Paradigm Biopharmaceuticals Ltd (ASX:PAR) has initiated a Phase II clinical trial of subcutaneous injectable Pentosan Polysulphate Sodium (iPPS), in patients with the ultra-rare orphan disease Mucopolysaccharidosis Type 1 (MPS-1).
The Phase II trial will be Paradigm’s first in MPS-I patients and will investigate treatment in a population, including pediatric patients.
Potential adjunctive therapy
Paradigm chief executive officer Paul Rennie said: "It is personally gratifying to see Paradigm’s study successfully progressing in what is an ultra-rare disease state where patients still experience unmet need.
“The data collected from the Phase 2 trial will be vital to support Paradigm’s future regulatory filings and applications for the development of PPS as a potential adjunctive therapy to Enzyme Replacement Therapy (ERT) treatments.
“Our MPS programs will treat subjects as adjunct to ERT as well as previously bone marrow transplanted patients who may or may not remain on ERT.
Orphan drug indication
“I am pleased to report to our shareholders that Paradigm is making significant progress in the clinical development of PPS in both of our two programs of osteoarthritis (Zilosul®) and the rare disease of MPS.
“It is important to note both the US FDA and EU EMA have confirmed MPS is an orphan indication and as such the commercial advantage of an orphan drug is the seven-year regulatory exclusivity awarded to orphan drugs.”
Dr Ketteridge and Dr Bratkovic to lead trial
The study will be conducted at the Adelaide Women’s and Children’s Hospital (WCH) with Dr David Ketteridge, the principal investigator and Dr Drago Bratkovic, the head of the metabolic clinic, leading the clinical trial.
Dr Ketteridge is a paediatrician and metabolic physician at the Adelaide WCH, and has extensive experience in treating Lysosomal Storage Disorders.
The first patient to be enrolled in the study has completed screening and has received the first dose of iPPS.
Rare inborn metabolic disorder
MPS-I is a rare inborn metabolic disorder caused by a genetic defect in the catabolism of two glycosaminoglycans (GAGs): heparan sulphate and dermatan sulphate.
Disorders in the catabolism of these GAGs interfere with cellular function, resulting in abnormal bone development, growth retardation, cardiac and respiratory problems, and sometimes cognitive impairment.
The current treatments, ERT and/or Hematopoietic Stem Cell Therapy (HSCT) are available and indicated for people diagnosed with MPS-I to treat the underlying disease by reducing the accumulation of glycosaminoglycans (GAGs).
Study details
Paradigm’s open-label Phase II trial will primarily assess the safety of Pentosan Polysulphate Sodium (PPS) in patients with MPS-I.
The secondary objectives will be to evaluate if PPS can successfully alleviate pain and functional symptoms in MPS-I patients who have received ERT and/or HSCT, where these patients continue to have residual musculoskeletal symptoms (joint pain, muscle pain and limited range of motion in various joints).
Patients will be dosed for 48 weeks and will be evaluated according to incidence of treatment-emergent adverse events (TEAEs) and changes in clinical laboratory data, pain and function.
The open-label study will recruit up to 10 participants, both male and female, aged five years or above, who meet specific inclusion criteria.
Participants will be sequentially assigned to one of two dosing cohorts (0.75mg/kg and 1.5mg/kg) and the study drug will be administered via subcutaneous injection weekly for the first 12 weeks and then every second week until week 48.
Paradigm previously in-licensed the MPS indication from Icahn School of Medicine at Mount Sinai, New York.