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

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.

Study Overview

• Status: Completed
• Conditions: Foetal Growth Problem; Small for Gestational Age
• Intervention / Treatment: Drug: somatropin; Drug: somatropin

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 1000005
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 8 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• Subjects with diabetes mellitus
• Subjects suffering from malignancy
• Several medical conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.033 mg / NN-220; 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	Drug: somatropin; 0.033 mg/kg/day of NN-220 for s.c. injection in cartridge; Drug: somatropin; 0.067 mg/kg/day of NN-220 for s.c. injection in cartridge
Experimental: 0.067 mg / NN-220; 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	Drug: somatropin; 0.033 mg/kg/day of NN-220 for s.c. injection in cartridge; Drug: somatropin; 0.067 mg/kg/day of NN-220 for s.c. injection in cartridge
No Intervention: No treatment; 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
Experimental: No treatment --> 0.033 mg; 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	Drug: somatropin; 0.033 mg/kg/day of NN-220 for s.c. injection in cartridge; Drug: somatropin; 0.067 mg/kg/day of NN-220 for s.c. injection in cartridge
Experimental: No treatment --> 0.067 mg; 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	Drug: somatropin; 0.033 mg/kg/day of NN-220 for s.c. injection in cartridge; Drug: somatropin; 0.067 mg/kg/day of NN-220 for s.c. injection in cartridge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Week 0, week 208

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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, ….	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, ….	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	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	Weeks 0-208

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General 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.
• 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.
• 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.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2004
• Primary Completion (Actual): March 29, 2006
• Study Completion (Actual): December 28, 2009

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 16, 2005

Study Record Updates

• Last Update Posted (Actual): July 7, 2017
• Last Update Submitted That Met QC Criteria: June 6, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: GHLIQUID-1517; JapicCTI-050137 (Registry Identifier: JAPIC); JapicCTI-050132 (Registry Identifier: JAPIC); 2017-000914-47 (Registry Identifier: EudraCT)