Paradigm Biopharmaceuticals Ltd (ASX:PAR) announced today that the first safety review meeting of the Data Monitoring Committee (DMC) for the pivotal PARA_OA_002 clinical trial was conducted on December 20.
The DMC is responsible for assessing safety and efficacy during the conduct of PAR’s PARA_OA_002 study, as well as ensuring the validity and scientific merit of the trial. It concluded that the PARA_OA_002 clinical trial should proceed without modification.
PAR’s Phase 3 Pivotal PARA_OA_002 clinical trial is a randomised, double-blind, placebo-controlled, multicentre (US/AU/UK/EU/CA) study that will evaluate the dose and treatment effect of injectable pentosan polysulphate sodium (iPPS) in participants with knee osteoarthritis (kOA) pain.
“The DMC is a formal review process, and a written response has been received by the company. This is a positive outcome for Paradigm that the early safety data from the pivotal PARA_OA_002 clinical trial has been reviewed by the DMC and it was recommended to continue without modification,” Paradigm managing director, Paul Rennie said.
“Injectable PPS has been well tolerated throughout all of Paradigm’s clinical programs, including real-world evidence with treatment of over 600 participants via the TGA Special Access Scheme.”
Evaluating iPPS
The purpose of the PARA_OA_002 study is to measure the change in pain and function with subcutaneous injections of iPPS compared with subcutaneous injections of placebo in participants with knee osteoarthritis (kOA) pain.
This is a 2-stage, adaptive study that will evaluate the dose and treatment effect of iPPS in participants with kOA pain.
Stage 1 comprises phase 2b dose selection, with approximately 468 participants randomised to receive 1 of 3 iPPS dose regimens or placebo for six weeks. The primary objective of stage 1 is to identify the minimal effective dose that will be used in stage 2 and in Paradigm’s confirmatory trial. The selected dose is based on an optimal balance of efficacy and safety.
Participants in stage 1 will be randomly allocated to receive one of the following:
- 1.5 mg/kg calculated for ideal body weight (IBW) iPPS twice weekly
- 2 mg/kg IBW iPPS once weekly + placebo once weekly
- Fixed doses
o 100 mg iPPS for ≤65 kg IBW once weekly + placebo once weekly, or
o 150 mg iPPS for >65 to ≤90 kg IBW once weekly + placebo once weekly, or o 180 mg iPPS for >90 kg IBW once weekly + placebo once weekly
- Placebo twice weekly
In stage 2 (phase 3), approximately 470 participants will be randomised 1:1 to receive the selected iPPS dose regimen or placebo for 6 weeks. Participants in stage 2 will be randomly allocated to receive:
- One of the 3 stage 1 iPPS dose regimens selected by the DMC, or
- Placebo twice weekly
The primary endpoint in the pivotal study is a change from baseline at day 56 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain. Secondary outcomes include change from baseline at multiple time points out to day 168 in WOMAC pain and function, Patient Global Impression of Change (PGIC), and Quality of Life (QoL).
“I look forward to updating our shareholders in calendar year 2023 on the progress of Paradigm’s exciting OA clinical program with further PARA_OA_002 updates, as well as 6-month data from our PARA_OA_008 clinical trial exploring the disease modifying potential of iPPS,” Rennie said.
About Paradigm
Paradigm Biopharmaceuticals Ltd. is a late-stage drug development company driven by a purpose to improve patients’ health and quality of life by discovering, developing, and delivering pharmaceutical therapies. Paradigm’s current focus is developing injectable (subcutaneous) pentosan polysulfate sodium (iPPS) for the treatment of diseases where inflammation plays a major pathogenic role, indicating a need for the anti-inflammatory and tissue regenerative properties of PPS, such as in osteoarthritis (phase 3) and mucopolysaccharidosis (phase 2).