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).

IGF1 Deficiency Clinical Trial

Official title:

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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00903110
• Other study ID #: 2-79-52800-002
• Secondary ID: EUPAS7708
• Status: Recruiting
• Start date: December 9, 2008
• Est. completion date: December 31, 2027

Study information

• Verified date: May 2024
• Source: Ipsen
• Contact: Ipsen Recruitment Enquiries
• Email: clinical.trials[@]ipsen.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• IGF1 Deficiency

Intervention

Drug:
• Increlex®
Increlex® (mecasermin [rDNA origin] injection), 10 mg/ml solution for injection, 40-120mcg/kg BID or 0,04 to 0,12 mg/kg BID, as prescribed by physician

Locations

Country	Name	City	State
Austria	Salzkammergut-Klinik Vöcklabruck	Vöcklabruck
France	Hôpital Amiens-Picardie	Amiens
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 Kremlin Bicetre	Paris
France	Hôpital Necker Enfants Malades	Paris
France	Hôpital des Enfants	Toulouse
French Guiana	Hôpital de Cayenne	Cayenne
Germany	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
Italy	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
Martinique	Hôpital Pierre Zobda Quitman	Fort-de-France
Poland	Samodzielny Publiczny Dzieciecy Szpital Kliniczny	Bialystok
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Uniwersytecki Szpital Dzieciecy w Lublinie	Lublin
Poland	Szpital kliniczny im. Karola Jonschnera	Poznan
Poland	Kliniczny Szpital Wojewódzki	Rzeszów
Poland	Pomeranian Medical University	Szczecin
Spain	Hospital Parc Taulí de Sabadell	Barcelona
Spain	Hospital Sant Joan de Déu	Barcelona
Spain	Hospital Univ Vall d'Hebrón	Barcelona
Spain	Hospital Univ. de Cruces	Bilbao
Spain	Hospital Universitari Sant Joan de Reus	Reus
Spain	Hospital Universitario y Politécnico La Fe	Valencia
Sweden	Linköping University Hospital	Linkoping
Sweden	Karolinska Universitetssjukhuset	Stockholm
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	The Royal London Hospital	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	D&H National Research Centers	Miami	Florida
United States	University of Miami Leonard M Miller	Miami	Florida
United States	University Of Miami Leonard M. Miller	Miami	Florida
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Health Specialty Center West Plano	Plano	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

United States,  Austria,  France,  French Guiana,  Germany,  Italy,  Martinique,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Incidence of special situations and concomitant medications		During the treatment period an average of 5 years and within 5 years post-treatment
Secondary	Changes in height Standard Deviation Score (SDS)		From baseline at least up to 5 years or until the final adult height is achieved.
Secondary	Height velocity		From baseline at least up to 5 years or until the final adult height is achieved.
Secondary	Bone age development		From baseline at least up to 5 years or until the final adult height is achieved
Secondary	Body mass index (BMI)		From baseline at least up to 5 years or until the final adult height is achieved.
Secondary	Pubertal stage		From baseline at least up to 5 years or until the final adult height is achieved.
Secondary	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.
Secondary	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.
Secondary	Modelisation to identify predictive factors of Height velocity		From baseline at least up to 5 years or until the final adult height is achieved
Secondary	Modelisation to identify predictive factors of FAH		From baseline at least up to 5 years or until the final adult height is achieved
Secondary	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
Secondary	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
Secondary	Dose of Increlex® administrated		Periodically assessed during the study until treatment stop at least up to 5 years.
Secondary	Duration of Increlex exposure		Periodically assessed during the study until treatment stop at least up to 5 years.
Secondary	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.
Secondary	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.
Secondary	Biological assessment : baseline GH concentrations, IGF-1 levels, IGFBP-3 levels and binding proteins.		Throughout study at least up to 5 years.
Secondary	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.
Secondary	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.
Secondary	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.