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The trial will compare a twice-monthly somavaratan dosing regimen for non-inferiority of treatment effect against daily injections of rhGH.
This study is designed as a pivotal study to compare the safety and efficacy of a selected dose regimen of somavaratan to daily rhGH. The study is a randomized, multi-center, open label study of 12 months duration. The primary endpoint is height velocity at 12 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Somavaratan | Experimental | Participants will receive somavaratan 3.5 milligrams (mg)/kilogram (kg) subcutaneous (SC) bolus injection twice monthly for 12 months. |
|
| rhGH | Active Comparator | Participants will receive commercially available rhGH (genotropin) 34 micrograms (μg)/kg once daily SC bolus injection for 12 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Somavaratan | Drug | Somavaratan will be administered per dose and schedule specified in the arm description. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Annual Height Velocity | Height measured without shoes in triplicate by stadiometer. Annual height velocity was calculated as (height at Month 12 - height at Baseline)/(Month 12 Date - Baseline Date) * 365.25, where height was expressed as centimeters (cm) so that height velocity is expressed as centimeters per year (cm/yr). Annual height velocity after 12 months continuous treatment with either somavaratan or daily rhGH has been reported. Missing data was imputed using last observation carried forward. Least square (LS) mean was calculated using analysis of covariance (ANCOVA) model. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Height Standard Deviation Score (SDS) at Month 12 | Height SDS was determined using the Center for Disease Control (CDC) Clinical Growth Charts; 2000. The SD score was calculated as the participant's height value minus the mean divided by the standard deviation (SD). The mean and the SD vary depending on the age and sex of the participant. Mean change from baseline in height SDS at Month 12 is presented. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Will Charlton, MD | Sponsor GmbH | Study Director |
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Participants were stratified by region (North America and Europe), age (above and below anticipated median age of 7.5 years) and baseline Insulin-like growth factor-I (IGF-I) standard deviation score (SDS) (above and below anticipated median of -1.7) and randomized in a 3:1 ratio to receive either somavaratan or recombinant human growth hormone (rhGH).
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| ID | Title | Description |
|---|---|---|
| FG000 | Somavaratan | Participants received somavaratan 3.5 milligrams (mg)/kilogram (kg) subcutaneous (SC) bolus injection twice monthly for 12 months. |
| FG001 | rhGH | Participants received commercially available rhGH (genotropin) 34 micrograms (μg)/kg once daily SC bolus injection for 12 months. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population included all participants who received any amount of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Somavaratan | Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months. |
| BG001 | rhGH | Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months. |
| 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 | Annual Height Velocity | Height measured without shoes in triplicate by stadiometer. Annual height velocity was calculated as (height at Month 12 - height at Baseline)/(Month 12 Date - Baseline Date) * 365.25, where height was expressed as centimeters (cm) so that height velocity is expressed as centimeters per year (cm/yr). Annual height velocity after 12 months continuous treatment with either somavaratan or daily rhGH has been reported. Missing data was imputed using last observation carried forward. Least square (LS) mean was calculated using analysis of covariance (ANCOVA) model. | ITT population included all randomized participants. | Posted | Least Squares Mean | Standard Error | cm/year | 12 months |
|
Baseline up to Month 12
Safety population included all participants who received any amount of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Somavaratan | Participants received somavaratan 3.5 mg/kg SC bolus injection twice monthly for 12 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arnold-Chiari malformation | Congenital, familial and genetic disorders | MedDRA 20 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA 20 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Operating Officer | Aravive, Inc. | (936) 355-1910 | clinicaltrials@aravive.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 5, 2017 | Nov 21, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 5, 2017 | Nov 21, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006130 | Growth Disorders |
| D004393 | Dwarfism, Pituitary |
| D005183 | Failure to Thrive |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004392 | Dwarfism |
| D001848 | Bone Diseases, Developmental |
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| rhGH | Drug | rhGH will be administered per dose and schedule specified in the arm description. |
|
|
| Baseline, Month 12 |
| Change From Baseline in Bone Age Relative to Chronological Age at Month 12, as Assessed by Central Reader | Bone age was assessed from a radiograph of the left hand and wrist by central reader. | Baseline, Month 12 |
| Change From Baseline in Body Mass Index (BMI) at Month 12 | The BMI is a person's weight in kilograms (kg) divided by the square of height in meters. | Baseline, Month 12 |
| Change From Baseline in Body Weight at Month 12 | Body weight measured in light clothing and without shoes. | Baseline, Month 12 |
| Change From Baseline in Insulin-like Growth Factor 1 (IGF-I) SDS at Month 12 | The SD score was calculated as the actual value of IGF-I minus mean reference value of IGF-1 divided by reference standard deviation of IGF-I. The mean and the SD vary depending on the age and sex of the participant. Change in IGF-I level (SD score) at Month 12 from Baseline was assessed. A higher score reflects a better outcome. | Baseline, Month 12 |
| Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) at Month 12 | Baseline, Month 12 |
| Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. | Baseline up to Month 12 |
| Non-compliance With Study Drug |
|
| Withdrawal by Subject |
|
| Poor Growth |
|
| Randomized but not treated |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | rhGH | Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months. |
|
|
|
| Secondary | Change From Baseline in Height Standard Deviation Score (SDS) at Month 12 | Height SDS was determined using the Center for Disease Control (CDC) Clinical Growth Charts; 2000. The SD score was calculated as the participant's height value minus the mean divided by the standard deviation (SD). The mean and the SD vary depending on the age and sex of the participant. Mean change from baseline in height SDS at Month 12 is presented. | ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | SD score | Baseline, Month 12 |
|
|
|
| Secondary | Change From Baseline in Bone Age Relative to Chronological Age at Month 12, as Assessed by Central Reader | Bone age was assessed from a radiograph of the left hand and wrist by central reader. | ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | months | Baseline, Month 12 |
|
|
|
| Secondary | Change From Baseline in Body Mass Index (BMI) at Month 12 | The BMI is a person's weight in kilograms (kg) divided by the square of height in meters. | ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | kg/m^2 | Baseline, Month 12 |
|
|
|
| Secondary | Change From Baseline in Body Weight at Month 12 | Body weight measured in light clothing and without shoes. | ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | kg | Baseline, Month 12 |
|
|
|
| Secondary | Change From Baseline in Insulin-like Growth Factor 1 (IGF-I) SDS at Month 12 | The SD score was calculated as the actual value of IGF-I minus mean reference value of IGF-1 divided by reference standard deviation of IGF-I. The mean and the SD vary depending on the age and sex of the participant. Change in IGF-I level (SD score) at Month 12 from Baseline was assessed. A higher score reflects a better outcome. | ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | SD score | Baseline, Month 12 |
|
|
|
| Secondary | Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) at Month 12 | ITT population included all randomized participants. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Median | Standard Deviation | nanomoles (nmol)/milliliter (mL) | Baseline, Month 12 |
|
|
|
| Secondary | Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. | Safety population included all participants who received any amount of study drug. | Posted | Count of Participants | Participants | Baseline up to Month 12 |
|
|
|
| 0 |
| 104 |
| 6 |
| 104 |
| 59 |
| 104 |
| EG001 | rhGH | Participants received commercially available rhGH (genotropin) 34 μg/kg once daily SC bolus injection for 12 months. | 0 | 32 | 0 | 32 | 16 | 32 |
| Adrenal insufficiency | Endocrine disorders | MedDRA 20 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 20 | Systematic Assessment |
|
| Syringomyelia | Nervous system disorders | MedDRA 20 | Systematic Assessment |
|
| Glomerulonephritis | Renal and urinary disorders | MedDRA 20 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 20 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 20 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA 20 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20 | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA 20 | Systematic Assessment |
|
| Injection site haematoma | General disorders | MedDRA 20 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20 | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA 20 | Systematic Assessment |
|
US Sites:
Institution shall cause Principal Investigator to submit a complete copy of the proposed publication to Sponsor at least 60 days prior to presentation or submission to any third party.
Non-US sites:
The Investigator and the Institution agree that any proposed publication relating to the research and/or Study conducted under this Agreement will be submitted to Sponsor for review at least 90 days prior to submission for publication.
Additional agreement conditions apply.
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D001849 | Bone Diseases, Endocrine |
| D007018 | Hypopituitarism |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
| D012816 | Signs and Symptoms |