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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).

Recruiting
Conditions
IGF1 Deficiency
Registration Number
NCT00903110
Lead Sponsor
Ipsen
Brief Summary

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.

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

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
500
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Incidence of SAEs (including AESI of neoplasia) and all AEs, targeted AEs, deaths and withdrawals due to AEs.During the treatment period up to 30 days after the last dose.

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.

Secondary Outcome Measures
NameTimeMethod
Incidence of special situations and concomitant medicationsDuring the treatment period an average of 5 years and within 5 years post-treatment
Modelisation to identify predictive factors of height SDS changeFrom baseline at least up to 5 years or until the final adult height is achieved.
Modelisation to identify predictive factors of bone age developmentFrom 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.
Modelisation to identify predictive factors of pubertal (Tanner) stageFrom baseline at least up to 5 years or until the final adult height is achieved
Changes in QoL assessment using EQ-5D in participant aged 4 and over.At baseline, at year one, at least up to 5 years, at Final Adult Height.

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.

Height velocityFrom baseline at least up to 5 years or until the final adult height is achieved.
Bone age developmentFrom baseline at least up to 5 years or until the final adult height is achieved
Biological assessment : baseline GH concentrations, IGF-1 levels, IGFBP-3 levels and binding proteins.Throughout study at least up to 5 years.
Incidence of SAEs (including AESI of neoplasia), targeted AEs, all AEs, deaths, withdrawals due to AEs, special situations and concomitant medicationsWithin 5 years post-treatment

In the overall population, and in the subset of children and adolescents exposed to Increlex® for at least 3 cumulative years excluding interruptions.

Changes in height Standard Deviation Score (SDS)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 velocityFrom baseline at least up to 5 years or until the final adult height is achieved
Dose of Increlex® administratedPeriodically assessed during the study until treatment stop at least up to 5 years.
Presence or absence of gene deletion/mutationThroughout study at least up to 5 years.

including: GH gene, IGF-1 gene, FGF, PTPN11, GHR, D3-GHR, STAT5b, ALS, SHOX, PAPPA2 and any other genetic tests performed.

Pubertal stageFrom baseline at least up to 5 years or until the final adult height is achieved.
Modelisation to identify predictive factors of FAHFrom baseline at least up to 5 years or until the final adult height is achieved
Duration of Increlex exposurePeriodically 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)).Periodically assessed during the study until treatment stop at least up to 5 years.

This analysis will support the description of the lowest effective dose

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)).Periodically assessed during the study until treatment stop at least up to 5 years.

This analysis will support the description of the lowest effective dose

Description of neoplasia (benign and malignant) and hypoglycaemiaWithin the first 3 years after treatment start, between 3 and 5 years and over 5 years.

Trial Locations

Locations (58)

Pole medical Bel'Air

🇫🇷

Mulhouse, France

Centre Hospitalier de Blois

🇫🇷

Blois, France

Hôpital Jean Verdier

🇫🇷

Bondy, France

Hôpital Femme Mère-Enfant

🇫🇷

Bron, France

Hôpital Estaing

🇫🇷

Clermont-Ferrand, France

Hôpital Timone Enfants

🇫🇷

Marseille, France

Hôpital Arnaud de Villeneuve

🇫🇷

Montpellier, France

GHR Mulhouse Sud-Alsace

🇫🇷

Mulhouse, France

CHU Lenval

🇫🇷

Nice, France

Hôpital Necker Enfants Malades

🇫🇷

Paris, France

Hôpital Kremlin Bicetre

🇫🇷

Paris, France

Hôpital des Enfants

🇫🇷

Toulouse, France

Birmingham Children's Hospital

🇬🇧

Birmingham, United Kingdom

Great Ormond Street Hospital

🇬🇧

London, United Kingdom

Karolinska Universitetssjukhuset

🇸🇪

Stockholm, Sweden

Hospital Sant Joan de Déu

🇪🇸

Barcelona, Spain

Hospital Univ. de Cruces

🇪🇸

Bilbao, Spain

Hospital Universitari Sant Joan de Reus

🇪🇸

Reus, Spain

Hospital Universitario y Politécnico La Fe

🇪🇸

Valencia, Spain

Leeds General Infirmary

🇬🇧

Leeds, United Kingdom

The Royal London Hospital

🇬🇧

London, United Kingdom

Royal Manchester Children's Hospital

🇬🇧

Manchester, United Kingdom

Linköping University Hospital

🇸🇪

Linkoping, Sweden

Royal Belfast Hospital for Sick Children

🇬🇧

Belfast, United Kingdom

Hospital Univ Vall d'Hebrón

🇪🇸

Barcelona, Spain

Hospital Parc Taulí de Sabadell

🇪🇸

Barcelona, Spain

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

University of Miami Leonard M Miller

🇺🇸

Miami, Florida, United States

University Of Miami Leonard M. Miller

🇺🇸

Miami, Florida, United States

D&H National Research Centers

🇺🇸

Miami, Florida, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

UT Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Children's Health Specialty Center West Plano

🇺🇸

Plano, Texas, United States

Salzkammergut-Klinik Vöcklabruck

🇦🇹

Vöcklabruck, Austria

Hôpital Amiens-Picardie

🇫🇷

Amiens, France

Hôpital de Cayenne

🇬🇫

Cayenne, French Guiana

Universitätsklinikum Erlangen Kinder- und Jugendklinik

🇩🇪

Erlangen, Germany

Universitätsklinikum Heidelberg Kinderheilkunde

🇩🇪

Heidelberg, Germany

Universitätskliniken des Saarlandes Kinderklinik

🇩🇪

Homburg, Germany

Klinikum der Otto von Guericke Universität

🇩🇪

Magdeburg, Germany

Klinikum Oldenburg

🇩🇪

Oldenburg, Germany

Diabetologia Pediatrica Azienda Ospedaliero-Universitaria

🇮🇹

Ancona, Italy

Ospedale di Bolzano

🇮🇹

Bolzano, Italy

Spedali Civili di Brescia

🇮🇹

Brescia, Italy

Azienda ospedaliera universitaria Meyer

🇮🇹

Firenze, Italy

I.R.C.C.S. Giannina Gaslini

🇮🇹

Genova, Italy

U.O. Pediatria e Neonatologia Ospedale di Macerata

🇮🇹

Macerata, Italy

Azienda Ospedaliera Universitaria II

🇮🇹

Naples, Italy

Azienda Ospedaliera-Universitaria di Parma

🇮🇹

Parma, Italy

Azienda USL-IRCCS

🇮🇹

Reggio Emilia, Italy

Ospedale Pediatrico Bambino Gesù

🇮🇹

Roma, Italy

Hôpital Pierre Zobda Quitman

🇲🇶

Fort-de-France, Martinique

Samodzielny Publiczny Dzieciecy Szpital Kliniczny

🇵🇱

Białystok, Poland

Uniwersyteckie Centrum Kliniczne

🇵🇱

Gdańsk, Poland

Uniwersytecki Szpital Dziecięcy w Lublinie

🇵🇱

Lublin, Poland

Szpital kliniczny im. Karola Jonschnera

🇵🇱

Poznań, Poland

Kliniczny Szpital Wojewódzki

🇵🇱

Rzeszów, Poland

Pomeranian Medical University

🇵🇱

Szczecin, Poland

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