Versartis Long-Term Safety Study of Somavaratan (VISTA)

An Open-Label, Long-Term Safety Study of A Long-acting Human Growth Hormone Somavaratan (VRS-317) in Children With Growth Hormone Deficiency

Protocol 13VR3 is is a multi-center, open-label study assessing long-term somavaratan administration.

Patients will be monitored for safety throughout their participation in the study. Safety will be monitored by physical examination, inspection of injection sites, vital signs, clinical laboratory determinations (including fasting glucose, insulin, and lipids), 12-lead ECGs (for new treatment naïve subjects and subjects not previously exposed to somavaratan), PK/PD assessments, and immunogenicity assessments.

Adverse events (AEs) and concomitant medications will be captured. AEs will be coded using CTCAE v 4.0. AEs will be coded using the MedDRA dictionary and CMs using the WHO Drug dictionary.

Study Overview

• Status: Terminated
• Conditions: Pediatric Growth Hormone Deficiency
• Intervention / Treatment: Drug: somavaratan

Detailed Description

Protocol 13VR3 is a multi-center, open-label study assessing long-term somavaratan administration. It is open to subjects completing a somavaratan study in children with growth hormone deficiency (GHD), as well as up to 100 new treatment naïve subjects with GHD. All subjects will receive somavaratan 3.5 mg/kg twice monthly. The study will be conducted at approximately 70 Pediatric Endocrinology centers in the United States, Canada, and Europe.

• Study Type: Interventional
• Enrollment (Actual): 385
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for Subjects Completing a Previous Somavaratan Study:

1. Completion of a somavaratan clinical study.
2. Willing and able to comply with all study procedures.

Exclusion Criteria for Subjects Completing a Previous somavaratan Study:

1. Withdrawal from a somavaratan clinical study.
2. Use of certain medications with potential to alter responses to the test product.
3. Presence of a significant medical condition.

Inclusion Criteria for New Treatment Naïve Subjects:

1. Chronological Age ≥ 3.0 years.
2. Pre-pubertal status.
3. Diagnosis of GHD as documented by two or more GH stimulation test results ≤ 10.0 ng/mL.
4. Normal thyroid function at Screening Visit in subjects not being treated for hypothyroidism.
5. Normal adrenal function at Screening Visit or within 6 months of the Screening Visit, in subjects not being treated for adrenal insufficiency. Subjects with adrenal insufficiency must receive glucocorticoid treatment for a minimum of 4 weeks before study drug administration.
6. Pathology relating to cause of GHD must be stable for at least 6 months prior to screening.
7. Legally authorized representatives must be willing and able to give informed consent.

Exclusion Criteria for New Treatment Naïve Subjects:

1. Prior/concomitant treatment with any growth promoting agent.
2. Current, significant disease.
3. Chromosomal aneuploidy, significant gene mutations or confirmed diagnosis of a named syndrome.
4. Birth weight and/or birth length less than 5th percentile for gestational age.
5. Prolonged daily use of anti-inflammatory doses of oral glucocorticoids.
6. Prior history of malignancy.
7. Treatment with an investigational drug in the 30 days prior to screening.
8. Known allergy to constituents of the study drug formulation.
9. Ocular findings suggestive of increased intracranial pressure and/or retinopathy at screening.
10. Significant spinal abnormalities including scoliosis, kyphosis, Chiari malformation, and spina bifida variants.
11. Significant abnormality in screening studies.
12. History of pancreatitis or undiagnosed chronic abdominal pain.
13. History of spinal or total body irradiation.
14. Other pituitary hormone deficiencies that are not properly treated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment naive subjects with GHD; Up to 100 new treatment naïve subjects with GHD will receive somavaratan 3.5mg/kg twice monthly.	Drug: somavaratan; Subcutaneous injection; Other Names: VRS-317
Experimental: Subjects who have completed a somavaratan study; All subjects after participation in (12VR2) or participation in the 14VR4 protocols have the option to receive somavaratan 3.5mg/kg twice monthly.	Drug: somavaratan; Subcutaneous injection; Other Names: VRS-317

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Safety assessments include recording of adverse events and concomitant medications, monitoring of injection sites, vital signs and clinical laboratory determinations.	Up to 4 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the changes in pharmacodynamics (PD) responses, bone age, weight, height velocity, height standard deviation scores, metabolic parameters, pubertal development and anti-drug antibody responses during long-term somavaratan treatment	PK/PD peak and trough measurements will be assessed throughout the study with assessment of plasma VRS-317 concentrations and IGF-I and its binding proteins measured at pre-specified time points.	Up to 4 years

Collaborators and Investigators

• Sponsor: Versartis Inc.
• Investigators: Study Director: Will Charlton, MD, Versartis Inc.

Publications and helpful links

Helpful Links

• Versartis website

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2014
• Primary Completion (Actual): November 17, 2017
• Study Completion (Actual): November 17, 2017

Study Registration Dates

• First Submitted: February 6, 2014
• First Submitted That Met QC Criteria: February 19, 2014
• First Posted (Estimate): February 21, 2014

Study Record Updates

• Last Update Posted (Actual): March 9, 2018
• Last Update Submitted That Met QC Criteria: March 7, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Growth Hormone Deficiency; Growth hormone; IGF-I; GHD; Pediatric Growth Hormone Deficiency; PGHD; VRS-317; Versartis; Height velocity; Short stature; Growth disorder; Long acting growth hormone; Weekly growth hormone dosing; Semi-monthly growth hormone dosing; Monthly growth hormone dosing; Annual height velocity; Growth rate; Somavaratan
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary; Endocrine System Diseases
• Other Study ID Numbers: 13VR3