VRS-317 in Adult Subjects With Growth Hormone Deficiency
Condition: Growth Hormone Deficiency
MeSH terms: Dwarfism, Pituitary; Endocrine System Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this research study is to determine the safety and tolerability of up to five
      doses of VRS-317 in Adult Growth Hormone Deficient patients.

        -  Patients will be evaluated for evidence of activity of VRS-317 by measurement of changes
           from baseline in insulin-like growth factor-1 (IGF-I) and binding protein (IGFBP-3), and
           bone turnover (bone alkaline phosphatase)

        -  Descriptive pharmacokinetic (PK) and pharmacodynamic (PD) parameters (IGF-I and IGFBP-3)
           will be determined by standard model independent methods based on the plasma
           concentration-time data of each subject. These parameters include: Cmax, Tmax, AUCavg,
           AUC0-inf, and t1/2.

        -  The purpose is to determine the appropriate dose of VRS-317 to maintain a normal range
           (for appropriate age/gender) for IGF-I levels in adult patients for up to one month
           after administration of a single dose
    

Detailed description: 
      The study is a placebo controlled single ascending dose (SAD) study in adult GHD patients
      currently receiving daily rhGH therapy. After screening patients are withdrawn from daily
      rhGH therapy for a minimum of 7 days (maximum of 60 days) prior to randomization for
      treatment. Patients will be randomised within a treatment group that is currently being
      enrolled once the patient has passed the pre-dose screening criteria.

      Documented confirmation (medical history) of GHD during adulthood by a minimum of one or more
      GH stimulation tests is required such as:

        -  insulin tolerance test (ITT; peak hGH ≤ 5.0 ng/mL),

        -  arginine alone (peak hGH ≤ 0.4 ng/mL);

        -  arginine + growth-hormone-releasing hormone* (see below);

        -  or glucagon stimulation test (peak hGH ≤ 3.0 ng/mL) OR

        -  at least 3 other pituitary hormone deficiencies and a low IGF-I for age/gender
           appropriate normal range

      Each patient will be randomised to receive either the investigational product, VRS-317
      (Cohorts A-E), or placebo (Cohort F) in a 4:1 ratio.

      Subjects will be monitored for safety throughout their participation in the study. To ensure
      patient safety, two patients (1 active, 1 placebo) in the first treatment group, one from
      Cohort A and one from Cohort F1, will be dosed in a blinded manner and monitored for 48 hr
      prior to dosing the remaining 8 patients. The 8 remaining patients will be blinded and
      randomized to the first treatment group. Vital signs, clinical lab values, adverse events
      (AEs) and concomitant medications (CMs) will be captured. AEs will be graded using the Common
      Terminology Criteria for Adverse Events (CTCAE v 4.0)1, and the Primary Dermal Irritation
      Scoring Scale; AEs will be coded using the MedDRA2 dictionary and CMs using the WHO Drug
      dictionary. Prior to escalating to a higher dose level, safety data will be reviewed by the
      principal investigator (PI), co-PIs, the Sponsor, and the medical monitor for any potential
      safety risk to subjects.

      Patients will participate for a total of 83-215 days. A 7-60 day withdrawal phase (no daily
      rhGH therapy) is followed by receiving assigned doses on Day 1 of Treatment Phase, PK/PD and
      safety assessments for 30 days, and an additional 30 days of follow up.

      Safety evaulations will be performed to assess safety including but not limited to:

        -  Physical examination

        -  Vital signs (including sitting/supine blood pressure)

        -  Laboratory tests: hematology, chemistry, urinalysis, and pregnancy testing (in women of
           child-bearing age)

        -  Adverse events and concomitant medications

        -  Glucose metabolism: Fasting and post-prandial plasma glucose and fasting insulin
           pre-study and at pre-scheduled timepoints during the study (per Assessment Table)

        -  Lipid profile will be assessed pre-study and at pre-scheduled timepoints during the
           study (per Assessment Table)

        -  Assessment for adrenal insufficiency prior to enrollment and at Day 30 (not performed on
           patients with documented history of adrenal insufficiency)

        -  Evaluation of injection site reactions

        -  Anti-VRS-317 antibody assay (pre-dose, Day 30 (end of study) and Day 60) last follow up
           visit

        -  Safety monitoring will continue for up to 60 days post-dose
    

Intervention name(s): VRS-317; VRS-317; VRS-317; VRS-317; VRS-317
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): VRS-317 Single Dose; VRS-317 Single Dose; VRS-317 Single Dose; VRS-317 Single dose; VRS-317 Single dose
Other intervention name(s): Growth Hormone Deficiency; rhGH; hGH; AGHD; IGF-I; IGFBP-3; Hormones; Hormone Substitutes; Endocrine System Disease; Bone Diseases; Bone Diseases, Developmental; Musculoskeletal Diseases; Bone Disease, Endocrine; Metabolic Diseases; Hypopituitarism; Pituitary Disease; Hypothalmic Disease; Growth Hormone Replacement Therapy; Hormone Replacement Therapy; Growth Hormone Releasing Hormone; Versartis; VRS317; Growth Hormone Deficiency; rhGH; hGH; AGHD; IGF-I; IGFBP-3; Hormones; Hormone Substitutes; Endocrine System Disease; Bone Diseases; Bone Diseases, Developmental; Musculoskeletal Diseases; Bone Disease, Endocrine; Metabolic Diseases; Hypopituitarism; Pituitary Disease; Hypothalmic Disease; Growth Hormone Replacement Therapy; Hormone Replacement Therapy; Growth Hormone Releasing Hormone; Versartis; VRS317; Growth Hormone Deficiency; rhGH; hGH; AGHD; IGF-I; IGFBP-3; Hormones; Hormone Substitutes; Endocrine System Disease; Bone Diseases; Bone Diseases, Developmental; Musculoskeletal Diseases; Bone Disease, Endocrine; Metabolic Diseases; Hypopituitarism; Pituitary Disease; Hypothalmic Disease; Growth Hormone Replacement Therapy; Hormone Replacement Therapy; Growth Hormone Releasing Hormone; Versartis; VRS317; Arms:; Other Names:; Growth Hormone Deficiency; rhGH; hGH; AGHD; IGF-I; IGFBP-3; Hormones; Hormone Substitutes; Endocrine System Disease; Bone Diseases; Bone Diseases, Developmental; Musculoskeletal Diseases; Bone Disease, Endocrine; Metabolic Diseases; Hypopituitarism; Pituitary Disease; Hypothalmic Disease; Growth Hormone Replacement Therapy; Hormone Replacement Therapy; Growth Hormone Releasing Hormone; Versartis; Growth Hormone Deficiency; rhGH; hGH; AGHD; IGF-I; IGFBP-3; Hormones; Hormone Substitutes; Endocrine System Disease; Bone Diseases; Bone Diseases, Developmental; Musculoskeletal Diseases; Bone Disease, Endocrine; Metabolic Diseases; Hypopituitarism; Pituitary Disease; Hypothalmic Disease; Growth Hormone Replacement Therapy; Hormone Replacement Therapy; Growth Hormone Releasing Hormone; Versartis; VRS317
Intervention MeSH terms: Hormones; Growth Hormone-Releasing Hormone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Growth Hormone Deficiency; rhGH; hGH; Versartis; AGHD; Hormones; Hormone substitute; Endocrin System disease; Bone disease; Bone disease, developmental; Bone diseases; Musculoskeletal diseases; Bone diseases, endocrine; Metabolism diseases; Hypopituitarism; Pituitary disease; Hypothalmic disease; Brain disease; Growth Hormone Releasing Hormone; Hormone replacement therapy; IGF-I; IGFBP-3