Versartis Trial in Children to Assess Long-Acting Growth Hormone (VERTICAL)

A Long-acting Human Growth Hormone (VRS-317) in Pre-pubertal Children With Growth Hormone Deficiency: A Randomized, Open-label, Multi-center, Phase 1b/2a Study of Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and Efficacy After Subcutaneous Administration for 6 Months

This is a Phase 1b/2a study of VRS-317 (long-acting growth hormone) in pediatric patients with growth hormone deficiency. During Phase 1b, pediatric patients each will receive a single subcutaneous injection of VRS-317. During the Phase 2a stage, patients will receive 6 months of VRS-317 treatment at dose levels selected from the Phase 1b stage. The primary endpoints for the study are to determine the safety and efficacy of repeat dose VRS-317.

Study Overview

• Status: Completed
• Conditions: Pediatric Growth Hormone Deficiency
• Intervention / Treatment: Drug: Experimental: VRS-317

Detailed Description

In Phase 1b, separate cohorts of patients will be tested in a single ascending dose format. Safety review committee meetings will take place prior to escalating to each increasing dose level. Enrolled patients will be monitored for 60 days for safety with PK/PD and safety labs collected.

Two dose levels will be selected after completion of Phase 1b to be tested during Phase 2a (6 months of continuous VRS-317 treatment). Safety and PK assessments will be made during the Phase 2a stage. Patient heights will be measured by stadiometer.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Clovis, California, United States
    • Los Angeles, California, United States
    • San Diego, California, United States
    • San Francisco, California, United States
  • Colorado
    • Greenwood Village, Colorado, United States
  • Florida
    • Orlando, Florida, United States
    • Tallahassee, Florida, United States
    • Tampa, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Massachusetts
    • Springfield, Massachusetts, United States
  • Minnesota
    • Minneapolis, Minnesota, United States
  • Missouri
    • Kansas City, Missouri, United States
  • New Jersey
    • Livingston, New Jersey, United States
    • Morristown, New Jersey, United States
  • New York
    • Buffalo, New York, United States
    • Mineola, New York, United States
    • Sleepy Hollow, New York, United States
  • Ohio
    • Cleveland, Ohio, United States
    • Columbus, Ohio, United States
  • Texas
    • San Antonio, Texas, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronological Age ≥ 3.0 years and ≤ 11.0
• Diagnosis of GHD as documented by GH stimulation test
• Below average height SDS at screening
• Appropriate weight for Stature
• Decreased IGF-I SDS at screening
• Delayed bone age
• Normal thyroid function test results at screening visit
• Legally authorized representative informed consent.

Exclusion Criteria:

• Prior treatment with any growth promoting agent
• Documented history of, or current, significant disease
• Chromosomal aneuploidy, significant gene mutations
• Diagnosis of Attention Deficit Hyperactivity Disorder
• Daily use of anti-inflammatory doses of glucocorticoid
• Prior history of leukemia, lymphoma, sarcoma or cancer
• Known allergy to constituents of the study drug formulation
• Abnormal ocular findings at screening
• Significant abnormality in screening laboratory studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VRS-317; Active treatment arm	Drug: Experimental: VRS-317; Active treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b and 2a: Evaluate the safety and tolerability of multiple dosing levels of subcutaneous (SC) VRS-317 in pediatric growth hormone deficient (GHD) patients. Phase 2a: Evaluate the efficacy of multiple dose levels of VRS-317	Safety observations will include the number of patients with adverse events, concomitant medications, safety labs, vital signs, physical exams, single dose immunogenicity (Phase 1b), and repeat dose immunogenicity (Phase 2a). The primary efficacy outcome measure is the height velocity over 6 months as measured by standing height taken with stadiometer at baseline and after 6 Months of VRS-317 dosing in Phase 2a.	8 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate pharmacokinetic measures of VRS-317.	Secondary outcome measures include evaluation of pharmacokinetics (PK) of VRS-317 including Cmax, Tmax and AUC. PK measures will be analysed at multiple timepoints after single dosing of VRS-317 during Phase 1b and after repeat dosing of VRS-317 during Phase 2a.	8 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate secondary efficacy measures after 6 months of VRS-317 dosing.	Secondary efficacy measures during Phase 2a include change in height SDS and change in bone age after 6 months VRS-317 treatment.	6 Months
Evaluate pharmacodynamic measures	Secondary outcome measures include evaluation of pharmacodynamics (PD) as measured by IGF-I and IGFBP-3 responses to single dose VRS-317 during Phase 1b and as measured by IGF-I and IGFBP-3 responses to multiple doses of VRS-317 after repeat dosing during Phase 2a. PD measures will be obtained at multiple timepoints during Phase 1b and Phase 2a.	8 Months

Collaborators and Investigators

• Sponsor: Versartis Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: October 19, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (Estimate): October 31, 2012

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 22, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Growth; Growth hormone deficiency; Growth hormone; GHD; PGHD; Versartis; Long acting growth hormone; Pediatric growth hormone deficiency; VRS 317; Exten
• 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: VRS-317 Protocol 12VR2