Issue 5 - October 2022
Welcome! In this issue: • From the Registry Director • The Clinical Trial Landscape in PSC • Current International PSC Research • The ChiLDRen Study • Gilead's PRIMUS Trial Terminated • Patient-friendly Clinical Trial Design • Highlights of the 2022 International Liver Congress • Meet PSCP's Ruth-Anne Pai, PhD • Clinical Trials Are Recruiting
From the Registry Director
Dear Registry Participants,
Whether you are a person living with PSC, or the relative, friend, or caregiver of one, you probably never stop searching to understand how research into PSC treatments is progressing.
In this newsletter, you will find a review of PSC Partners’ recent webinar about current trials; highlights of the annual conference session on the international PSC research landscape; information about a current, exciting study for children and young adults; an invitation to submit ideas and concerns about trials that we can take to those conducting clinical trials; and more.
You can also explore trial information at your convenience on the Registry website. The Registry team maintains a list of currently enrolling PSC clinical trials and studies on the “Clinical Trials” webpage and provides links to detailed information about them.
On the same page, you can find links to more general information, such as a map of trial locations and an explanation of clinical trial “phases.” A demonstration of how to find the trial page and navigate the map resource is included in a short Registry video tour that can be found here (time stamp 3:40).
An important function of the Registry is to assist in connecting PSC patients with clinical trials or studies for which they may be eligible. Based on your answers to the patient surveys, you may receive occasional emails with information about a clinical trial that is recruiting PSC patients.
PSC Partners encourages all patients to learn as much as possible when making decisions about joining a study or trial. That is why we created a new Registry feature, the “Publications Related to Clinical Trials in PSC” page, located in the Resources section of the website. Here we suggest ways of evaluating studies, articles, and information related to ongoing clinical trials.
Regardless of whether you are interested in or eligible for a trial, staying abreast of PSC research progress will keep you informed about new treatments and discoveries. Your engagement and your input about study design and methods is valued.
“Together, we are creating a world where a PSC diagnosis comes with a cure!”
On behalf of the Registry team,
Rachel Gomel, Director, PSC Partners Patient Registry
The Clinical Trial Landscape in PSC - Overview of a PSC Partners Webinar
One of the recent PSC Partners post-conference webinars brought together the current clinical trial perspectives in PSC. Numerous clinical trial updates were presented at the September 21 event, “The Clinical Trial Landscape in PSC: Current and New Opportunities for Patients.”
A panel of experts discussed ongoing PSC studies and clinical trials. The goal of this webinar was to familiarize the PSC community with what clinical trial participation entails, with the different types of clinical trials that are being conducted, and on ways we can advance towards new treatments and the much anticipated cure.
Trials/studies presented were:
Brigham and Women’s Hospital (DINER nutrition study)
Chemomab Therapeutics (SPRING study of novel antifibrotic, anti-inflammatory, biologic drug CM-101)
CymaBay Therapeutics (study of Seladelpar for impact on PSC disease progression)
Escient Pharmaceuticals (trial of drug EP547 for pruritus)
Gilead Sciences (PRIMIS study of Cilofexor for fibrosis) - This trial was terminated after the webinar; see details below.
HighTide Therapeutics (study of HTD180 drug, also known as berberine ursodeoxycholate, with anticipated anti-inflammatory, anti-cholestatic, and antifibrotic properties)
Mayo Clinic (oral vancomycin trial)
Mirum Pharmaceuticals (VISTAS trial of volixibat for pruritus)
Pliant Therapeutics (INTEGRIS-PSC trial of the antifibrotic drug PLN-74809)
You are invited to watch the recorded presentations and learn about these ongoing or recently completed trials.
Current International PSC Research: Updates from the 2022 PSC Partners Conference
An update on international PSC research activity was one of the most popular sessions at the June 2022 PSC Partners conference. Conference co-host Dr. Joshua Korzenik moderated the presentation, titled “International PSC Research: Updates Across Spectrum – From IBD & Fibrosis to Genetics & Environment.”
This informative conference session is online and includes the following three presentations and a question-and-answer segment.
“Fibrosis and Fibrotic Mechanisms in Primary Sclerosing Cholangitis,” presented by Richard Green, MD, of Northwestern University Feinberg School of Medicine (time stamp: 3:19)
“The Norwegian PSC Research Center…an Update from Oslo and Bergen,” presented by Tom Hemming Karlsen, MD, PhD, Norwegian PSC Research Center (time stamp: 20:19)
“PSC and IBD. A Close Relationship. Siblings or Distant Cousins? What We Can Learn from It,” presented by Joshua R. Korzenik, MD, Brigham and Women’s Hospital (time stamp: 38:57)
The Q&A portion was moderated by Joel Pekow, MD, of University of Chicago Medicine. Kirsten Muri Boberg, MD, PhD, of the Norwegian PSC Research Center, joined Drs. Green and Korzenik to answer questions submitted by conference participants (time stamp: 58:03).
You are encouraged to check out what’s new in PSC research and find out the ways in which it is gaining momentum towards developing better treatments for people living with PSC.
The ChiLDReN Study: an Opportunity for Children and Young Adults with PSC
The Childhood Liver Disease Research Network (ChiLDReN) is a collaborative team of medical professionals, patient support organizations, and the National Institutes of Health (NIH). With clinical sites and research laboratories in the U.S., Canada, and the United Kingdom, ChiLDReN sponsors a number of natural history studies focused on rare cholestatic liver diseases, including a new study on PSC in the pediatric and young adult PSC population.
“Primary Sclerosing Cholangitis in Children,” is an observational, 10-year prospective natural history study funded by the NIH.* Study investigators are seeking 700 young PSC patients at nine North American sites.
Those aged 2 – 25 at time of screening with a diagnosis of either large-duct PSC or small-duct-only PSC may be eligible if they meet the other specific criteria. Those currently taking ursodeoxycholic acid or oral vancomycin for treatment of their PSC may remain on it.
The purpose of the ChiLDReN study is to collect medical and other data to learn more about PSC, how it progresses, and identify factors that may cause the disease to progress more quickly; and to ask questions about how PSC symptoms affect a child's life to learn more about its impact on their daily functioning.
Also, participants who are seen at one of the clinical sites will be asked to contribute information, DNA, and other specimens. The information and specimens will be available to investigators to carry out approved research aimed at learning more about the possible causes and long-term effects of PSC.
Detailed information about the study and participating sites can be found at clinicaltrials.gov, including site locations, the site’s contact person, and their contact information (scroll down to “Locations”). Please contact them directly for specific study information.
Given the rarity of PSC in young people, it is imperative that investigators work together across treatment centers in order to have study cohorts that are large enough to draw statistically sound conclusions. PSC Partners is extremely grateful to the investigators working on this study for their collaborative approach to gathering this important data, and to the NIH for funding the study.
*through the National Institute of Diabetes and Digestive and Kidney Diseases program (NIDDK)
Gilead's PRIMUS trial is terminated early
On September 27, 2022, Gilead Sciences announced the early termination of the PRIMUS study, its phase 3 study of the investigational drug Cilofexor. Although there were no reported safety issues, the trial evidence to date did not show that the drug was effective for PSC. The decision to stop the trial was based on the results reached after the first 160 participants had completed Week 96 of the trial. The primary endpoint was improvement of fibrosis measured with a biopsy. Investigators saw no benefit to continuing the trial. You can read the Gilead statement here.
This is certainly disappointing news. However, a “failed” trial is not a failure if lessons are learned that prove helpful going forward. Especially when a disease mechanism is unclear, such as in PSC, an unsuccessful trial can provide clarity regarding the disease process. Other times, the trial design may prove faulty even though carefully planned; such mistakes are informative to future trials and may even provide new information about the disease itself.
PSC Partners continues its collaboration with Gilead and hopes that they will persist in seeking a treatment for PSC.
If you took part in the PRIMUS study, you are deeply appreciated. The research process is lengthy, difficult, and sometimes disappointing; however, without study participants, it would go nowhere. Patients willing to participate in clinical trials are key to the ultimate goal of treatments and a cure for PSC.
For more information, please contact Gilead Public Affairs at public_affairs@gilead.com.
How can clinical trials become more patient friendly?
Your input is needed!
PSC Partners frequently communicates with PSC researchers and drug developers about patient-friendly trial design. Too often, the burden of travel, invasive testing, too-stringent inclusion/exclusion criteria, and more, limit the number of patients willing to enroll in a trial, which naturally slows the pace of research.
Have you ever participated in a clinical trial? Wanted to but didn’t meet the inclusion criteria? Met the criteria but found the requirements too burdensome or the potential risk too high? We want to hear from you!
Some of you may have participated in a trial and had a positive and rewarding experience. We would love to hear from you, too. It would help to know what the trial team did right.
Your comments about both positive and negative trial experiences as well as concerns or limitations that may keep you from enrolling in a clinical trial are valued. You can contribute to the patient voice in shaping patient-friendly trials.
You can share your thoughts by email at registrycoordinator@pscpartners.org OR, if you prefer to be anonymous, you can fill out this two-question Google Survey. If you email, Sharon or Rachel will be responding to you.
Some points you may want to address:
Considerations about inclusion and exclusion criteria, which are meant to ensure trial safety and uniformity in testing
Thoughts on the trial drug
Thoughts about frequency and type of testing
Logistics such as travel frequency and time spent at the trial site
Comments on health impact incurred by the trial
Communication quality regarding consent documents, your role in the trial, and/or availability of the trial team to answer questions
Compensation for expenses incurred or payment for your time
Access to study results
Fears, concerns, and/or positive experiences
The chart below shows the percentage of Registry Clinical Survey respondents who were currently participating in a clinical trial related to PSC at the time they completed the survey (blue bar) or who had previously participated in a PSC clinical trial or donated a biospecimen for PSC research (red bars). The green bars signify the percentages of respondents who indicated that they are willing to be contacted in the future about PSC trials and biospecimen donation for PSC research. Receiving information about trials and studies does not obligate participants to enroll or donate.
The relatively low figures for current or past participation raise some questions:
Are too many patients not a match for clinical trials?
Are researchers unable to reach those who could be a match?
Are clinical trials not easily accessible to people with PSC?
No matter what the reasons are, these figures show that people with PSC are very willing to participate in research.
Thank you for taking a few minutes to email us at registrycoordinator@pscpartners.org OR respond to the anonymous Google survey with your comments. The PSC community has been sharing thoughts and concerns through surveys and discussions. PSC Partners brings your de-identified input to the attention of researchers and trial developers when reviewing trial protocols, with the intent of helping them design trials that are as patient friendly as possible.
Highlights of the 2022 International Liver Congress
PSC Partners Board Member Jesse Kirkpatrick, PhD, has chosen to pursue a career focused on PSC, following a family member's PSC diagnosis. Now a Harvard medical student and postdoctoral researcher at the Massachusetts Institute of Technology, Dr. Kirkpatrick is conducting PSC research with the goal of answering key unsolved questions in PSC.
He recently attended the 2022 International Liver CongressTM (ILC), which was hosted in London by the European Association for the Study of the Liver (EASL), and shared a few of the highlights with the Registry team.
Dr. Kirkpatrick described the recently updated EASL Clinical Practice Guidelines* on sclerosing cholangitis as “one of the most relevant” topics discussed. The EASL PSC guidelines were published in the Journal of Hepatology in September 2022 and a brief summary, including EASL's strong recommendations, can be found here.
Dr. Kirkpatrick also noted that the conference included a symposium on bile acids featuring three cholestatic liver disease experts. He particularly highlighted Dr. Binita Kamath’s talk about the work being conducted around ileal bile acid transporter (IBAT) disruption. IBATs are molecules involved in the reabsorption of bile acids from the intestine, and novel drugs targeting IBATs show promise for treating the itch associated with liver disease. “It sounds like relief is coming for PSC patients with pruritus,” he said.
A poster about a multinational pruritus study in which PSC Partners participated was presented at the ILC by Dr. Kris Kowdley of Washington State University. PSC Partners CEO Ricky Safer, Registry Director Rachel Gomel, and Medical Liaison Joanne Hatchett are among the co-authors.
You can find a link to the poster abstract on the Registry’s new “Publications Related to Clinical Trials” page, which is accessible to both Registry participants and other patients with PSC interested in joining clinical trials. Look under the Mirum trial heading for the link to the 2022 Kowdley article in the Journal of Hepatology .
The 6th Biennial Meeting of the International PSC Study Group (IPSCSG) also took place at the 2022 ILC. The IPSCSG’s aim is to coordinate PSC research projects between leading institutions worldwide. Jesse Kirkpatrick is a member of the IPSCSG, as is Ruth-Anne Pai of PSC Partners. Dr. Kirkpatrick is an integral part of PSC Partners’ efforts to expand its global reach through the International Collaborative Research Network initiative and informational webinars featuring international research and advocacy partners.
*The American Association for the Study of Liver Diseases (AASLD) has also recently published a PSC Guidance, which can be found here.
PLEASE NOTE: While meetings such as the recent EASL ILC are for scientists, professional organizations are increasingly becoming more accessible for patients. If you are interested in following EASL and accessing its scientific publications and online resources, EASL has announced a new patient membership option at a cost of €25 (Euros, about $24 US). Visit their membership page for more information.
If you are interested in attending scientific meetings, the AASLD is hosting The Liver Meeting® in Washington, DC, November 4-8, 2022, and registration for patients/caregivers is available for both in-person and virtual attendance at a very reduced rate of $50. Most of the content is aimed at researchers and clinicians, but there is a patient/caregiver track as well. The sessions cover all things liver-related; cholestatic liver disease is a small part of the agenda. Register here.
Meet Director of Research Strategy Ruth-Anne Pai, PhD
When doctoral candidate Ruth-Anne Pai was matched with PSC Partners as a scientific advisor through the Chan Zuckerberg Initiative’s Rare As One (RAO) project, little did she know that she had found her next professional home. After advising the organization for a few months, Ruth-Anne discovered that PSC Partners was planning to hire a director of research strategy.
“The role aligned so well with what I hoped to do after my PhD [studies] and I was thrilled when offered the opportunity to position my scientific training to support the PSC community,” Ruth-Anne said. She joined the PSC Partners staff in April 2021.
A native of eastern Pennsylvania, Ruth-Anne earned a BA in Biological Sciences at Cornell University and a PhD in Immunology from the University of Pennsylvania. Her doctoral dissertation included identification of two new treatments for an idiopathic form of Castleman disease – another rare disease with liver involvement.
Her mentor at UPenn, Dr. David Fajgenbaum – himself a Castleman patient – was the keynote speaker at the 2022 PSC Partners annual conference. “I’ve had the amazing honor of working with Ruth-Anne Langan Pai over the years on Castleman’s Disease,” he said in his conference address, “and I’m just so thrilled that she is the research director for PSC Partners doing such important work.”
Ruth-Anne’s focus at PSC Partners is on several new initiatives. She has a leadership role in crafting a Strategic Research Plan and launching the International Collaborative Research Network (ICRNetwork); and she is integrally involved developing the Worldwide Integration of Natural History Databases (WIND) project and a new PSC-specific patient-reported outcome measure (PROM).
“Having Ruth-Anne Pai among us has been a game changer!” said Registry Director Rachel Gomel. “She has led the PSC Partners leadership team to embark in patient-driven research and has helped us bring the patient voice to the forefront."
Ruth-Anne’s dedication to research was inspired by her ninth-grade biology teacher, who instilled in her “a love for scientific exploration through science fair.” Ruth-Anne developed a specific interest in immunology at Cornell, where she decided to focus on human disease.
As a new PhD student at UPenn, Ruth-Anne was offered a lab rotation opportunity working with Dr. Fajgenbaum on Castleman disease research. “Dr. David Fajgenbaum taught me to always remember the needs of the patient community I serve and to work with urgency and purpose every day,” she said.
When asked what insights into PSC her background in immunology provides, she replied, “There are many parallels between the work and skills I gained during my PhD [studies], and the research landscape in PSC, from the challenges of studying a heterogeneous rare disease to the importance of utilizing a multiomic approach to study early disease mechanisms.”
“At PSC Partners, my ultimate goal is to provide all of the support I possibly can to accelerate the discovery and development of treatments and a cure for PSC,” said Ruth-Anne. “While one aspect of this is to develop key research projects and collaborations, I aim to support the PSC community in any way that leads to improved quality of life and outcomes.”
Ruth-Anne Pai presented a poster illustrating PSC Partners' Roadmap Initiative at the CZI Rare As One meeting in June 2022.
As a researcher, Ruth-Anne understands the significance of the PSC Partners Registry. “Participation from the patient and caregiver community is so critical in that it enables the completion of clinical studies and is an incredible resource for PSC researchers,” she said. “We are so grateful to current and future participants in the Registry, who are active and crucial contributors to our quest for a cure for PSC.”
Ruth-Anne presently lives near Seattle, Washington, with her husband, where they enjoy trail-hiking and traveling to visit family.
Don't forget to check the Registry Clinical Trials page for updates on active clinical trials!
Click image or here to visit the Registry list of PSC ongoing clinical trials.
“Together, we are creating a world where a PSC diagnosis comes with a cure!”
Established in collaboration with the Office of Rare Diseases Research (ORDR), the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH)
© 2022 PSC Partners Seeking a Cure