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Phase 3 clinical trial of somavaratan in pediatric growth hormone deficiency (PGHD) did not meet its primary endpoint of non-inferiority.
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Open-label extension study to evaluate the safety of long-term twice-monthly administration of somavaratan in adults with Growth Hormone Deficiency (GHD).
An open-label extension study to evaluate the safety of long-term twice-monthly administration of somavaratan in adults with GHD. This multicenter study is open to participants completing a Versartis adult GHD study as well as approximately 40 new somavaratan naïve participants (either recombinant human growth hormone [rhGH] treatment naïve or currently receiving daily rhGH therapy). All participants will receive twice-monthly (every 15 days ± 2 days) subcutaneous (SC) somavaratan. Doses will be titrated to each participant's individual insulin-like growth factor-I (IGF-I) responses based on the IGF-I level 7 days post-dose until a maintenance dose is achieved. Participants receiving somavaratan in a previous somavaratan study will have their dose decreased by half (minimum dose of 20 milligrams [mg], 40 mg for women on estrogen, rounded down to the nearest even number) and will be titrated per the Dose Titration Plan. New participants enrolling in this study will be assigned to one of two cohorts based on sensitivity to rhGH and titrated per the Dose Titration Plan.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Somavaratan | Experimental | Long-acting recombinant human growth hormone therapy administered subcutaneously twice-monthly in adult participants with GHD |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| somavaratan | Drug | Long-acting recombinant human growth hormone therapy administered subcutaneously twice-monthly |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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'. | From first dose of study drug up to approximately 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Average Dose Level During Titration/Maintenance | Total average dose received by a participant during titration/maintenance has been reported. | Up to Month 12 |
| Number of Participants With Dose Adjustments |
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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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The study was open to participants completing a Versartis adult growth hormone deficiency (GHD) study (15VR7 [NCT02526420]) as well as new somavaratan naïve participants (either recombinant human growth hormone [rhGH] treatment naïve or receiving daily rhGH therapy).
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| ID | Title | Description |
|---|---|---|
| FG000 | Somavaratan | Participants received once-monthly subcutaneous (SC) somavaratan per Protocol Version 1.0. The dosing regimen was then modified in Protocol Version 2.0 to twice-monthly SC somavaratan. Doses were titrated to each participant's individual IGF-I responses based on the insulin-like growth factor-I (IGF-I) level 7 days postdose until a maintenance dose was achieved. Maintenance dose was defined as an IGF-I value between 0 and 2.0 standard deviation score (SDS) for two consecutive 7-day postdose time points (Day 8, peak level). Participants who received somavaratan once-monthly in this study or in a previous somavaratan study (15VR7), had their dose decreased by half (minimum dose of 20 milligrams [mg], 40 mg for women on estrogen, rounded down to the nearest even number) and were titrated based on IGF-I level at Day 8. New participants enrolling in this study received a starting dose of 20 mg twice-monthly (40 mg for women on estrogen) and were titrated based on IGF-I level at Day 8. Maintenance doses were adjusted further based on pharmacodynamic (PD) data at the discretion of the Investigator or Medical Monitor. The maximum allowable dose of somavaratan was 250.0 mg. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 30, 2016 |
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The number of participants with a dose adjustment (titrated up/down) at each month are summarized.
| Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 |
| Number of Participants Who Were Anti-drug Antibody (ADA) Positive | Up to approximately 2 years |
| Number of Participants With Positive Neutralizing Antibodies (NABs) | Up to approximately 2 years |
| Change From Baseline in Mean Insulin-like Growth Factor 1 (IGF-I) Standard Deviation Score (SDS) at Specified Timepoints During Maintenance Period | Changes in the IGF-I levels were assessed as Standard Deviation Scores (SDS). The SDS 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 standard deviation (SD) vary depending on the age and sex of the participant. Change in IGF-I level (SDS) at specified timepoints from baseline was assessed. A higher score reflects a better outcome. | Baseline, Month 2 Day 1, Month 2 Day 8, Month 3 Day 1, Month 3 Day 8, Month 4 Day 1, Month 4 Day 8, Month 5 Day 1, Month 5 Day 8, Month 6 Day 1, Month 6 Day 8, Month 7 Day 1, Month 7 Day 8, Month 8 Day 1, Month 8 Day 8, Month 10 Day 1, and Month 10 Day 8 |
| Mean Insulin-like Growth Factor-binding Protein 3 (IGFBP-3) SDS During Maintenance Period | Baseline up to Month 12 |
| Received at Least 1 Dose of Study Drug |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Safety population included all participants who received any amount of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Somavaratan | Participants received once-monthly SC somavaratan per Protocol Version 1.0. The dosing regimen was then modified in Protocol Version 2.0 to twice-monthly SC somavaratan. Doses were titrated to each participant's individual IGF-I responses based on the IGF-I level 7 days postdose until a maintenance dose was achieved. Maintenance dose was defined as an IGF-I value between 0 and 2.0 SDS for two consecutive 7-day postdose time points (Day 8, peak level). Participants who received somavaratan once-monthly in this study or in a previous somavaratan study (15VR7), had their dose decreased by half (minimum dose of 20 mg, 40 mg for women on estrogen, rounded down to the nearest even number) and were titrated based on IGF-I level at Day 8. New participants enrolling in this study received a starting dose of 20 mg twice-monthly (40 mg for women on estrogen) and were titrated based on IGF-I level at Day 8. Maintenance doses were adjusted further based on PD data at the discretion of the Investigator or Medical Monitor. The maximum allowable dose of somavaratan was 250.0 mg. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| 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 | 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 | From first dose of study drug up to approximately 2 years |
|
|
| ||||||||||||||||||||||||||
| Secondary | Average Dose Level During Titration/Maintenance | Total average dose received by a participant during titration/maintenance has been reported. | Safety population included all participants who received any amount of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | mg | Up to Month 12 |
| |||||||||||||||||||||||||||
| Secondary | Number of Participants With Dose Adjustments | The number of participants with a dose adjustment (titrated up/down) at each month are summarized. | Safety population included all participants who received any amount of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants analyzed at specified timepoint. | Posted | Count of Participants | Participants | Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Were Anti-drug Antibody (ADA) Positive | Safety population included all participants who received any amount of study drug. | Posted | Count of Participants | Participants | Up to approximately 2 years |
|
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With Positive Neutralizing Antibodies (NABs) | Safety population included all participants who received any amount of study drug. | Posted | Count of Participants | Participants | Up to approximately 2 years |
|
| ||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Mean Insulin-like Growth Factor 1 (IGF-I) Standard Deviation Score (SDS) at Specified Timepoints During Maintenance Period | Changes in the IGF-I levels were assessed as Standard Deviation Scores (SDS). The SDS 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 standard deviation (SD) vary depending on the age and sex of the participant. Change in IGF-I level (SDS) at specified timepoints from baseline was assessed. A higher score reflects a better outcome. | Safety population included all participants who received any amount of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants analyzed at specified timepoint. | Posted | Mean | Standard Deviation | SDS | Baseline, Month 2 Day 1, Month 2 Day 8, Month 3 Day 1, Month 3 Day 8, Month 4 Day 1, Month 4 Day 8, Month 5 Day 1, Month 5 Day 8, Month 6 Day 1, Month 6 Day 8, Month 7 Day 1, Month 7 Day 8, Month 8 Day 1, Month 8 Day 8, Month 10 Day 1, and Month 10 Day 8 |
| |||||||||||||||||||||||||||
| Secondary | Mean Insulin-like Growth Factor-binding Protein 3 (IGFBP-3) SDS During Maintenance Period | Due to early termination of study, no data were collected for this outcome measure. | Posted | Baseline up to Month 12 |
|
|
From first dose of study drug up to approximately 2 years
Safety population included all participants who received any amount of study drug.
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 | Somavaratan | Participants received once-monthly SC somavaratan per Protocol Version 1.0. The dosing regimen was then modified in Protocol Version 2.0 to twice-monthly SC somavaratan. Doses were titrated to each participant's individual IGF-I responses based on the IGF-I level 7 days postdose until a maintenance dose was achieved. Maintenance dose was defined as an IGF-I value between 0 and 2.0 SDS for two consecutive 7-day postdose time points (Day 8, peak level). Participants who received somavaratan once-monthly in this study or in a previous somavaratan study (15VR7), had their dose decreased by half (minimum dose of 20 mg, 40 mg for women on estrogen, rounded down to the nearest even number) and were titrated based on IGF-I level at Day 8. New participants enrolling in this study received a starting dose of 20 mg twice-monthly (40 mg for women on estrogen) and were titrated based on IGF-I level at Day 8. Maintenance doses were adjusted further based on PD data at the discretion of the Investigator or Medical Monitor. The maximum allowable dose of somavaratan was 250.0 mg. | 0 | 36 | 5 | 36 | 30 | 36 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adrenal insufficiency | Endocrine disorders | 18.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | 18.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | 18.0 | Systematic Assessment |
| |
| Polydipsia | Metabolism and nutrition disorders | 18.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
| |
| Benign breast neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 18.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | 18.0 | Systematic Assessment |
| |
| Hernia | General disorders | 18.0 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | 18.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | 18.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | 18.0 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | 18.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | 18.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Very low density lipoprotein increased | Investigations | 18.0 | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | 18.0 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | 18.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
| |
| Tooth fracture | Injury, poisoning and procedural complications | 18.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Blood phosphorus decreased | Investigations | 18.0 | Systematic Assessment |
| |
| Blood phosphorus increased | Investigations | 18.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | 18.0 | Systematic Assessment |
| |
| Viral pharyngitis | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | 18.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | 18.0 | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | 18.0 | Systematic Assessment |
| |
| Low density lipoprotein increased | Investigations | 18.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | 18.0 | Systematic Assessment |
| |
| Haemangioma removal | Surgical and medical procedures | 18.0 | Systematic Assessment |
| |
| Injection site erythema | General disorders | 18.0 | Systematic Assessment |
| |
| Fatigue | General disorders | 18.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
| |
| Macule | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
| |
| Pain | General disorders | 18.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 18.0 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | 18.0 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | 18.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | 18.0 | Systematic Assessment |
| |
| White blood cell count increased | Investigations | 18.0 | Systematic Assessment |
| |
| Abdominal wall mass | Gastrointestinal disorders | 18.0 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | 18.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | 18.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | 18.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | 18.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
| |
| Injection site reaction | General disorders | 18.0 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | 18.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | 18.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Vulvovaginal mycotic infection | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | 18.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
| |
| Abdominal tenderness | Gastrointestinal disorders | 18.0 | Systematic Assessment |
| |
| Tooth extraction | Surgical and medical procedures | 18.0 | Systematic Assessment |
| |
| Joint stiffness | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | 18.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | 18.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | 18.0 | Systematic Assessment |
| |
| Skin lesion excision | Surgical and medical procedures | 18.0 | Systematic Assessment |
| |
| Middle ear inflammation | Ear and labyrinth disorders | 18.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | 18.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | 18.0 | Systematic Assessment |
| |
| Choroidal detachment | Eye disorders | 18.0 | Systematic Assessment |
| |
| Stress | Psychiatric disorders | 18.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | 18.0 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | 18.0 | Systematic Assessment |
| |
| Weight increased | Investigations | 18.0 | 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Operating Officer | Aravive, Inc. | (936) 355-1910 | clinicaltrials@aravive.com |
| Feb 2, 2023 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D004393 | Dwarfism, Pituitary |
| ID | Term |
|---|---|
| D004392 | Dwarfism |
| D001848 | Bone Diseases, Developmental |
| 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 |
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Units |
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| Participants |
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