Treatment Effects of Subcutaneous Injections of Pentosan Polysulfate Sodium vs Placebo in Participants With Knee OA Pain

This is a 2-stage, adaptive, randomized, double-blind, placebo-controlled, multicenter study that will evaluate the dose and treatment effect of PPS in participants with knee OA pain.

In Stage 1 (dose selection), approximately 468 participants will be randomised 1:1:1:1 to receive 1 of 3 PPS dose regimens or placebo for 6 weeks. A minimum of 96 participants (24 within each dose group) will be assigned to the Pharmacokinetic (PK) subset.

Participants in Stage 1 will be randomly allocated to receive:

* 1.5 mg/kg calculated for ideal body weight (IBW) PPS twice weekly * 2 mg/kg IBW PPS once weekly + placebo once weekly * 100/150/180 mg PPS if ≤ 65 kg/ ≥ 65 kg and ≤ 90kg/ \> 90kg IBW+ placebo once weekly * placebo twice weekly

In Stage 2, approximately 470 participants will be randomized 1:1 to receive the selected PPS dose regimen or placebo for 6 weeks. Approximately 150 participants (75 per group) will be assigned to the PK subset.

Participants in Stage 2 will be randomly allocated to receive:

* One of the 3 Stage 1 PPS dose regimens selected by the DMC * placebo twice weekly

The maximum duration for each participant is approximately 31 weeks, which includes:

* 7-week Screening Period from Day -45 to Day -1 * 6-week Treatment Period from Day 1 to Day 39 * 18-week Follow-up Period from Day 40 to Day 168