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Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study.
Growth Horm IGF Res. 2017 10; 36:44-51.GH

Abstract

OBJECTIVE

To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (<28weeks' gestational age), based on initial sections of a phase II randomized controlled trial.

DESIGN

The phase II trial was designed in four sections (A-D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C. Infants in these study sections received rhIGF-1/rhIGFBP-3 or standard neonatal care up to postmenstrual age (weeks+days) 28+6 (Section B) or 29+6 (Section C). Dosing was variable/individualized and intended to establish serum IGF-1 within physiological intrauterine levels.

RESULTS

Nineteen infants were enrolled across Sections B/C: nine received rhIGF-1/rhIGFBP-3 and 10 standard neonatal care. Among the nine infants treated with study drug, mean (SD) dose was 95.1 (10.6)μg/kg/day and mean (SD) duration of infusion was 14.2 (6.1)days. Eight of nine (88.9%) treated infants had two or more dose changes during treatment. Mean serum IGF-1 levels during treatment were 23μg/L among treated infants compared with 14μg/L in control infants. Overall, 66.3% of IGF-1 measurements for treated infants were within target levels (20-60μg/L) versus 17.3% for control infants. Overall incidence of adverse events (AEs) was similar for treated versus control infants; AEs were generally as expected in this population, and no AEs were considered related to study treatment. There was no observed increase in infection rates (considered a possible risk with continuous intravenous infusion) between treated and control infants. Rates of hypoglycemia (considered a possible risk with IGF-1 treatment) were also similar between groups. There was one fatal serious AE of cardiac tamponade in the treated group (not considered treatment related).

CONCLUSION

Infusion of rhIGF-1/rhIGFBP-3 increased serum concentrations of IGF-1 and attainment of target levels relative to standard neonatal care. rhIGF-1/rhIGFBP-3 infusion was well tolerated with no safety signals. Although further work is required to optimize the dose regimen for attainment of physiological intrauterine levels, we believe the results reported support the feasibility of rhIGF-1/rhIGFBP-3 continuous longitudinal infusion in extremely preterm infants. The trial is registered at ClinicalTrials.gov (NCT01096784).

Authors+Show Affiliations

Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Pediatrics, Lasarettsgatan 40, SE-221 85 Lund, Sweden. Electronic address: ingrid.pupp@med.lu.se.Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11-13, 40530 Gothenburg, Sweden. Electronic address: ann.hellstrom@medfak.gu.se.Shire, 300 Shire Way, Lexington, MA 02421, USA. Electronic address: mhamdani@shire.com.Shire, Zählerweg 10, 6300 Zug, Switzerland. Electronic address: atocoian@shire.com.Shire, 300 Shire Way, Lexington, MA 02421, USA.Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Pediatrics, Lasarettsgatan 40, SE-221 85 Lund, Sweden. Electronic address: david.ley@med.lu.se.Department of Neonatology, CLINTEC, Karolinska Institutet and Karolinska University Hospital, Karolinska vägen 8, 171 76 Stockholm, Sweden. Electronic address: Boubou.Hallberg@ki.se.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28934640

Citation

Hansen-Pupp, Ingrid, et al. "Continuous Longitudinal Infusion of rhIGF-1/rhIGFBP-3 in Extremely Preterm Infants: Evaluation of Feasibility in a Phase II Study." Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society, vol. 36, 2017, pp. 44-51.
Hansen-Pupp I, Hellström A, Hamdani M, et al. Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study. Growth Horm IGF Res. 2017;36:44-51.
Hansen-Pupp, I., Hellström, A., Hamdani, M., Tocoian, A., Kreher, N. C., Ley, D., & Hallberg, B. (2017). Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study. Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society, 36, 44-51. https://doi.org/10.1016/j.ghir.2017.08.004
Hansen-Pupp I, et al. Continuous Longitudinal Infusion of rhIGF-1/rhIGFBP-3 in Extremely Preterm Infants: Evaluation of Feasibility in a Phase II Study. Growth Horm IGF Res. 2017;36:44-51. PubMed PMID: 28934640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study. AU - Hansen-Pupp,Ingrid, AU - Hellström,Ann, AU - Hamdani,Mohamed, AU - Tocoian,Adina, AU - Kreher,Nerissa C, AU - Ley,David, AU - Hallberg,Boubou, Y1 - 2017/08/31/ PY - 2017/03/10/received PY - 2017/07/14/revised PY - 2017/08/29/accepted PY - 2017/9/22/pubmed PY - 2018/6/28/medline PY - 2017/9/22/entrez KW - Complications of prematurity KW - Continuous infusion KW - IGF-1 KW - Preterm infants KW - Randomized controlled trial KW - Retinopathy of prematurity KW - rhIGF-1/rhIGFBP-3 SP - 44 EP - 51 JF - Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society JO - Growth Horm IGF Res VL - 36 N2 - OBJECTIVE: To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (<28weeks' gestational age), based on initial sections of a phase II randomized controlled trial. DESIGN: The phase II trial was designed in four sections (A-D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C. Infants in these study sections received rhIGF-1/rhIGFBP-3 or standard neonatal care up to postmenstrual age (weeks+days) 28+6 (Section B) or 29+6 (Section C). Dosing was variable/individualized and intended to establish serum IGF-1 within physiological intrauterine levels. RESULTS: Nineteen infants were enrolled across Sections B/C: nine received rhIGF-1/rhIGFBP-3 and 10 standard neonatal care. Among the nine infants treated with study drug, mean (SD) dose was 95.1 (10.6)μg/kg/day and mean (SD) duration of infusion was 14.2 (6.1)days. Eight of nine (88.9%) treated infants had two or more dose changes during treatment. Mean serum IGF-1 levels during treatment were 23μg/L among treated infants compared with 14μg/L in control infants. Overall, 66.3% of IGF-1 measurements for treated infants were within target levels (20-60μg/L) versus 17.3% for control infants. Overall incidence of adverse events (AEs) was similar for treated versus control infants; AEs were generally as expected in this population, and no AEs were considered related to study treatment. There was no observed increase in infection rates (considered a possible risk with continuous intravenous infusion) between treated and control infants. Rates of hypoglycemia (considered a possible risk with IGF-1 treatment) were also similar between groups. There was one fatal serious AE of cardiac tamponade in the treated group (not considered treatment related). CONCLUSION: Infusion of rhIGF-1/rhIGFBP-3 increased serum concentrations of IGF-1 and attainment of target levels relative to standard neonatal care. rhIGF-1/rhIGFBP-3 infusion was well tolerated with no safety signals. Although further work is required to optimize the dose regimen for attainment of physiological intrauterine levels, we believe the results reported support the feasibility of rhIGF-1/rhIGFBP-3 continuous longitudinal infusion in extremely preterm infants. The trial is registered at ClinicalTrials.gov (NCT01096784). SN - 1532-2238 UR - https://www.unboundmedicine.com/medline/citation/28934640/Continuous_longitudinal_infusion_of_rhIGF_1/rhIGFBP_3_in_extremely_preterm_infants:_Evaluation_of_feasibility_in_a_phase_II_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-6374(17)30074-6 DB - PRIME DP - Unbound Medicine ER -