Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2019-000844-81 | EudraCT Number |
Not provided
Not provided
Not provided
Unacceptable frequency of hypoglycemia observed at and above 200 ug/kg/day
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is an extension study to Tercica study MS301 (NCT00125164) and is intended to collect long term safety and efficacy data on the continued use of recombinant human insulin-like growth factor-1 (rh IGF-1) in children and adolescents treated for primary IGF-1 deficiency (IGFD). The secondary objective is to use the data collected to learn more about the relationship of IGF-1 exposure to the promotion of normal growth and pubertal development.
Primary IGFD is a term that has been used to describe patients with intrinsic cellular defects in GH action. In this protocol, subjects that have completed one year of mecasermin treatment on Tercica protocol MS301 (NCT00125164) will be allowed to enroll in this extension study. All subjects were planned to receive treatment.
This is a Phase IIIb open-label, multi-center, parallel dose, extension study conducted in approximately 40 centers across the United States.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All rhIGF-1 Subjects | Experimental | All subjects entering MS306 began recombinant human insulin-like growth factor-1 (rhIGF-1) twice a day (BID) treatment. Each subject treated in MS301 had an MS306 starting dose that was based on their dose at the completion of MS301 (i.e. subcutaneous injections of rhIGF-1 at 40, 80, or 120 micrograms [μg]/ kilogram [kg] BID). MS301 untreated control subjects were randomised in MS306 in a 1:1 ratio to a dose of either 80 or 120 μg/kg rhIGF-1 BID. Following Protocol Amendment 1, all subjects received either 80 or 120 μg/kg rhIGF-1 BID until the implementation of Protocol Amendment 2. Following Protocol Amendment 2, all subjects were first switched to receive subcutaneous injections of 160 μg/kg rhIGF-1 once a day (QD), followed by individual dose-escalation first to 200 μg/kg rhIGF-1 QD and subsequently to a targeted maximum dose of 240 μg/kg rhIGF-1 QD. Subjects were treated QD until the early termination of the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rh IGF-1 (mecasermin) | Drug | Patients from untreated arm for prior study MS301 (NCT00125164) were randomized to a dose of either 80 or 120 mcg/kg twice daily. For patients receiving active treatment in previous study MS 301 (NCT00125164), they started on a dose of 80 or 120 mcg/kg twice daily based on the dose reached at end of the previous study. Following a protocol amendment in May 2009, all patients were switched to once daily doses of 160 µg/kg, escalated to a targeted maximum dose of 240 µg/kg. |
| Measure | Description | Time Frame |
|---|---|---|
| Height Velocity During BID Dosing Period | Height was measured standing, without shoes, as the average of 3 measurements by the same observer identical technique with a Harpenden or other wall-mounted stadiometer at baseline and each study visit up to 3 years. Height velocity (during any interval of time (annualised) is computed as (height on date 2 - height on date 1)/(age on date 2 - age on date 1) where height is expressed as centimetres so that height velocity is expressed as centimetres per year (cm/yr). Height velocity is presented for subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). | At Years 1, 2 and 3 in BID dosing period. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Height Standard Deviation (SD) Score During BID Dosing Period | Height was measured standing, without shoes, as the average of 3 measurements by the same observer using identical technique with a Harpenden or other wall-mounted stadiometer at baseline and each study visit up to 3 years. Height SD score was determined using the National Center for Health Statistics 2000 data as provided by the Center for Disease Control. The SD score was calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child. Mean change from baseline in height SD score is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Sr Vice President, Clinical Development and Medical Affairs | Ipsen (formerly Tercica, Inc.) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ipsen | Paris | France |
As subjects entered MS306 whilst MS301 was continuing, dosages were adjusted in MS306 after MS301 data became available. Baseline study data for MS306 were taken from the data collected for Visit 9 (Month 12) of study MS301.
All subjects that completed study MS301 (NCT00125164) were eligible to enter this Phase 3b, open-label, extension study in prepubertal and pubertal male and female subjects with growth failure associated with primary insulin-like growth factor-1 deficiency (IGFD). This study (MS306) was terminated early by the sponsor on 01 December 2009.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | All rhIGF-1 Subjects | All subjects entering MS306 began recombinant human insulin-like growth factor-1 (rhIGF-1) twice a day (BID) treatment. Each subject treated in MS301 had an MS306 starting dose that was based on their dose at the completion of MS301 (i.e. subcutaneous injections of rhIGF-1 at 40, 80, or 120 micrograms [μg]/ kilogram [kg] BID). MS301 untreated control subjects were randomised in MS306 in a 1:1 ratio to a dose of either 80 or 120 μg/kg rhIGF-1 BID. Following Protocol Amendment 1, the dosing regimen was changed and all subjects received either 80 or 120 μg/kg rhIGF-1 BID until the implementation of Protocol Amendment 2. Following Protocol Amendment 2, all subjects were first switched to receive subcutaneous injections of 160 μg/kg rhIGF-1 once a day (QD), followed by individual dose-escalation first to 200 μg/kg rhIGF-1 QD and subsequently to a targeted maximum dose of 240 μg/kg rhIGF-1 QD. Subjects were treated QD until the early termination of the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BID Dosing Period |
|
| ||||||||||||||||||||||||
| QD Dosing Period |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All rhIGF-1 Subjects | All subjects entering MS306 began rhIGF-1 BID treatment. Each subject treated in MS301 had an MS306 starting dose that was based on their dose at the completion of MS301 (i.e. subcutaneous injections of rhIGF-1 at 40, 80, or 120 μg/kg BID). MS301 untreated control subjects were randomised in MS306 in a 1:1 ratio to a dose of either 80 or 120 μg/kg rhIGF-1 BID. Following Protocol Amendment 1, the dosing regimen was changed and all subjects received either 80 or 120 μg/kg rhIGF-1 BID until the implementation of Protocol Amendment 2. Following Protocol Amendment 2, all subjects were first switched to receive subcutaneous injections of 160 μg/kg rhIGF-1 QD, followed by individual dose-escalation first to 200 μg/kg rhIGF-1 QD and subsequently to a targeted maximum dose of 240 μg/kg rhIGF-1 QD. Subjects were treated QD until the early termination of the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Height Velocity During BID Dosing Period | Height was measured standing, without shoes, as the average of 3 measurements by the same observer identical technique with a Harpenden or other wall-mounted stadiometer at baseline and each study visit up to 3 years. Height velocity (during any interval of time (annualised) is computed as (height on date 2 - height on date 1)/(age on date 2 - age on date 1) where height is expressed as centimetres so that height velocity is expressed as centimetres per year (cm/yr). Height velocity is presented for subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). | The modified Intent-To-Treat (MITT) population included subjects from the ITT population who were randomised to 120 μg/kg rhIGF-1 BID (either in MS301 or MS306). The subjects in the 80 μg/kg group were not analysed for efficacy due to the variations in their dose regimen and the duration of the regimen. | Posted | Mean | Standard Deviation | cm/year | At Years 1, 2 and 3 in BID dosing period. |
|
Adverse events were collected for the overall study (including both the BID and QD dosing periods) from Day 1 until early termination of the study (up to 4 years, 3 months).
The safety population included all subjects who received at least one dose of study medication.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All rhIGF-1 Subjects | All subjects entering MS306 began recombinant human insulin-like growth factor-1 (rhIGF-1) BID treatment. Each subject treated in MS301 had an MS306 starting dose that was based on their dose at the completion of MS301 (i.e. subcutaneous injections of rhIGF-1 at 40, 80, or 120 μg/kg BID). MS301 untreated control subjects were randomised in MS306 in a 1:1 ratio to a dose of either 80 or 120 μg/kg rhIGF-1 BID. Following Protocol Amendment 1, all subjects received either 80 or 120 μg/kg rhIGF-1 BID until the implementation of Protocol Amendment 2. Following Protocol Amendment 2, all subjects were first switched to receive subcutaneous injections of 160 μg/kg rhIGF-1 QD, followed by individual dose-escalation first to 200 μg/kg rhIGF-1 QD and subsequently to a targeted maximum dose of 240 μg/kg rhIGF-1 QD. Subjects were treated QD until the early termination of the study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
The study was terminated by the sponsor due to an unacceptably high incidence of hypoglycaemia observed in approximately 50% of the subjects receiving 200 μg/kg rhIGF-1 or greater QD.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ipsen Medical Director | Ipsen | See email | clinical.trials@ipsen.com |
| ID | Term |
|---|---|
| D006130 | Growth Disorders |
| D004392 | Dwarfism |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000604197 | mecasermin |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| At baseline and Years 1, 2 and 3 in BID dosing period. |
| Mean Change From Baseline in Body Mass Index (BMI) SD Score During BID Dosing Period | BMI SD score was calculated using the National Center for Health Statistics 2000 data as provided by the Center for Disease Control. The SD score was calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child. Mean change from baseline in BMI SD score is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). | At baseline and Years 1, 2 and 3 in BID dosing period. |
| Mean Change From Baseline in Bone Age During BID Dosing Period | Radiographs of the left hand and wrist were taken on an approximately annual basis for determination of bone (skeletal) age. The films were sent to a central facility for standardised evaluation. Mean change from baseline in bone age is presented for all subjects completing each year of BID treatment (i.e. Year1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). | At baseline and Years 1, 2 and 3 in BID dosing period. |
| Mean Change From Baseline in Predicted Adult Height During BID Dosing Period | Predicted adult heights were estimated using the Roche-Wainer-Theissen method which takes into account changes in age, height and bone age. Mean change from baseline in predicted adult height is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). | At baseline and Years 1, 2 and 3 in BID dosing period. |
| Withdrawal by Subject |
|
| Sponsor's decision |
|
| Other |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| OG000 |
| 120 μg/kg rhIGF-1 BID (MITT Population) |
Subjects in the MITT population received 120 μg/kg rhIGF-1 BID and received the same dose throughout the BID phase of the study. |
|
|
| Secondary | Mean Change From Baseline in Height Standard Deviation (SD) Score During BID Dosing Period | Height was measured standing, without shoes, as the average of 3 measurements by the same observer using identical technique with a Harpenden or other wall-mounted stadiometer at baseline and each study visit up to 3 years. Height SD score was determined using the National Center for Health Statistics 2000 data as provided by the Center for Disease Control. The SD score was calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child. Mean change from baseline in height SD score is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). | The MITT population included subjects from the ITT population who were randomised to 120 μg/kg rhIGF-1 BID (either in MS301 or MS306). The subjects in the 80 μg/kg group were not analysed for efficacy due to the variations in their dose regimen and the duration of the regimen. | Posted | Mean | Standard Deviation | SD score/year | At baseline and Years 1, 2 and 3 in BID dosing period. |
|
|
|
| Secondary | Mean Change From Baseline in Body Mass Index (BMI) SD Score During BID Dosing Period | BMI SD score was calculated using the National Center for Health Statistics 2000 data as provided by the Center for Disease Control. The SD score was calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child. Mean change from baseline in BMI SD score is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). | The MITT population included subjects from the ITT population who were randomised to 120 μg/kg rhIGF-1 BID (either in MS301 or MS306). The subjects in the 80 μg/kg group were not analysed for efficacy due to the variations in their dose regimen and the duration of the regimen. | Posted | Mean | Standard Deviation | SD score/year | At baseline and Years 1, 2 and 3 in BID dosing period. |
|
|
|
| Secondary | Mean Change From Baseline in Bone Age During BID Dosing Period | Radiographs of the left hand and wrist were taken on an approximately annual basis for determination of bone (skeletal) age. The films were sent to a central facility for standardised evaluation. Mean change from baseline in bone age is presented for all subjects completing each year of BID treatment (i.e. Year1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). | The MITT population included subjects from the ITT population who were randomised to 120 μg/kg rhIGF-1 BID (either in MS301 or MS306). The subjects in the 80 μg/kg group were not analysed for efficacy due to the variations in their dose regimen and the duration of the regimen. | Posted | Mean | Standard Deviation | Years | At baseline and Years 1, 2 and 3 in BID dosing period. |
|
|
|
| Secondary | Mean Change From Baseline in Predicted Adult Height During BID Dosing Period | Predicted adult heights were estimated using the Roche-Wainer-Theissen method which takes into account changes in age, height and bone age. Mean change from baseline in predicted adult height is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]). | The MITT population included subjects from the ITT population who were randomised to 120 μg/kg rhIGF-1 BID (either in MS301 or MS306). The subjects in the 80 μg/kg group were not analysed for efficacy due to the variations in their dose regimen and the duration of the regimen. | Posted | Mean | Standard Deviation | cm | At baseline and Years 1, 2 and 3 in BID dosing period. |
|
|
|
| 0 |
| 114 |
| 6 |
| 114 |
| 107 |
| 114 |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Forearm Fracture | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Otitis Externa | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Arthropod Bite | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Blood Glucose Decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Ear Infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Ear Pain | Ear and labyrinth disorders | MedDRA (12.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Gastroenteritis Viral | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Influenza Like Illness | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Injection Site Bruising | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Injection Site Hypertrophy | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Molluscum Contagiosum | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Otitis Externa | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Otitis Media | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pharyngitis Streptococcal | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Pharyngolaryngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Seasonal Allergy | Immune system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Tonsillar Hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Viral Upper Respiratory Tract Infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
Each investigator may publish or report data from their own subjects. The trial data in aggregate are the property of Tercica, Inc. and may not be published without permission of Tercica, Inc. Tercica, Inc. will be the final arbitrator of issues relating to the publication or presentation of the aggregate data.
| D009140 | Musculoskeletal Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D004700 | Endocrine System Diseases |
|
| Year 3 |
|
|
|
| Year 3 |
|
|
|
| Year 3 |
|
|
|
| Year 3 |
|
|