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 H. Hamrahian, Beverly M K Biller, Mark Kipnes, Jerome A. Moore, Eric Humphriss, George M. Bright, Jeffrey L. Cleland

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 2013

Fingerprint

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

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

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 H.; 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, 06.2013, p. 2595-2603.

Research output: Contribution to journalArticle

Yuen, KCJ, Conway, GS, Popovic, V, Merriam, GR, Bailey, T, Hamrahian, AH, Biller, BMK, Kipnes, M, Moore, JA, Humphriss, E, Bright, GM & Cleland, JL 2013, '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', Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 6, pp. 2595-2603. https://doi.org/10.1210/jc.2013-1437
Yuen, Kevin C J ; Conway, Gerard S. ; Popovic, Vera ; Merriam, George R. ; Bailey, Timothy ; Hamrahian, Amir H. ; 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.
@article{b9adfe93eb4a4510812f45340af4b493,
title = "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",
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.",
author = "Yuen, {Kevin C J} and Conway, {Gerard S.} and Vera Popovic and Merriam, {George R.} and Timothy Bailey and Hamrahian, {Amir H.} and Biller, {Beverly M K} and Mark Kipnes and Moore, {Jerome A.} and Eric Humphriss and Bright, {George M.} and Cleland, {Jeffrey L.}",
year = "2013",
month = "6",
doi = "10.1210/jc.2013-1437",
language = "English (US)",
volume = "98",
pages = "2595--2603",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

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

AU - Yuen, Kevin C J

AU - Conway, Gerard S.

AU - Popovic, Vera

AU - Merriam, George R.

AU - Bailey, Timothy

AU - Hamrahian, Amir H.

AU - Biller, Beverly M K

AU - Kipnes, Mark

AU - Moore, Jerome A.

AU - Humphriss, Eric

AU - Bright, George M.

AU - Cleland, Jeffrey L.

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878499352&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878499352&partnerID=8YFLogxK

U2 - 10.1210/jc.2013-1437

DO - 10.1210/jc.2013-1437

M3 - Article

C2 - 23585663

AN - SCOPUS:84878499352

VL - 98

SP - 2595

EP - 2603

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 6

ER -