Stanford Vancomycin trial phase3 results available

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,

Somewhat related:
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm621490.htm

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”

I don’t understand why it’s a phase 2 again? After all a phase 3 study, also done in the US by a University, just ended a week ago?

Is there any color as to why repeat MRCP and Biopsies were not done at end of study rather than just after 1 year?

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.

The results show the following:

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.

Thank you. We will seek him out

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). :slight_smile:

Thanks for the insider information. I never talked to anyone at Stanford group directly so all my comments are based on their publications only.

Thanks for the update, Ted.

Here’s Dr. Cox’s presentation at the Cincinnati Children’s Center for Autoimmune Liver Disease last month: https://cchmcstream.cchmc.org/MediasiteEX/Play/163d881253c347be89c22bd8f3798ff71d

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 :

  1. Alkaline phosphatase [ Time Frame: 18 months ]

Secondary Outcome Measures :

  1. Fibroscan, cholangiography [ Time Frame: 18 months ]
1 Like

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.

Liver Meeting 2018 conference is this week in San Francisco. This Vanco article below is also from Stanford U related people, but this may involve other patients too (other than phase3 trial).

“Long-Term Treatment with Oral Vancomycin for the Treatment of Primary Sclerosing Cholangitis and Inflammatory Bowel Disease”

“Methods: Pediatric and adult patients with PSC at two major medical centers were treated with OV over a 15-year period. Clinical symptoms, laboratory values, radiological studies, and liver biopsies were documented for 12 months after initiation of OV.”

" Results: A total of 59 subjects (64% male) with a median age of 13.5 years (1.5 - 44) at diagnosis were enrolled. Forty-five patients were pediatric patients (<18 years). Ninety-four percent had concomitant IBD (92% UC, 8% Crohn’s disease). Patients received OV at a dose of 50 mg/kg/day divided 3 times per day if weight < 30 kg and 500 mg 3 times per day if ≥ 30 kg. Patients were treated for a median of 2.9 years. Forty four percent had normalization of GGT, 59% had normalization of ALT, and 20% had normalization of ALP. All patients had a reduction in ALT, and 91.5% had a reduction in GGT. Seventy-six percent had follow-up MRI while on OV, and all patients had either stable or improved hepatic stricture, periductal inflammation, biliary dilatation, and/or fibrosis. Twenty-eight patients had liver biopsy post-OV treatment, and all had either stable disease or improvement in inflammation. Sixty-nine percent of patients had improvement in abdominal pain and diarrhea related to IBD. No subjects developed hepatobiliary or colorectal cancer. One patient had a liver transplant 8 years after starting vancomycin treatment, however he had advanced cirrhosis at time of initiation of vancomycin. None of the patients developed side effects. There was no significant difference in response to vancomycin for age, sex, severity of liver fibrosis, and small compared to large duct disease.

Conclusion: The long-term use of OV in PSC is associated with improvement in liver biochemistries and stabilization or improvement in histological and cholangiographic abnormalities."

https://plan.core-apps.com/tristar_aasld18/abstract/3b9b2f3af8aefb4e9fba71511db0fb86

Does anyone know what brand(s) of Vancomycin were used in this extremely promising study? This was a fifteen year long study? Am I understanding this correctly? Wow. Seems pretty definitive.

I spoke with one of the Stanford docs about this few years ago. She mentioned that brand differences were an issue and they are aware of that. Trial was not sponsored ie patients had to buy their own Vanco…so I’m sure that various brands were used.

1 Like

That introduces such a profound variable. Wow.

Thanks Ted.