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12-Month effects of once-weekly sustained-release growth hormone treatment in adults with GH deficiency

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Abstract

The weekly sustained-release recombinant human GH formulation LB03002, showed beneficial effects in GH-deficient (GHD) adults in a previous 26-week double-blind study. Prior studies of long-acting GH preparations in adults have only been conducted for 6 or 8 months, so the effects of longer-term use are unknown; this is important to address, as replacement is given for many years in GHD adults. This open-label, 26-week study extension evaluated longer-term safety and efficacy of LB03002 over 52 weeks in adults with GHD who had previously been randomized to GH, and provides additional safety and efficacy data over 26 weeks in the cohort who had previously been randomized to placebo. Of 147 adults with GHD who completed a preceding study, 136 patients continued in this open-label study to receive LB03002 over an additional 26 weeks. This represented a continuation of long-acting GH for 26 weeks in the cohort who took this medication in the prior study (LB03002 Throughout group), and describes the first use of long-acting GH in the cohort that was randomized to placebo in the prior study (Switched to LB03002 group). The LB03002 dose was adjusted according to serum insulin-like growth factor-I (IGF-I) levels. LB03002 treatment demonstrated mean significant decreases from baseline in fat mass (FM) for both 26 (Switched group, P = 0.001) and 52 weeks (Throughout group, P = 0.002) of 1.11 (1.95) kg and 1.06 (3.16) kg, respectively. Prolonged GH treatment was effective in sustaining the increase in lean body mass (LBM), serum IGF-I and IGFBP-3 levels achieved during the first 26 weeks. Long-term treatment with the sustained-release weekly GH preparation over both 26 and 52 weeks in adults with GHD demonstrated a sustained reduction of FM with a favorable safety profile. This study extends prior knowledge about long-acting GH because it reports the most prolonged treatment of adults with any long-acting GH preparation, thereby confirming the value and safety of such agents for long-term GH replacement.

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Acknowledgments

Jointly by LG Life Sciences, Ltd., Korea, and Biopartners GmbH, Switzerland. We thank the late Mircea Popa, Medical Center Sana, Bucharest, Romania, who significantly contributed to the study. His associate Catalin Gavrila continued his work in this study and co-authors this manuscript. We acknowledge the significant contributions by Jin Hwa Lee, Songmi Lee, Leah Suh, Karin Sulzer, and John Kim.

In addition to the authors, this clinical trial was conducted by the following investigators: Anton Luger, M.D. (University of Vienna, Vienna, Austria); Josef Marek, M.D. (Vseobecna Fakultni Nemocnice, Praha, Czech Republic); Jan Cap, M.D. (Fakultni Nemocnice Hradec Kralove, Hradec Kralove, Czech Republic); Zdnek Frysak, M.D. (Fakultni Nemocnice Olomouc, Olomouc, Czech Republic); Philippe Chanson, M.D. (Centre Hospitalier Universitaire de Bicêtre, Paris, France); Francoise Borson-Chazot, M.D. (Hôpital Neurocardiologique Fédération d’Endocrinologie, Lyon, France); Georges Weryha, M.D. (Centre Hospitalier Universitaire de Nancy, Nancy, France); Michael Faust, M.D. (Klinikum der Universität zu Köln, Cologne, Germany); Roland Pfäffle, M.D. (Universitätsklinikum Leipzig, Leipzig, Germany); Jochen Schopohl, M.D. (Universitätsklinikum München, München, Germany); Harald Lahner, M.D. (Essen, Germany); Slawomir Mucha, M.D. (Independent Public Clinical Hospital, Sterlinga, Poland); Eusebie Zbranca, M.D. (Clinica de Endocrinologie, Iasi, Romania); Ioana Zosin, M.D. (Spitalul Clinic Judetean de Urgenta, Timisoara, Romania); Jan Podoba, M.D. (Interna Klinika FNsP, Bratislava, Slovakia); Felipe Casanueva, M.D. (Hospital Médico-Quirúrgico de Conxo, Santiago, Spain); Susan Webb, M.D. (Hospital de la Santa Creu i Sant Pau, Barcelona, Spain); Manel Puig, M.D. (Hospital Clinic I Provincial, Barcelona, Spain); Gudmundur Johannsson, M.D. (Universitetssjukhuset Göteborg, Göteborg, Sweden); Charlotte Höybye, M.D. (Karolinska Universitetssjukhuset Solna, Stockholm, Sweden); Richard Ross, M.D. (Royal Hallamshire Hospital, Sheffield, UK); Laurence Katznelson, M.D. (Stanford University Medical Center, Stanford, CA); David Kleinberg, M.D. (New York University School of Medicine, New York, NY) and Amir Hamrahian, M.D. (Cleveleand, OH).

Conflict of interest

H.J.J. and H.A. are employees of LG Life Sciences, Ltd.; C.S. and E.C.S. are employees of Biopartners, GmbH.; B.M.K.B. and C.J.S. received consulting fees from LG Life Sciences, Ltd., Korea, and Biopartners, GmbH, Switzerland.; V.P., M.C., J.R., C.G., and D.M.C. have nothing to declare.

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Authors and Affiliations

  1. Massachusetts General Hospital, Boston, MA, 02114, USA

    Beverly M. K. Biller

  2. LG Life Sciences Ltd, Seoul, 110-062, Korea

    Hyi-Jeong Ji & Hyunji Ahn

  3. Biopartners GmbH, 6340, Baar, Switzerland

    Conrad Savoy & E. Christine Siepl

  4. University of Belgrade, 11000, Belgrade, Serbia

    Vera Popovic

  5. National Institute of Endocrinology “C.I.Parhon”, 011863, Bucharest, Romania

    Mihail Coculescu

  6. SANA Medical Center, 011025, Bucharest, Romania

    Catalin Gavrila

  7. University of Munich, 80336, Munchen, Germany

    Josefine Roemmler

  8. Oregon Health and Science University, Portland, OR, 97239, USA

    David M. Cook

  9. Charité—Universitätsmedizin Campus Mitte, 10117, Berlin, Germany

    Christian J. Strasburger

Authors
  1. Beverly M. K. Biller
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  2. Hyi-Jeong Ji
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  3. Hyunji Ahn
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  4. Conrad Savoy
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  5. E. Christine Siepl
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  6. Vera Popovic
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  7. Mihail Coculescu
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  8. Josefine Roemmler
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  9. Catalin Gavrila
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  10. David M. Cook
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  11. Christian J. Strasburger
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Corresponding author

Correspondence to Hyunji Ahn.

Additional information

Clinical trial identifier: NCT00596037.

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Biller, B.M.K., Ji, HJ., Ahn, H. et al. 12-Month effects of once-weekly sustained-release growth hormone treatment in adults with GH deficiency. Pituitary 16, 311–318 (2013). https://doi.org/10.1007/s11102-012-0422-8

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  • DOI: https://doi.org/10.1007/s11102-012-0422-8

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