In an article reporting the 18-month results of the Immune Tolerance Network’s (ITN) RAVE clinical trial, published August 1st in the New England Journal of Medicine, the ITN is providing unfettered access to the underlying clinical data and analysis code via the new clinical trials research portal, ITN TrialShare (itntrialshare.org). The data published today come from the ITN’s RAVE study led by John Stone, MD (Massachusetts General Hospital) and Ulrich Specks, MD (Mayo Clinic). The researchers demonstrated that a single course of rituximab therapy (anti-CD20; Rituxan, Genentech, Inc.) is as effective as the current standard of care regimen of drugs for remission induction and maintenance in patients with ANCA-associated Vasculitis (AAV). Rituximab has a shorter and simpler treatment course compared to standard therapy (cyclophosphamide), as well as an improved safety profile, thus offering significant treatment advancement for patients with AAV. This publication is the first to provide public access to the raw study data via direct links from the publication and its figures to the data sets in TrialShare. The accompanying editorial in NEJM highlights the utility of TrialShare in data sharing and transparency.
The FDA has announced that it intends to consider making de-identified and masked subject level data widely available to improve the efficiency and effectiveness of medical product development, recognizing that external experts should become actively engaged in the research. ITN TrialShare was created precisely to address this need, enabling researchers to share the results of the clinical trial data in an open and transparent manner, while protecting the privacy and anonymity of study participants by fully de-identifying the data. TrialShare gives researchers the ability to access raw study data, confirm published conclusions and interactively perform their own exploratory analyses using this data. TrialShare also provides access to the ITN specimen repository catalog, allowing users external to the trial to request specimens for follow-up experiments based on the data and available samples.
“TrialShare allows researchers from around the world to have direct access to ITN’s clinical trial data” said Gerald T. Nepom, MD, PhD, director of the ITN. “This will enhance scientific collaboration and greatly speed the sharing of the results of our studies.”
TrialShare is a significant advance in data sharing and transparency, allowing for collaborative hypothesis generation and specimen sharing between the ITN and the broader scientific community.
With the addition of the data from today’s publication, ITN TrialShare currently has data associated with six published manuscripts available to the public in the therapeutic areas of transplant, allergy, auto-immunity and diabetes. ITN will make the underlying data from all published studies, regardless of outcome, available through TrialShare. ITN TrialShare uses the open source LabKey server software. TrialShare can be accessed at ITNTrialShare.org.
RAVE Study 18-Month Results:
The RAVE study is a 197-patient randomized, double-blind, placebo-controlled trial comparing rituximab against cyclophosphamide for remission induction in patients with severe AAV. The FDA approved a label extension for rituximab for use in AAV after the initial 6-month results of the RAVE study demonstrated that rituximab in combination with glucocorticoids was non-inferior to cyclophosphamide in combination with glucocorticoids for inducing complete remission in patients with severe AAV (reported in the New England Journal of Medicine in 2010). This represented the first approved therapy for AAV in over 40 years.
Today's publication reports safety and relapse rates among the two treatment groups out to month 18. At 18 months, 39% of patients in the rituximab arm were relapse-free (n=39), compared to 33% in the standard therapy arm (n=32). There were no significant differences in overall adverse events between the two groups, although there were fewer cases of pneumonia and leukopenia in the rituximab arm.
These results suggest that a short course of rituximab (four once-weekly infusions) is as effective for the induction and maintenance of remission in severe AAV patients as continuous treatment over 18 months with standard immunosuppressive drugs that require ongoing monitoring for toxicities.
“The RAVE study is remarkable for several reasons,” said Ulrich Specks. “First, its results have provided patients who suffer from these chronically relapsing diseases with access to a very effective alternative to cyclophosphamide to induce remission. Second, the study has shown that a short course of 4 infusions of rituximab is as effective as 18 months of ongoing daily oral therapy with immunosuppressive drugs that require frequent blood test monitoring to assure their safe use. Third, the RAVE study is a model for successful partnerships of federal funding agencies, federally funded research organizations and industry for the study of rare diseases. Last not least, today’s publication illustrates how complete transparency between published study analyses and all raw study data can be provided to the public.”
Data sets and statistical analyses from the RAVE study are available to the public through ITN TrialShare, ITNTrialShare.org.