Global Patient Registry to Monitor Long-term Safety and Effectiveness of Increlex® in Children and Adolescents With Severe Primary Insulin-like Growth Factor-1 Deficiency (SPIGFD).

The Increlex® Global Registry is a descriptive, multicenter, observational, prospective, open-ended, non interventional, post-authorisation surveillance registry.

The main purpose of this global registry is to collect, analyse and report safety data during and up to at least 5 years after the end of treatment in children and adolescents receiving Increlex® therapy for SPIGFD according to the locally approved product information.

Study Overview

• Status: Recruiting
• Conditions: IGF1 Deficiency
• Intervention / Treatment: Drug: Increlex®

Detailed Description

This registry is a Post-Authorisation Safety Study called the Increlex® Global Registry which is intended primarily to monitor the safety of Increlex® therapy in children and adolescents with Severe Primary IGF-1 Deficiency and secondly to follow the effectiveness of this treatment. Patients who have already started Increlex® therapy before entering this registry may be included and data will be collected retrospectively.

The countries participating in this registry are Austria, France, Germany, Italy, Poland, Spain, Sweden, United Kingdom and the USA

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Ipsen Recruitment Enquiries; Email: clinical.trials@ipsen.com

Study Locations

• Austria
  • Vöcklabruck, Austria, A-4840
    • Recruiting
    • Salzkammergut-Klinik Vöcklabruck
• France
  • Amiens, France, 80080
    • Terminated
    • Hôpital Amiens-Picardie
  • Blois, France, 41000
    • Recruiting
    • Centre Hospitalier de Blois
  • Bondy, France, 93140
    • Recruiting
    • Hôpital Jean Verdier
  • Bron, France, 69500
    • Recruiting
    • Hôpital Femme Mère-Enfant
  • Clermont-Ferrand, France, 63100
    • Recruiting
    • Hôpital Estaing
  • Marseille, France, 13005
    • Recruiting
    • Hôpital Timone Enfants
  • Montpellier, France, 34090
    • Recruiting
    • Hopital Arnaud de Villeneuve
  • Mulhouse, France
    • Terminated
    • GHR Mulhouse Sud-Alsace
  • Nice, France, 06200
    • Withdrawn
    • CHU Lenval
  • Paris, France, 75015
    • Recruiting
    • Hopital Necker Enfants Malades
  • Paris, France, 97270
    • Recruiting
    • Hôpital Kremlin Bicêtre
  • Toulouse, France, 31300
    • Recruiting
    • Hopital des Enfants
• French Guiana
  • Cayenne, French Guiana, 97306
    • Withdrawn
    • Hôpital de Cayenne
• Germany
  • Erlangen, Germany, 91054
    • Recruiting
    • Universitätsklinikum Erlangen Kinder- und Jugendklinik
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitätsklinikum Heidelberg Kinderheilkunde
  • Homburg, Germany, 66424
    • Recruiting
    • Universitätskliniken des Saarlandes Kinderklinik
  • Magdeburg, Germany, 39120
    • Recruiting
    • Klinikum der Otto von Guericke Universität
  • Oldenburg, Germany, 26133
    • Recruiting
    • Klinikum Oldenburg
• Italy
  • Ancona, Italy
    • Not yet recruiting
    • Diabetologia Pediatrica Azienda Ospedaliero-Universitaria
  • Bolzano, Italy, 39100
    • Recruiting
    • Ospedale di Bolzano
  • Brescia, Italy, 25100
    • Recruiting
    • Spedali Civili di Brescia
  • Firenze, Italy, 50139
    • Not yet recruiting
    • Azienda ospedaliera universitaria Meyer
  • Genova, Italy, 16147
    • Recruiting
    • I.R.C.C.S. Giannina Gaslini
  • Macerata, Italy
    • Terminated
    • U.O. Pediatria e Neonatologia Ospedale di Macerata
  • Naples, Italy, 80138
    • Not yet recruiting
    • Azienda Ospedaliera Universitaria II
  • Reggio Emilia, Italy
    • Recruiting
    • Azienda USL-IRCCS
  • Roma, Italy, 00165
    • Recruiting
    • Ospedale Pediatrico Bambino Gesu
• Martinique
  • Fort-de-France, Martinique, 97200
    • Recruiting
    • Hôpital Pierre Zobda Quitman
    • Contact: Z
• Poland
  • Białystok, Poland, 15-274
    • Recruiting
    • Samodzielny Publiczny Dzieciecy Szpital Kliniczny
  • Gdańsk, Poland, 80-294
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Lublin, Poland, 20-093
    • Recruiting
    • Uniwersytecki Szpital Dziecięcy w Lublinie
  • Poznań, Poland, 60-572
    • Recruiting
    • Szpital kliniczny im. Karola Jonschnera
  • Rzeszów, Poland, 35-301
    • Recruiting
    • Kliniczny Szpital Wojewódzki
  • Szczecin, Poland
    • Recruiting
    • Pomeranian Medical University
• Spain
  • Barcelona, Spain, 08950
    • Recruiting
    • Hospital Sant Joan de Déu
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Univ Vall d'Hebrón
  • Barcelona, Spain, 08208
    • Recruiting
    • Hospital Parc Taulí de Sabadell
  • Bilbao, Spain, 48903
    • Recruiting
    • Hospital Univ. de Cruces
  • Reus, Spain, 43204
    • Recruiting
    • Hospital Universitari Sant Joan de Reus
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario y Politecnico La Fe
• Sweden
  • Linkoping, Sweden, 57850
    • Recruiting
    • Linköping University Hospital
  • Stockholm, Sweden, 17176
    • Recruiting
    • Karolinska Universitetssjukhuset
• United Kingdom
  • Belfast, United Kingdom, BT12 6BA
    • Recruiting
    • Royal Belfast Hospital for Sick Children
  • Birmingham, United Kingdom, B4 6NH
    • Terminated
    • Birmingham Children's Hospital
  • Leeds, United Kingdom, LS1 3EX
    • Not yet recruiting
    • Leeds General Infirmary
  • London, United Kingdom, WC1N 3JH
    • Recruiting
    • Great Ormond Street Hospital
  • London, United Kingdom, E1 1FR
    • Recruiting
    • The Royal London Hospital
  • Manchester, United Kingdom, M13 0JH
    • Terminated
    • Royal Manchester Children's Hospital
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Children's Hospital of Orange County
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University Of Miami Leonard M. Miller
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Leonard M Miller
    • Miami, Florida, United States, 33155
      • Withdrawn
      • D&H National Research Centers
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Not yet recruiting
      • UT Southwestern Medical Center
    • Plano, Texas, United States, 75093
      • Withdrawn
      • Children's Health Specialty Center West Plano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children and adolescents with Growth Failure due to Severe Primary IGF-1 Deficiency

Description

Inclusion Criteria:

• For US : patients starting or planning to start or currently receiving treatment with Increlex® therapy for severe primary IGF-1 deficiency as defined by the US Increlex® prescribing information or for growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.For EU : patients starting or planning to start or currently receiving treatment with Increlex® therapy according to the locally approved product information.
• Parents or legally authorized representatives if applicable must give signed informed consent before any registry-related activities are conducted. Assent from the subject should also be obtained as appropriate

Exclusion Criteria:

• Subject currently participating in an Increlex® clinical trial
• Subject currently participating in any clinical trial for growth retardation
• Patient with any contraindication to Increlex® or any condition subject to special warning as per the locally approved label
• For US patients, these include patients with hypersensitivity to the active substance or any of the excipients, patients with active or suspected neoplasia and patients with closed epiphyses.
• For EU patients: these include patients with hypersensitivity to the active substance or any of the excipients, patients with active or suspected neoplasia or any condition or medical history which increases the risk of benign or malignant neoplasia and patients with closed epiphyses

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of SAEs (including AESI of neoplasia) and all AEs, targeted AEs, deaths and withdrawals due to AEs.	Targeted AE includes hypersensitivity; scoliosis; immunogenicity (presence of antibodies if available); slipped capital femoral epiphysis, headache, otitis media, papilloedema, hypoglycaemia (suspected or documented - documented means blood level glucose < 50 mg/dL or 2.78 mmol/L), acromegalic facial changes, gynaecomastia, hearing loss, intracranial hypertension, lipohypertrophy at injection sites, sleep apnoea, tonsillar hypertrophy, cardiomegaly, oedema and myalgia.	During the treatment period up to 30 days after the last dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of SAEs (including AESI of neoplasia), targeted AEs, all AEs, deaths, withdrawals due to AEs, special situations and concomitant medications	In the overall population, and in the subset of children and adolescents exposed to Increlex® for at least 3 cumulative years excluding interruptions.	Within 5 years post-treatment
Incidence of special situations and concomitant medications		During the treatment period an average of 5 years and within 5 years post-treatment
Changes in height Standard Deviation Score (SDS)		From baseline at least up to 5 years or until the final adult height is achieved.
Height velocity		From baseline at least up to 5 years or until the final adult height is achieved.
Bone age development		From baseline at least up to 5 years or until the final adult height is achieved
Body mass index (BMI)		From baseline at least up to 5 years or until the final adult height is achieved.
Pubertal stage		From baseline at least up to 5 years or until the final adult height is achieved.
Estimation of differences between predicted adult height (PAH) and final adult height (FAH)		From baseline at least up to 5 years or until the final adult height is achieved.
Modelisation to identify predictive factors of height SDS change		From baseline at least up to 5 years or until the final adult height is achieved.
Modelisation to identify predictive factors of Height velocity		From baseline at least up to 5 years or until the final adult height is achieved
Modelisation to identify predictive factors of FAH		From baseline at least up to 5 years or until the final adult height is achieved
Modelisation to identify predictive factors of pubertal (Tanner) stage		From baseline at least up to 5 years or until the final adult height is achieved
Modelisation to identify predictive factors of bone age development		From baseline at least up to 5 years or until the final adult height is achieved
Dose of Increlex® administrated		Periodically assessed during the study until treatment stop at least up to 5 years.
Duration of Increlex exposure		Periodically assessed during the study until treatment stop at least up to 5 years.
Description of effectiveness parameters height SDS according to average dose received and according to dose ranges (e.g. 4 dose ranges (≤50, ]50-80], ]80-110], > 110 μg/kg BID)).	This analysis will support the description of the lowest effective dose	Periodically assessed during the study until treatment stop at least up to 5 years.
Description of effectiveness parameters height velocity according to average dose received and according to dose ranges (e.g. 4 dose ranges (≤50, ]50-80], ]80-110], > 110 μg/kg BID)).	This analysis will support the description of the lowest effective dose	Periodically assessed during the study until treatment stop at least up to 5 years.
Biological assessment : baseline GH concentrations, IGF-1 levels, IGFBP-3 levels and binding proteins.		Throughout study at least up to 5 years.
Presence or absence of gene deletion/mutation	including: GH gene, IGF-1 gene, FGF, PTPN11, GHR, D3-GHR, STAT5b, ALS, SHOX, PAPPA2 and any other genetic tests performed.	Throughout study at least up to 5 years.
Changes in QoL assessment using EQ-5D in participant aged 4 and over.	The QoL will be assessed using the EQ-5D-Y paediatric questionnaire. The 5 domains and VAS will be described at each timepoint as well as the evolution from baseline.	At baseline, at year one, at least up to 5 years, at Final Adult Height.
Description of neoplasia (benign and malignant) and hypoglycaemia		Within the first 3 years after treatment start, between 3 and 5 years and over 5 years.

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Publications and helpful links

General Publications

• Bang P, Polak M, Perrot V, Sert C, Shaikh H, Woelfle J. Pubertal Timing and Growth Dynamics in Children With Severe Primary IGF-1 Deficiency: Results From the European Increlex(R) Growth Forum Database Registry. Front Endocrinol (Lausanne). 2022 Feb 18;13:812568. doi: 10.3389/fendo.2022.812568. eCollection 2022.
• Bang P, Woelfle J, Perrot V, Sert C, Polak M. Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndrome. Eur J Endocrinol. 2021 Feb;184(2):267-276. doi: 10.1530/EJE-20-0325.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2008
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 30, 2009
• First Submitted That Met QC Criteria: May 14, 2009
• First Posted (Estimated): May 15, 2009

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Growth Substances; Mecasermin
• Other Study ID Numbers: 2-79-52800-002; EUPAS7708 (Other Identifier: EU PAS Register)