A long-acting human growth hormone with delayed clearance (VRS-317): Results of a double-blind, placebo-controlled, single ascending dose study in growth hormone-deficient adults

Kevin C.J. Yuen, Gerard S. Conway, Vera Popovic, George R. Merriam, Timothy Bailey, Amir Hamrahian, Beverly M.K. Biller, Mark Kipnes, Jerome A. Moore, Eric Humphriss, George M. Bright, Jeffrey L. Cleland

Research output: Contribution to journalArticle

Abstract

Background: Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes. Objectives: This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317. Design: This was a randomized, double-blind, placebo-controlled, single ascending dose study. Patients: Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo). Setting: The study was conducted in 17 adult endocrinology centers in North America and Europe. Main Outcome Measures: Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed. Results: At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3-5.0 μg/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between -1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed. Conclusions: The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing.

Original languageEnglish (US)
Pages (from-to)2595-2603
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

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Human Growth Hormone
Insulin-Like Growth Factor I
Growth Hormone
Placebos
Pharmacodynamics
Pharmacokinetics
Safety
Half-Life
Endocrinology
Insulin-Like Growth Factor Binding Protein 3
Patient Compliance
North America
Reference Values
Outcome Assessment (Health Care)
Therapeutics
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

A long-acting human growth hormone with delayed clearance (VRS-317) : Results of a double-blind, placebo-controlled, single ascending dose study in growth hormone-deficient adults. / Yuen, Kevin C.J.; Conway, Gerard S.; Popovic, Vera; Merriam, George R.; Bailey, Timothy; Hamrahian, Amir; Biller, Beverly M.K.; Kipnes, Mark; Moore, Jerome A.; Humphriss, Eric; Bright, George M.; Cleland, Jeffrey L.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 6, 01.06.2013, p. 2595-2603.

Research output: Contribution to journalArticle

Yuen, Kevin C.J. ; Conway, Gerard S. ; Popovic, Vera ; Merriam, George R. ; Bailey, Timothy ; Hamrahian, Amir ; Biller, Beverly M.K. ; Kipnes, Mark ; Moore, Jerome A. ; Humphriss, Eric ; Bright, George M. ; Cleland, Jeffrey L. / A long-acting human growth hormone with delayed clearance (VRS-317) : Results of a double-blind, placebo-controlled, single ascending dose study in growth hormone-deficient adults. In: Journal of Clinical Endocrinology and Metabolism. 2013 ; Vol. 98, No. 6. pp. 2595-2603.
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abstract = "Background: Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes. Objectives: This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317. Design: This was a randomized, double-blind, placebo-controlled, single ascending dose study. Patients: Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo). Setting: The study was conducted in 17 adult endocrinology centers in North America and Europe. Main Outcome Measures: Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed. Results: At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3-5.0 μg/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between -1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed. Conclusions: The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing.",
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T1 - A long-acting human growth hormone with delayed clearance (VRS-317)

T2 - Results of a double-blind, placebo-controlled, single ascending dose study in growth hormone-deficient adults

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AU - Conway, Gerard S.

AU - Popovic, Vera

AU - Merriam, George R.

AU - Bailey, Timothy

AU - Hamrahian, Amir

AU - Biller, Beverly M.K.

AU - Kipnes, Mark

AU - Moore, Jerome A.

AU - Humphriss, Eric

AU - Bright, George M.

AU - Cleland, Jeffrey L.

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