Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study

Krishnan R, Duiker M, Rudd PA, Skerrett D, Pollard JGD, Siddel C, Rifat R, Ng JHK, Georgius P, Hererro LJ, Griffin P · BMC Musculoskeletal Disorders

The primary endpoint was safety and tolerability; every efficacy measure was secondary, and the protocol planned no formal hypothesis testing of treatment effect. Dominant-hand grip strength rose 6.99 kg more than placebo at day 15 (p=0.0189), the one hand and one timepoint at which the groups separated, and placebo grip strength had dipped below its own baseline at that visit before rising to clear the same clinically important threshold by day 81. RAPID3 pain (-28.05% against +9.9%, p=0.0197) and RAPID3 total (p=0.0101) separated at day 15; RAPID3 function and global estimate did not, and the dedicated NRS-11 pain scale showed no significant difference at any timepoint. Of 42 biomarkers measured, serum COMP (p=0.0489), urinary CTX-II (p=0.017) and three chemokines fell further than placebo while CXCL16 rose. Injection-site reactions were the most common adverse event and were more frequent on PPS.

Population

20 adults with persistent joint pain after Ross River virus infection, Australia

Intervention

Subcutaneous PPS 2 mg/kg twice weekly for 6 weeks

Comparator

Placebo (0.9% sodium chloride), randomized 2:1

Limitations

Thirteen participants on PPS and seven on placebo, with no sample-size calculation, no planned hypothesis testing and no correction across the measures reported. Randomisation left the arms in different severity bands: 53.8% of the PPS group began in the high-severity RAPID3 category against 28.6% of placebo. Biomarkers were measured in the 13 participants with a usable baseline, 8 on PPS and 5 on placebo. 93.5% of injection-site reactions occurred in the PPS group, one participant stopped drug for injection-site erythema, and transaminases rose on PPS to 1.4x the upper limit of normal for AST and 2.7x for ALT by day 39 before falling back. The disease is a post-viral arthritis rather than osteoarthritis. Funded by Paradigm Biopharmaceuticals, with three authors employees of the sponsor.