Paradigm Biopharma weathers seasonal change to complete recruitment for Ross River virus study

Paradigm Biopharmaceuticals (ASX: PAR) has completed the recruitment stage of its phase 2a clinical trial in participants with persistent ‘Ross River virus (RRV) induced arthralgia’, also known as painful joints, treated with the company’s flagship drug candidate injectable pentosan polysulfate sodium (iPPS).

The RRV is a mosquito-borne infectious disease from the “alphavirus genera” genus subgroup, also shared by other viruses such as the Chikungunya Virus. Diseases such as RRV and Chikungunya cause similar debilitating symptoms of joint pain, fever, headache, conjunctivitis and rash.

According to researchers from the University of Nebraska Medical Center in Omaha, the disease course is divided into an acute stage, lasting approximately one week, and a chronic stage, also known as the persistent stage, which can last “from months to years”.

Both RRV and Chikungunya are typically characterised by an “influenza-like illness” and polyarthritis – a relatively severe type of arthritis that involves 5 joints simultaneously. The term “arthralgia” refers to non-inflammatory joint pain whereas “arthritis” refers to inflammatory joint pain.

The virus is endemic to Oceania and the South Pacific will all previously reported cases originating in mainland Australia and Tasmania, the island of New Guinea, Fiji, Samoa, the Cook Islands, New Caledonia and several other islands in the South Pacific.

Trialling iPPS in treating RRV-induced arthralgia

Paradigm has said that it has finalised recruitment for the clinical trial while having to overcome various seasonal difficulties to “achieve good recruitment rates in 2017 and earlier this year”.

The company has decided to conduct its trial in the Australian state of Victoria but requires a minimum number of suitable candidates in order to successfully carry out the trial into iPPS.

Given the current rate of applications, Paradigm has confirmed that it intends to cap its participant recruitment rate to 20 instead of 24 to “effectively meet the clinical milestones without escalating trial maintenance costs or delaying trial read-out”.

Paradigm was forced into capping trial participants due to unexpected seasonal conditions influencing its ability to recruit a suitable number of candidates – a development the company has moved to mitigate by adjusting its clinical trial criteria.

Raining on the iPPS parade

According to Paradigm, a lack of rainfall in the eastern states of Australia last year and a parallel reduction in reported mosquito outbreaks have contributed to slow recruitment of participants that satisfy the trial’s inclusion criteria.

Scientific records show that the high RRV infection rates observed in 2017 have not been repeated in 2018 which has, in turn, led to a lower incidence rate and more difficulty in sourcing trial candidates.

Paradigm said that “the seasonal and epidemiological challenge was particularly evident in rural Victoria, where the number of notified cases were nearly 20-fold lower in 2018 (98 notifications) compared to 1,921 notifications in 2017.”

However, despite its recruitment difficulties, the company said that it is “satisfied” that 20 participants can meet the outcome objectives of demonstrating safety and affecting primary symptoms in its pilot phase 2a study; and has committed to completing the trial before year-end.

“Strategically, this pilot study is aimed at providing the clinical evidence for the design of a larger clinical trial in Chikungunya Virus (CHIKV) induced arthralgia,” said Paul Rennis, CEO of Paradigm Biopharmaceuticals.

New paradigm in treating alphaviruses

According to scientific research, CHIKV causes more than 3 million infections each year with outbreaks being reported in parts of Africa, Europe and southeast Asia.

In 2013, the Centers for Disease Control and Prevention (CDC) in the US said that for the first time, CHIKV was found in the Americas, the Caribbean, South and Central America and North America. The surprise announcement put US authorities on alert and looking into options to mitigate the problem although progress in creating adequate countermeasures has been slow over the past 5 years.

The growing incidence rates of alphaviruses such as RRV and Chikungunya have encouraged Paradigm to commence its trial to verify the efficacy of iPPS upon alphaviruses. Just recently, the company said that “a lack of anti-viral agents, vaccines or effective pharmaceutical agents to treat the debilitating effects of CHIKV makes iPPS a valuable product for this unmet medical need.”

In addition to the clinical data from the RRV phase 2a clinical trial, Paradigm said it is collaborating with the Institute of Glycomics at Griffith University to investigate the effects of iPPS in animal models of CHIKV infection, a move that would further support future clinical trial design.