is prolonged, or ocurrence of congenital anomaly
Measured: Weeks 0-208

Timeline

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

18 Aug 200428 Dec 2009

First posted16 Sep 2005 (estimated)
Study start18 Aug 2004
Primary completion29 Mar 2006
Study completion28 Dec 2009

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 Foetal Growth ProblemStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
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: Double blind
Who is masked: Participant, Investigator
Enrolment: 98 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00184717
Sponsor's protocol ID: GHLIQUID-1517
Other IDs: JapicCTI-050137, JapicCTI-050132, 2017-000914-47, 2017
Status last verified: Jun 2017
First submitted: 13 Sep 2005
Last updated: 7 Jul 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Tanaka T, Yokoya S, Seino Y, Togari H, Mishina J, Kappelgaard AM, Fujieda K. Long-term efficacy and safety of two doses of growth hormone in short Japanese children born small for gestational age. Horm Res Paediatr. 2011;76(6):411-8. doi: 10.1159/000334152. Epub 2011 Nov 29.
PubMed 22156542
Kappelgaard AM, Kiyomi F, Horikawa R, Yokoya S, Tanaka T. The impact of long-term growth hormone treatment on metabolic parameters in Japanese patients with short stature born small for gestational age. Horm Res Paediatr. 2014;81(4):272-9. doi: 10.1159/000358196. Epub 2014 Feb 11.
PubMed 24526136
Horikawa R, Tanaka T, Nishinaga H, Ogawa Y, Yokoya S. The influence of a long-term growth hormone treatment on lipid and glucose metabolism: a randomized trial in short Japanese children born small for gestational age. Int J Pediatr Endocrinol. 2016;2016:19. doi: 10.1186/s13633-016-0036-4. Epub 2016 Oct 26.
PubMed 27799945

Study at a glance

From the registry record, last updated by the sponsor on 7 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: GHLIQUID-1516: A 104-week, Multi-centre, Randomised, Double-blind, Parallel-group, no Treatment Controlled (Open-label) Trial Investigating the Efficacy and Safety of Two Doses of NN-220 in Subjects With Short Stature Born Small for Gestational Age / GHLIQUID-1517: A Long-term, Multi-centre, Randomised, Controlled, Double-blind, Parallel-group Trial, Investigating the Efficacy and Safety of Two Doses of NN-220 in Subjects With Short Stature Born Small for Gestational Age
ClinicalTrials.gov ID: NCT00184717
Acronym / sponsor ID: GHLIQUID-1517
Conditions: Foetal Growth Problem, Small for Gestational Age
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 98 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: 18 Aug 2004 (actual)
Primary completion: 29 Mar 2006 (actual)
Study completion: 28 Dec 2009 (actual)
First posted: 16 Sep 2005 (estimated)
Results: Posted 7 Jul 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is conducted in Japan. The aim of this trial is to assess the efficacy and safety of somatropin in children born small for gestational age (SGA) in Japan.

Main period is registered internally at Novo Nordisk as GHLIQUID-1516 while the extension period is registered as GHLIQUID-1517.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
0.033 mg / NN-220	Experimental	Drug: somatropinIn the 156-week main period, subjects received 0.033 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime followed by a 104-week extension period where subjects received 0.033 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime
0.067 mg / NN-220	Experimental	Drug: somatropinIn the 156-week main period, subjects received 0.067 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime followed by a 104-week extension period where subjects received 0.067 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime
No treatment	No intervention	–No somatropin (NN-220) treatment was given in the 52-week main period. Subjects was re-randomised to recive two dosing regimens (0.033 mg/kg/day or 0.067 mg/kg/day) in the 208-week extension period
No treatment --> 0.033 mg	Experimental	Drug: somatropinIn the 208-week extension period, subjects received 0.033 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime after having received no somatromin (NN-220) treatment in the 52-week main period
No treatment --> 0.067 mg	Experimental	Drug: somatropinIn the 208-week extension period, subjects received 0.067 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime after having received no somatromin (NN-220) treatment in the 52-week main period

Who may qualify

Ages: 3 to 8 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (8 listed)

For MAIN period (GHLIQUID-1516):
Born small for gestational age (SGA) with birth weight and birth length below the 10th percentile for gestational age, and additional either birth length below or equal to -2.0 standard deviation score (SDS) or birth weight below or equal to -2.0 SDS for gestational age
Growth failure with height at -2.0 SDS or below for chronological age (CA)
Normal growth hormone (GH) production, defined as peak GH level > 10 ng/mL in one GH provocation test
For EXTENSION period (GHLIQUID-1517):

Key exclusion criteria (3 listed)

Subjects with diabetes mellitus
Subjects suffering from malignancy
Several medical conditions

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
somatropin0.033 mg/kg/day of NN-220 for s.c. injection in cartridge	Drug	0.033 mg / NN-220, No treatment --> 0.033 mg
somatropin0.067 mg/kg/day of NN-220 for s.c. injection in cartridge	Drug	0.067 mg / NN-220, No treatment --> 0.067 mg

Primary outcome

Change in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Week 260 - Subjects Received NN220 Treatment for 5 Years
Time frame: Week 0, week 260
Height SDS for chronological age were derived as follow; {Height - mean (age, sex)}/ SD (age, sex), where mean (age, sex) and SD (age, sex) were mean and SD of height for corresponding chronological age and sex (data of those in 2000). Height SDS was calculated using mean of three height observations at corresponding visit
Change in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Week 208 - Subjects Received NN220 Treatment for 4 Years
Time frame: Week 0, week 208
Height SDS for chronological age were derived as follow; {Height - mean (age, sex)}/ SD (age, sex), where mean (age, sex) and SD (age, sex) were mean and SD of height for corresponding chronological age and sex (data of those in 2000). Height SDS was calculated using mean of three height observations at corresponding visit

6 secondary outcomes

Yearly Height Velocity SDS for Chronological Age - Subjects Received NN220 Treatment for 5 Years
Time frame: Weeks 0-260
Yearly Height Velocity SDS for Chronological Age - Subjects Received NN220 Treatment for 4 Years
Time frame: Weeks 0-208
Change in Bone Age (Left Hand X-Ray) at Week 260 - Subjects Received NN220 Treatment for 5 Years
Time frame: Week 0, week 260
Change in Bone Age (Left Hand X-Ray) at Week 208 - Subjects Received NN220 Treatment for 4 Years
Time frame: Week 0, week 208
Adverse Events - Subjects Received NN220 Treatment for 5 Years
Time frame: Weeks 0-260
Adverse Events - Subjects Received NN220 Treatment for 4 Years
Time frame: Weeks 0-208

Results and safety

Results posted to the registry on 7 Jul 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
0.033 mg / NN-220	39	36
0.067 mg / NN-220	38	36
No Treatment	21	20
No Treatment --> 0.033 mg	0	0
No Treatment --> 0.067 mg	0	0

Primary outcome: Change in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Week 260 - Subjects Received NN220 Treatment for 5 Years

Time frame: Week 0, week 260. Least squares mean (Standard Error). Unit: Standard Deviation Score (SDS)

Measure	0.033 mg / NN-220 n = 28	0.067 mg / NN-220 n = 29	No Treatment --> 0.033 mg n = 0	No Treatment --> 0.067 mg n = 0
Week 0	-2.9488 (0.6368)	-2.9047 (0.6718)	–	–
Week 260	1.2066 (0.1102)	2.0247 (0.1083)	–	–

Population analysed: Endpoint Analysis Set (EAS) consisted of subjects who participated in GHLIQUID-1517 in the Full Analysis Set (FAS). FAS consisted of subjects who were randomised in each group and have any available efficacy data after receiving NN-220 in GHLIQUID-1516 or GHLIQUID-1517, except subjects with GCP (Good Clinical Practice) nonconformity

Primary outcome: Change in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Week 208 - Subjects Received NN220 Treatment for 4 Years

Time frame: Week 0, week 208. Least squares mean (Standard Error). Unit: Standard Deviation Score (SDS)

Measure	0.033 mg / NN-220 n = 0	0.067 mg / NN-220 n = 0	No Treatment --> 0.033 mg n = 7	No Treatment --> 0.067 mg n = 8
Week 0	–	–	-2.9603 (0.6689)	-2.7481 (0.3524)
Week 208	–	–	1.0997 (0.2453)	1.9151 (0.2275)

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: The adverse events were collected from Aug 2004 to Dec 2009.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
0.033 mg / NN-220	12 of 31 (38.7%)	31 of 31 (100%)	Not reported
0.067 mg / NN-220	11 of 34 (32.4%)	34 of 34 (100%)	Not reported
0.033 mg / No Treatment	1 of 7 (14.3%)	7 of 7 (100%)	Not reported
0.067 mg / No Treatment	2 of 8 (25%)	8 of 8 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 22156542Tanaka T, Yokoya S, Seino Y, Togari H, Mishina J, Kappelgaard AM, Fujieda K. Long-term efficacy and safety of two doses of growth hormone in short Japanese children born small for gestational age. Horm Res Paediatr. 2011;76(6):411-8. doi: 10.1159/000334152. Epub 2011 Nov 29.
Results publication: PubMed 24526136Kappelgaard AM, Kiyomi F, Horikawa R, Yokoya S, Tanaka T. The impact of long-term growth hormone treatment on metabolic parameters in Japanese patients with short stature born small for gestational age. Horm Res Paediatr. 2014;81(4):272-9. doi: 10.1159/000358196. Epub 2014 Feb 11.
Derived from this study: PubMed 27799945Horikawa R, Tanaka T, Nishinaga H, Ogawa Y, Yokoya S. The influence of a long-term growth hormone treatment on lipid and glucose metabolism: a randomized trial in short Japanese children born small for gestational age. Int J Pediatr Endocrinol. 2016;2016:19. doi: 10.1186/s13633-016-0036-4. Epub 2016 Oct 26.
Clinical Trials at Novo NordiskLink provided by the sponsor.

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.

Global Clinical Registry (GCR, 1452) study director

Novo Nordisk A/S

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing somatropin in people with Foetal Growth Problem and Small for Gestational Age, run by Novo Nordisk A/S at 1 site in Japan.

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 8 inclusion and 3 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 7 Jul 2017. 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 Japan. 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 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 7 Jul 2011). 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 in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Week 260 - Subjects Received NN220 Treatment for 5 Years (time frame: Week 0, week 260). 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 NCT00184717, 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 7 Jul 2017.