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A first-in-human, double-blind, randomised, placebo-controlled, dose ascending study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee osteoarthritis

Dahlberg, Leif E LU ; Aydemir, Aida; Muurahainen, Norma; Gühring, Hans; Fredberg Edebo, Helena; Krarup-Jensen, Niels; Ladel, Christoph H and Jurvelin, Jukka S (2016) In Clinical and Experimental Rheumatology 34(3). p.50-445
Abstract

OBJECTIVES: To evaluate the safety of intra-articular sprifermin (primary), and to evaluate systemic exposure, biomarkers, histology, and other cartilage parameters in patients with advanced osteoarthritis (OA).

METHODS: This was a first-in-human, double-blind, randomised, placebo-controlled trial of single and multiple ascending doses of sprifermin from 3-300 μg in knee OA patients scheduled for total knee replacement. Patients were randomised 3:1 to sprifermin or placebo, injected into the target knee once or once weekly for 3 weeks, and followed-up for 24 weeks.

RESULTS: Fifty-five patients were treated with sprifermin, 25 with single and 30 with multiple doses, 18 received placebo. There was no clear difference between... (More)

OBJECTIVES: To evaluate the safety of intra-articular sprifermin (primary), and to evaluate systemic exposure, biomarkers, histology, and other cartilage parameters in patients with advanced osteoarthritis (OA).

METHODS: This was a first-in-human, double-blind, randomised, placebo-controlled trial of single and multiple ascending doses of sprifermin from 3-300 μg in knee OA patients scheduled for total knee replacement. Patients were randomised 3:1 to sprifermin or placebo, injected into the target knee once or once weekly for 3 weeks, and followed-up for 24 weeks.

RESULTS: Fifty-five patients were treated with sprifermin, 25 with single and 30 with multiple doses, 18 received placebo. There was no clear difference between the active and placebo groups in incidence, severity, and nature of reported treatment emergent adverse events. Acute inflammatory reactions were slightly more common with sprifermin 300 μg, but none led to discontinuation. No clear difference was seen between placebo and sprifermin in physician-assessed local tolerability, pain, or swelling in the knee. No meaningful changes over time, or differences between treatment groups, were observed for safety laboratory parameters or ECG. Although individual abnormalities were observed, no patterns were evident suggesting a relation to treatment or potential safety concern. No systemic sprifermin exposure, anti-FGF18 antibodies, or clear-cut effects on systemic biomarkers were detected.

CONCLUSIONS: This first clinical trial of sprifermin revealed no serious safety concerns, although larger studies are needed. The possibility of positive effects of intra-articular sprifermin on histological and other cartilage parameters in knee OA also warrant further investigation.

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author
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type
Contribution to journal
publication status
published
subject
in
Clinical and Experimental Rheumatology
volume
34
issue
3
pages
50 - 445
publisher
Pacini
external identifiers
  • Scopus:84982850713
ISSN
0392-856X
language
English
LU publication?
yes
id
61a8d5d4-ee68-4a5c-ac07-709743fe6257
date added to LUP
2016-04-28 13:06:24
date last changed
2017-01-01 08:24:04
@article{61a8d5d4-ee68-4a5c-ac07-709743fe6257,
  abstract     = {<p>OBJECTIVES: To evaluate the safety of intra-articular sprifermin (primary), and to evaluate systemic exposure, biomarkers, histology, and other cartilage parameters in patients with advanced osteoarthritis (OA).</p><p>METHODS: This was a first-in-human, double-blind, randomised, placebo-controlled trial of single and multiple ascending doses of sprifermin from 3-300 μg in knee OA patients scheduled for total knee replacement. Patients were randomised 3:1 to sprifermin or placebo, injected into the target knee once or once weekly for 3 weeks, and followed-up for 24 weeks.</p><p>RESULTS: Fifty-five patients were treated with sprifermin, 25 with single and 30 with multiple doses, 18 received placebo. There was no clear difference between the active and placebo groups in incidence, severity, and nature of reported treatment emergent adverse events. Acute inflammatory reactions were slightly more common with sprifermin 300 μg, but none led to discontinuation. No clear difference was seen between placebo and sprifermin in physician-assessed local tolerability, pain, or swelling in the knee. No meaningful changes over time, or differences between treatment groups, were observed for safety laboratory parameters or ECG. Although individual abnormalities were observed, no patterns were evident suggesting a relation to treatment or potential safety concern. No systemic sprifermin exposure, anti-FGF18 antibodies, or clear-cut effects on systemic biomarkers were detected.</p><p>CONCLUSIONS: This first clinical trial of sprifermin revealed no serious safety concerns, although larger studies are needed. The possibility of positive effects of intra-articular sprifermin on histological and other cartilage parameters in knee OA also warrant further investigation.</p>},
  author       = {Dahlberg, Leif E and Aydemir, Aida and Muurahainen, Norma and Gühring, Hans and Fredberg Edebo, Helena and Krarup-Jensen, Niels and Ladel, Christoph H and Jurvelin, Jukka S},
  issn         = {0392-856X},
  language     = {eng},
  month        = {05},
  number       = {3},
  pages        = {50--445},
  publisher    = {Pacini},
  series       = {Clinical and Experimental Rheumatology},
  title        = {A first-in-human, double-blind, randomised, placebo-controlled, dose ascending study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee osteoarthritis},
  volume       = {34},
  year         = {2016},
}