Paradigm Biopharmaceuticals Ltd (ASX:PAR) has kicked off a multi-centre double-blind randomised Phase 2 clinical trial in Brazil comparing injectable pentosan polysulfate sodium (iPPS) to placebo in ‘ultra rare’ mucopolysaccharidosis type VI (MPS VI) patients.
The primary objective of the study is to evaluate the safety and tolerability of iPPS in subjects with MPS VI at 6, 12, and 24 weeks.
Once the data from the study is complete, the company plans to meet with key regulatory bodies in jurisdictions where the MPS disease is most prevalent to determine if its Phase 2 clinical data is sufficient for registration due to the high unmet medical need.
“Fantastic milestone”
Paradigm’s global head of safety and head of the MPS program Dr. Michael Imperiale said: “Enrolling thirteen participants in a blinded controlled study in this rare disease is a fantastic milestone for Paradigm.
“Paradigm and the key opinion leaders associated with this study are encouraged about the potential of iPPS addressing this critical unmet medical need in the MPS community.
“We look forward to the completion of the study and providing further updates as the study reaches completion."
Commercial strategy
Paradigm's commercial strategy is to partner this indication, with a commercial transaction expected to generate non-dilutive funding for the MPS Phase 3 clinical trial, should one be required.
For completeness, the MPS VI Phase 2 clinical trial is a separate program from Paradigm's Phase 3 clinical program relating to improvements in pain and function in people afflicted with knee osteoarthritis.
Two separate reviews of subjects aged 16+ and nine to 16 years of age have been completed with no serious adverse events reported in both cohorts, allowing for inclusion of subjects five-plus years of age into the study.
Early therapeutic intervention to improve symptoms is critical in this population of MPS VI sufferers, who continue to experience joint pain and stiffness that limits their mobility and function despite enzyme replacement therapy.
Trial design
Brazil has one of the highest rates of MPS VI.
With the Phase 2 study, randomised, double-blind, placebo-controlled study is evaluating the safety and tolerability of iPPS in treating subjects with MPS VI who exhibit pain and functional deficiency due to musculoskeletal symptoms associated with the underlying disease.
Study endpoints
Following completion for all study participants of the 24-week treatment period, Paradigm will assess a number of key secondary and exploratory endpoints, including effect of iPPS on:
- pain and function (mobility);
- urinary GAG levels;
- walking-related pain;
- quality of Life, activities of daily living, subject/parent global impression of response to therapy; and
- pulmonary function.
The mucopolysaccharidoses and related disorders belong to a group of more than 40 inherited lysosomal storage diseases.
Lysosomes are the recycling centres of all cells that break down excess or worn-out cell parts with their digestive enzymes.
Mucopolysaccharidoses disorders are due to errors with one of the enzymes that break down and recycle glycosaminoglycans (GAGs), previously known as mucopolysaccharides.
As these waste products cannot be eliminated, they accumulate within the lysosomes of virtually every cell type within the body, causing cells, tissues, and organs to function abnormally, leading to progressive damage.
The heart, bones, joints, respiratory system, and central nervous system, including cognitive function, may eventually be affected.
In most cases, symptoms are not apparent at birth, but emerge gradually as a result of defective lysosomal storage and resulting cell damage over time.
Eleven different types of mucopolysaccharidosis have been described, where each is the result of a deficiency in one of the enzymes in the glycosaminoglycan degradation pathway.