Finally, the long-awaited Stanford University phase 3 Oral Vancomycin for PSC trial results are available. In general, the results for children look excellent. For adults, the results look also fairly good (maybe we could say 50% had actual improvement seen in MRCP, and ~80% has improvement in blood tests i.e. LFTs).
“Primary Sclerosing Cholangitis With Oral Vancomycin by the Study of Its Antimicrobial and Immunomodulating Effects (PSC)”
ClinicalTrials Identifier: NCT01802073
Phase 3
20 adults started the trial, 9 completed the trial.
14 children started, and 9 completed.
Results:
Primary: Count of Participants With Elevated Alanine Aminotransferase (ALT) at Baseline and With Clinically Significant Improvement at Month 3:
Children: 10/10 (i.e. everybody had improvements)
Adults: 6/9 (i.e. 6 out of 9 tested had this positive success)
Primary: Count of Participants With Elevated Gamma-glutamyltransferase (GGT) at Baseline and With Clinically Significant Improvement at Month 3 [ Time Frame: Baseline; Month 3 ]
Children: 8/8
Adults: 6/9
Primary: Count of Participants With Elevated ALT and/or GGT at Baseline and With Clinically Significant Improvement at Month 3 [ Time Frame: Baseline; Month 3 ]
Children: 10/10
Adults: 8/10
Primary: Count of Participants With Abnormal Magnetic Resonance Cholangiopancreatography (MRCP) Imaging at Baseline and With Clinically Significant Improvement at Year 1 [ Time Frame: Baseline; Year 1 ]
Children: 6/8
Adults: 4/8
Primary: Count of Participants With Abnormal Liver Biopsies at Baseline and With Clinically Significant Improvement at Year 1 [ Time Frame: Baseline; Year 1 ]
Children: 3/3
Adults: 0/0 (i.e. nobody evaluated)
Primary: Count of Participants With Abnormal MRCP and/or Liver Biopsy at Baseline and With Clinically Significant Improvement at Year 1 [ Time Frame: Baseline; Year 1 ]
Children: 10/10
Adults: 4/9
Thanks for posting the results/link. My wife just (unsuccessfully) asked her hepatologist if she can try vanco. It was our second time trying to convince her, but before all we had was anecdotal evidence to show her. We live in the NYC/NJ area, is there anyone who knows a hepatologist /GI who is willing to try patients on oral vanc in the area? Some background on my wife- she has UC (diagnosed 2007), and was diagnosed with PSC after getting cholangiocarcinoma (2016) which she had resected (the PSC was diagnosed during the partial liver resection).
thanks,
FDA awards 12 grants to fund new clinical trials to advance the development of medical products for the treatment of rare diseases
“ * Arizona State University-Tempe Campus (Tempe, Arizona), Keith Lindor, phase 2 study of oral vancomycin for the treatment of primary sclerosing cholangitis – $2 million over four years”
There are several ongoing Vanco trials (including one phase 4 trial) by different teams. They have their own study design, and limitations that are result of limited funding. Phases are somewhat descriptive of the stage of testing (eg phase1 to ensure safety of treatment, phase 3 is typically double blind randomized etc) but these university sponsored trials are not really FDA compliant in the sense that they would lead to FDA approval. Such approval would require expensive trials and some consensus and agreement with FDA how to measure success in PSC trials.
Great to have the results, but as mentioned above it is disappointing that more than half of the adults didn’t complete the trial. Makes the results hard to interpret. At this point I think we really need larger randomized trials of vancomycin in adults that include imaging outcome measures as well as liver enzymes.
Not completed: 5 children, 11 adults.
(children) (adults)
Lost to Follow-up 0 1
Non-compliant 4 2
Withdrawal by Subject 1 1
Physician Decision 0 7
I agree that it is hard to make clear conclusions, but in anycase, at least 4 adults seemed to have reversal of PSC as seen in MRCP imaging and total 8 seemed to have significant LFT improvement. No adverse effects for adults - I would expect some non-participating PSC patients have such events, so that is great news too.
Other treatment options (e.g. Urso) also seem to improve LFTs but they didn’t seem to otherwise stop or reverse PSC.
Personally I’m most excited about the MRCP improvement results. This gives further confirmation about Vanco.
Large-scale Vanco trial (leading to FDA approval) would be great, but that is difficult. It is expensive and many people would rather take Vanco instead of risking getting placebo in double-blind trial.
You’re absolutely right, I know I wouldn’t want my partner to get the placebo! Such a difficult issue when it comes to clinical trials in rare diseases. I agree that the results are promising. Hopefully they will be presented/published soon so we can see the details regarding the drop outs.
We see Dr Brett Fortune at Weill Cornell in NYC. He will prescribe. He’s wonderful. Tell him Joanne and Emily sent you. We were referred by a father on this site and will forever be grateful. Vanco has been a miracle for my daughter.
I have made some comments before about this study, mainly regarding adult part.
Results were presented in a very strange way, biochemistry data only at month 3 and imaging data only at year 1. Where is biochemistry data at one year point? Those data should be easily available. I didn’t do a power analysis to determine whether they have enough participants to run statistic tests, particularly for MRCP and biopsy comparison. I kind of doubt it.
Why phase 3? This is technically a phase 2 clinical trial. I guess that phase 3 is their own definition.
Again, I’m only talking about adults data. Kids are totally different.
Hello DHZ! The results posted here are not published results, hence the weirdness. We’ll need to wait to see the published article, before we can draw any conclusions. Also, phase 3 refers to the aim of the study (it’s not a regular FDA phase 3 study).
This presentation provides some additional insight into the results of his most recent clinical trial as well as interesting statistics for all of the PSC patients he has treated with vanco.
Update on the above-mentioned Arizona State University FDA-sponsored Vancomycin trial.
It is now official:
Phase 2 and phase 3 trials, to be completed by 2022. These trials will have 103 participants (at least in Arizona,Minnesota, and Canada). Not sure if this trial would help in FDA approval.
Primary Outcome Measures :
Alkaline phosphatase [ Time Frame: 18 months ]
Secondary Outcome Measures :
Fibroscan, cholangiography [ Time Frame: 18 months ]
So, 103 total, then, about 50 with vanco. I predict there will be positive results regarding the primary outcome measures, but I’m not sure about the secondary outcome measures as this would be a very heterogeneous patient group. FDA approval would be questionable. I guess it very depends on the results of the secondary outcome measures. And that Vanco-resistant bacteria thought is a big no-no for many clinicians.
