Monday, January 29, 2024

Results from a Phase-IIΔ Trial of Pleconaril and Ribavirin

This clinical trial represents an attack on T1D slightly different than anything I've blogged on before.

Pleconaril and Ribavirin are both antiviral drugs.  The idea here is that viruses either cause T1D or contribute to it, and that attacking viruses during the early honeymoon period will do something good.   Maybe delay the onset, extend the honeymoon, or even allow the long term survival of more beta cells to lower long term complications of T1D.  

I want to stress that this "virus causes T1D" hypothesis is just that: a hypothesis.  It is held by some researchers, but is not the consensus cause of T1D.  However, these researchers are moving forward assuming it is true, and therefore testing a prevention technique that is likely to work if it is true.  They had previously found low grade enteroviral infection in the pancreas of people recently diagnosed with T1D, and that motivated them to run this study.  

The study participants were between 6 and 15 years old and within 3 weeks of diagnosis.  These were early honeymooners.  The drug combination was in liquid form and drunk daily for six months, and then the people were followed for an additional six months, which is reported here.  Although they reported results in October, the study will continue for two more years and so we should get more results in the future.

The key finding was "During the 12-month study period, the relative decrease in C-peptide was 11% in the Pleconaril and Ribavirin group and 24% in the placebo group" (paraphrased).  So both groups dropped, but the treated group dropped much less.  See here for more discussion of why these sorts of results do not excite me.

This study was supported by JDRF, INNODIA and others.



The idea that a virus causes T1D, or triggers it, or make it worse, is widely held.  Many parents remember that their kids were sick just before or as part of their T1D diagnosis.  However, the causality part has not been proven.  Viruses may cause T1D, or they might trigger it (i.e. the person was going to get T1D anyway, and the virus just caused it to manifest now rather than next month), or it may be that early T1D symptoms are similar enough to the flu so that people get them mixed up, or it might be that after a diagnosis of T1D, parents suddenly connect it to the last illness the child had.

On the other hand, Coxsackie B viruses (a type of enterovirus) have been associated with T1D in previous population studies, and enteroviruses are known to target pancreatic islets.  There is another clinical trial which attempts to use a Coxsackie B vaccine to lower the rate of T1D, and a third using flu vaccine on people in the honeymoon phase.  So the causal part is certainly possible. 

About these anti-virals specifically, I think it is important to note that Pleconaril was never approved for use by the FDA because of side effects.  It was evaluated in the early 2000s.  Ribavirin is approved, but use in T1D would be "off label" and its label includes two black box warnings.

To me, these results seem similar to the Teplizumab in honeymooners results, although with the obvious caveat that this result is in a 100 person phase-IIΔ study, and the Teplizumab study was a 300 person phase-III study.  The Teplizumab honeymoon trial reported a difference of 0.13 pmol/ml while this study reported 0.16 pmol/ml.

But also, this study only shows preservation of beta cells (and not even complete preservation), and I usually only get excited about beta cell regrowth in the honeymoon phase.

Joshua Levy
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My kid has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.