Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study
Abstract Background Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain, leaving patients incapacitated for months to years. With no available vaccine or specific therapeutic for any alphavi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | BMC Musculoskeletal Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12891-021-04123-w |
| _version_ | 1818910696381874176 |
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| author | Ravi Krishnan Melanie Duiker Penny A. Rudd Donna Skerrett James G. D. Pollard Carolyn Siddel Rifat Rifat Jennifer H. K. Ng Peter Georgius Lara J. Hererro Paul Griffin |
| author_facet | Ravi Krishnan Melanie Duiker Penny A. Rudd Donna Skerrett James G. D. Pollard Carolyn Siddel Rifat Rifat Jennifer H. K. Ng Peter Georgius Lara J. Hererro Paul Griffin |
| author_sort | Ravi Krishnan |
| collection | DOAJ |
| description | Abstract Background Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain, leaving patients incapacitated for months to years. With no available vaccine or specific therapeutic for any alphaviral disease, and a growing economic and public health burden, there is a serious need for the development of specific therapies. Methods This study evaluated the safety and efficacy of pentosan polysulfate sodium (PPS) in subjects with RRV-induced arthralgia in a double-blind, placebo-controlled trial. Twenty subjects were randomized 2:1 to subcutaneous PPS (2 mg/kg) or placebo (sodium chloride 0.9%) twice weekly for 6 weeks. Safety evaluation included physical examination, concomitant medications, and laboratory findings. Efficacy assessments included change from baseline in joint function (hand grip strength and RAPID3) and quality of life (SF-36) at Days 15, 29, 39 and 81 after treatment initiation. Inflammatory and cartilage degradation biomarkers were exploratory endpoints. Results PPS was well tolerated, with a similar proportion of subjects reporting at least one treatment-emergent adverse event (TEAE) in the treatment and placebo groups. Injection site reactions were the most common TEAE and occurred more frequently in the PPS group. Dominant hand grip strength and SF-36 scores improved with PPS at all time points assessed, with hand grip strength improvement of 6.99 kg (p = 0.0189) higher than placebo at Day 15. PPS showed significant improvements versus placebo in adjusted mean relative change from baseline for RAPID3 Pain (p = 0.0197) and Total (p = 0.0101) scores at Day 15. At the conclusion of the study overall joint symptoms, assessed by RAPID3, showed near remission in 61.5% of PPS subjects versus 14.3% of placebo subjects. Additionally, PPS treatment improved COMP, CTX-II, CCL1, CXCL12, CXCL16 and CCL17 biomarker levels versus placebo. Conclusions Overall, the improvements in strength and joint symptoms warrant further evaluation of PPS as a specific treatment for RRV-induced and other forms of arthritis. Trial registration This trial is registered at the Australian New Zealand Clinical Trials Registry # ACTRN12617000893303 . |
| first_indexed | 2024-12-19T22:46:54Z |
| format | Article |
| id | doaj.art-2cf57ed3c4a34c8fa144800aab7950ee |
| institution | Directory Open Access Journal |
| issn | 1471-2474 |
| language | English |
| last_indexed | 2024-12-19T22:46:54Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Musculoskeletal Disorders |
| spelling | doaj.art-2cf57ed3c4a34c8fa144800aab7950ee2022-12-21T20:02:55ZengBMCBMC Musculoskeletal Disorders1471-24742021-03-0122111110.1186/s12891-021-04123-wPentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled studyRavi Krishnan0Melanie Duiker1Penny A. Rudd2Donna Skerrett3James G. D. Pollard4Carolyn Siddel5Rifat Rifat6Jennifer H. K. Ng7Peter Georgius8Lara J. Hererro9Paul Griffin10Paradigm Biopharmaceuticals Ltd.Paradigm Biopharmaceuticals Ltd.Institute for Glycomics, Griffith UniversityParadigm Biopharmaceuticals Ltd.Clinical Trials Unit, Barwon HealthSprings MedicalRich River Health GroupClinical Trials Unit (Griffith Health), Griffith University, Gold Coast, Australia and Gold Coast UniversitySunshine Coast Clinical ResearchInstitute for Glycomics, Griffith UniversityDepartment of Medicine and Infectious Diseases, Mater Misericordiae Ltd.Abstract Background Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain, leaving patients incapacitated for months to years. With no available vaccine or specific therapeutic for any alphaviral disease, and a growing economic and public health burden, there is a serious need for the development of specific therapies. Methods This study evaluated the safety and efficacy of pentosan polysulfate sodium (PPS) in subjects with RRV-induced arthralgia in a double-blind, placebo-controlled trial. Twenty subjects were randomized 2:1 to subcutaneous PPS (2 mg/kg) or placebo (sodium chloride 0.9%) twice weekly for 6 weeks. Safety evaluation included physical examination, concomitant medications, and laboratory findings. Efficacy assessments included change from baseline in joint function (hand grip strength and RAPID3) and quality of life (SF-36) at Days 15, 29, 39 and 81 after treatment initiation. Inflammatory and cartilage degradation biomarkers were exploratory endpoints. Results PPS was well tolerated, with a similar proportion of subjects reporting at least one treatment-emergent adverse event (TEAE) in the treatment and placebo groups. Injection site reactions were the most common TEAE and occurred more frequently in the PPS group. Dominant hand grip strength and SF-36 scores improved with PPS at all time points assessed, with hand grip strength improvement of 6.99 kg (p = 0.0189) higher than placebo at Day 15. PPS showed significant improvements versus placebo in adjusted mean relative change from baseline for RAPID3 Pain (p = 0.0197) and Total (p = 0.0101) scores at Day 15. At the conclusion of the study overall joint symptoms, assessed by RAPID3, showed near remission in 61.5% of PPS subjects versus 14.3% of placebo subjects. Additionally, PPS treatment improved COMP, CTX-II, CCL1, CXCL12, CXCL16 and CCL17 biomarker levels versus placebo. Conclusions Overall, the improvements in strength and joint symptoms warrant further evaluation of PPS as a specific treatment for RRV-induced and other forms of arthritis. Trial registration This trial is registered at the Australian New Zealand Clinical Trials Registry # ACTRN12617000893303 .https://doi.org/10.1186/s12891-021-04123-wRoss River virusPentosan polysulfate sodiumPainArthritisAlphavirus |
| spellingShingle | Ravi Krishnan Melanie Duiker Penny A. Rudd Donna Skerrett James G. D. Pollard Carolyn Siddel Rifat Rifat Jennifer H. K. Ng Peter Georgius Lara J. Hererro Paul Griffin Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study BMC Musculoskeletal Disorders Ross River virus Pentosan polysulfate sodium Pain Arthritis Alphavirus |
| title | Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study |
| title_full | Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study |
| title_fullStr | Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study |
| title_full_unstemmed | Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study |
| title_short | Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study |
| title_sort | pentosan polysulfate sodium for ross river virus induced arthralgia a phase 2a randomized double blind placebo controlled study |
| topic | Ross River virus Pentosan polysulfate sodium Pain Arthritis Alphavirus |
| url | https://doi.org/10.1186/s12891-021-04123-w |
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