Growth Hormone Deficiency Clinical Trial
Official title:
A Blinded Placebo Controlled Single Ascending Dose Phase 1 for Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Subcutaneous Administration of VRS-317 in Adults With Growth Hormone Deficiency
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
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 After screening patients are withdrawn from daily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
;
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
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