Long-term Safety Follow-up After Growth Hormone Treatment of Short Children Born Small for Gestational Age (SGA)

Long-term Safety Follow-up After Growth Hormone Treatment (rhGH) of Short Children Born Small for Gestational Age (SGA)

This study is performed as part of the Marketing Authorisation Holder's post-marketing pharmacovigilance plan to investigate the long-term safety, in particular the diabetogenic potential and immunogenicity of rhGH therapy in short children born small for gestational age (SGA).

Study Overview

• Status: Terminated
• Conditions: Short Children Born Small for Gestational Age (SGA)
• Intervention / Treatment: Other: Bloodsampling

Detailed Description

The purpose of this study is

1. to monitor short children born SGA who were treated with growth hormone in study EP00-401 for the development of diabetes for a further 10 years after termination of growth hormone treatment

   and

2. to report the incidence of anti-rhGH antibodies and of E. coli host cell peptide (HCP) antibodies (ABs) for 6 months after termination of GH treatment.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Novartis Investigative Site
  • Praha 5, Czechia, 150 06
    • Novartis Investigative Site
  • Czech Republic
    • Usti nad Labem, Czech Republic, Czechia, 400 11
      • Novartis Investigative Site
• Georgia
  • Tbilisi, Georgia, 144
    • Novartis Investigative Site
• Germany
  • Muenchen, Germany, 80337
    • Novartis Investigative Site
  • Sankt Augustin
    • Nordrhein Westfalen, Sankt Augustin, Germany, 53757
      • Novartis Investigative Site
• Hungary
  • Miskolc, Hungary, 3526
    • Novartis Investigative Site
• Poland
  • Gdansk, Poland, 80 952
    • Novartis Investigative Site
  • Krakow, Poland, 30-663
    • Novartis Investigative Site
  • Lodz, Poland, 93-338
    • Novartis Investigative Site
  • Szczecin, Poland, 71-252
    • Novartis Investigative Site
  • Warszawa, Poland, 04 730
    • Novartis Investigative Site
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-311
      • Novartis Investigative Site
    • Wrocław, Dolnoslaskie, Poland, 50-368
      • Novartis Investigative Site
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85667
      • Novartis Investigative Site
  • Podkarpackie
    • Rzeszow, Podkarpackie, Poland, 35-301
      • Novartis Investigative Site
  • Slaskie
    • Katowice, Slaskie, Poland, 40-752
      • Novartis Investigative Site
    • Zabrze, Slaskie, Poland, 41-800
      • Novartis Investigative Site
  • Swietokrzyskie
    • Kielce, Swietokrzyskie, Poland, 25734
      • Novartis Investigative Site
  • Wielkopolskie
    • Poznai, Wielkopolskie, Poland, 60-572
      • Novartis Investigative Site
• Romania
  • Bucuresti, Romania, 20395
    • Novartis Investigative Site
  • Cluj Napoca, Romania, CLUJ
    • Novartis Investigative Site
  • Iasi
    • Lasi, Iasi, Romania, 700111
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients who fulfilled the diagnosis SGA, participated in study EP00-401, and received at least one dose of study medication
• Written informed consent of patient (for children who can read and/ or understand) and/or parent or legal guardian

Exclusion Criteria:

• Patients unwilling and/or parents/guardians who are not capable of ensuring compliance with the provisions of the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Monitoring of long-term safety; Long-term safety follow-up after the end of treatment with Omnitrope (single arm)	Other: Bloodsampling; Bloodsampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Long-term Effect of Growth Hormone Treatment on the Development of Diabetes After End of Therapy.	Number of participants diagnosed with Diabetes mellitus type 2 during the study, defined as fullfilment of these 3 criteria: FPG ≥ 126 mg/dl (7.0 mmol/L) during blood sampling and/or during Oral Glucose Tolerance Test (OGTT); 2-h plasma glucose ≥ 200 mg/dl (11.1 mmol/L) during an OGTT; Investigator documenting diagnosis of diabetes mellitus type 2 during OGTT	5 years
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Plasma Glucose (FPG) Levels	Supportive to Primary Endpoint	baseline, 6 months, 1 year, 5 years
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Fasting Insulin Levels	Supportive to Primary Endpoint	baseline, 6 months, 1 year, 5 years
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through Glucose Glycolsylated Hemoglobin (HbA1c)	Supportive to Primary Endpoint	baseline, 6 months, 1 year, 5 years
To Evaluate the Long Term Effects of rhGH on Carbohydrate Metabolism Through HOMA and QUICKI Scores	Supportive to Primary Endpoint. HOMA = homeostasis model assessment for Insulin resistance: Healthy Range: 1.0 (0.5-1.4). < 1.0 means you are insulin-sensitive which is optimal. >1.9 indicates early insulin resistance. > 2.9 indicates significant insulin resistance. The quantitative insulin sensitivity check index (QUICKI) measures insulin sensitivity, which is the inverse of insulin resistance. The QUICKI calculation for insulin resistance in humans fall broadly within a range between 0.45 for unusually healthy individuals and 0.30 in diabetics. Lower numbers reflect greater insulin resistance.	baseline, 6 months, 1 year, 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to Evaluate IGF-I and IGFBP-3 Levels After End of Growth Hormone Treatment		baseline, 6 months, 1 year , 5 years
To Evaluate the Incidence of Anti-rhGH Antibodies After Termination of Growth Hormone Treatment.	number of participants with positive results for anti-drug antibody (ADA). Percentages indicated are calculated based on the total number of patients (118 participants).	baseline, 6 months, 1 year, 5 years
to Evaluate Final Height		baseline, 6 months, 1 year, 5 years

Collaborators and Investigators

• Sponsor: Sandoz
• Investigators: Study Chair: Sandoz Biopharmaceuticals Sandoz, Sandoz GmbH

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 20, 2009
• Primary Completion (ACTUAL): October 31, 2018
• Study Completion (ACTUAL): October 31, 2018

Study Registration Dates

• First Submitted: December 12, 2011
• First Submitted That Met QC Criteria: December 13, 2011
• First Posted (ESTIMATE): December 14, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 14, 2019
• Last Update Submitted That Met QC Criteria: July 17, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: safety; follow-up; Long-term; growth hormone treatment; Somatropin; Small for Gestational Age; short children
• Other Study ID Numbers: CEP00-402

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No