Mo Monthly y Webinar r Se Seri ries October, 2018
Today’s Agenda • Announcements/Trial Updates Scott Newsome • Cladribine: Results of the SAC vote Scott Newsome • Study Updates • Mt. Everest Christina Grabarits • Clarifications for Case Report Forms Scott Newsome & Madiha Qutab • Rowing Competition Christina Grabarits • Q & A Team
Announcements/Trial Updates SCOTT NEWSOME
Study Updates: Enrollment THANK YOU to activated sites for beginning to screen and enroll patients! We now have 27 patients enrolled, including: Christiana Care = 2 patients Advanced Neurology Specialists = 4 patients University of Florida = 3 patients Norton Neurology Services = 1 patient Swedish Medical Center = 1 patient UAB = 1 patient ______________________________________________________________________________
Coming Around the Bend: 4 sites will be IRB approved this week. Additional sites are being submitted to the IRB this week for approval. Thank you to all sites for completing start-up activities and working towards site activation!
Next SAC Meeting SAC members: hold the afternoon of February 27, 2019 for a meeting in Dallas (afternoon prior to ACTRIMS)
Activated Sites
Cladribine: Results of the SAC Vote (trial slides courtesy of Dr. Gabriel Pardo) SCOTT NEWSOME
Cladribine * Clinical Trial Program • CLARITY, CLARITY EXT, ORACLE-MS, ONWARD, PREMIERE registry • ~10,000 patient-years • Up to 8 years follow-up • 3.5mg/kg dosing over two years (10 days/year) • Adaptive immune system • Approved outside US and resubmission to FDA *analogue of deoxyadenosine that is partially resistant to adenosine deaminase-> high levels of cladribine inhibit DNA synthesis resulting in lymphocyte depletion Giovannoni G et al. N Engl J Med 2010;362:416-426.; Giovannoni G. Neurotherapeutics 2017; 14;874-887
CLARITY Study • Phase III study to evaluate effect of short-course, oral cladribine versus placebo in patients with relapsing-remitting MS over 96 weeks (N=1326) • EDSS 0-5.5 at baseline • No more than 1 prior failed DMD treatment course • Randomized treatment groups: • 5.25 mg/kg (n=456) • 3.5 mg/kg (n=433) • Placebo (n=437) • Course of treatment: 4 or 5 consecutive days/month • 2 or 4 consecutive months for year 1 (low- or high-dose group, respectively) • 2 consecutive months in year 2 Giovannoni G, et al. N Engl J Med. 2010;362:416-426.
CLARITY trial design
ARR –primary endpoint
CL CLAR ARITY TY: Be Benefi fits Ac Acros oss S Subgr grou oups Reductions in MRI parameters • Significant reductions in T1 Gd+, T2, and CU lesions/patient/scan over 96 weeks – Patients with <1, 2, ≥3 relapses in the 12 months prior to study – Patients with varying disease duration (<3, 3-10, >10 years) and EDSS • Similar findings also observed for patients regardless of age, gender, prior treatment status, disability status, presence of Gd+ lesions at baseline, and baseline T2 lesion burden Comi G, et al. Presented at: 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis; October 13-16, 2010; Gothenburg, Sweden. P403
SAC Vote: Cladribine Classification
The Mount Everest Climb CHRISTINA GRABARITS
Activation! The Summit End of Month 3 Lhotse Wall End of Month 2 Icy Lhotse Wall End of Month 1 Valley of Silence Receipt of Protocol and Contract Base Camp
ELEVATION Mount Everest Contenders Activated Sites 1. Johns Hopkins University Month 3 2. Christiana Care 3. Advanced Neurology Specialists Month 2 4. University of Vermont 1. Baylor Scott & White Health 121.9 5. NYU School of Medicine Month 1 6. University of Florida Gainesville 104.9 2. Central Texas Neurology Consultants 7. Swedish Medical Center 8. Norton Neurology Specialists 102.3 3. University of Cincinnati 9. University of Alabama at Birmingham 10. University of Rochester 89.4 4. Dignity Health Sacramento 11. University of California at San Francisco 12. University of Kansas Medical Center 86.3 5. Cedars Sinai 13. Columbia Presbyterian 14. Mayo Clinic 85.9 6. Massachusetts General Hospital 62.9 7. University of Washington 46.7 8. Vanderbilt University Medical Center 44.0 9. Providence Health 10. Neurology Specialists of Tidewater 42.7 *Not fit to scale
Mount Everest Standings Rank Activated Sites Final Points 1 Christiana Care 133.5 2 Norton Neurology Specialists 129.9 3 Columbia Presbyterian 111.6 4 Advanced Neurology Specialists 84.3 5 New York University School of Medicine 84.2 6 University of Rochester 49.5 7 Swedish Medical Center 46.5 8 University of Vermont 38.8 9 University of Alabama at Birmingham 38.1 10 University of Florida Gainesville 31.0
Mt. Everest on GEMS
Clarifications for Case Report Forms SCOTT NEWSOME & MADIHA QUTAB
Cl Clari rification on of of CRF CRFs: C : Charact cteri rizi zing R Risk a at Ba Baseline • Determining precise true “onset” of symptoms can be tough (> or < 6 months disease duration); Do your best educated guess as one would do in clinical practice, and document rationale. • Clearing up some MRI criteria “gray areas” (disability risk, new lesions over time): 1) >10 T2 lesions (brain) 2) lesion size and location (discussed size criteria but difficult to standardize based on literature and in a pragmatic trial; use your best judgment- if you think a lesion is demyelinating in nature-> it counts
CRF CRFs: Symptoms and nd Conc ncomitant t Med/ ed/Ther Therapi pies es • Recording MS Signs and Symptoms Baseline visit - 1) present or not, 2) if they have, was the onset recent (within 90 days) or remote (>90 days) Follow up visits - paper CRFs should be brought to clinic to assess whether new or ongoing S&S exist • Recording Concomitant Meds/Therapies: Only those associated with MS Signs and Symptoms, recommended by a health care provider Þ Yes- started Provigil for fatigue Þ No- patient decided to start gingko biloba for cognitive issues, on their own Þ Yes- patient started L-Carnitine for fatigue at the recommendation of treating clinician Þ No- patient was started on vitamin D for their MS Þ Yes- treating clinician/team recommended PT and Acupuncture for pain and mobility (therapies need to be recorded separately)
CRF CRFs: MS MS Si Signs and Symp mptoms oms Enter Date first reported (visit date) next to each symptom that is new or worsening
CRF CRFs at Ba Baseline: Preventing Ri Risk & Ra Random omization on Error ors and Missing Data • Recommend treating clinician hold onto paperwork until done (specifically pre-randomization CRFs) to prevent risk classification à randomization errors • Strongly encourage doing baseline PROs at visits, when applicable
Ba Baseline: MRI MRI log ogistics • Repeat initial baseline MRI especially if quality poor or when done at an outside radiology center- based on CMSC MRI guidelines (understand that this may not be possible in all cases; co- pay/financial issues, insurance denial, etc.) • RadNet connection, and plans for expansion beyond
MR MRI l log ogistics: t : timi ming of of mon month 6 MR 6 MRI • Perhaps the most critical MRI in terms of having it, and its timing. Why? • Able to switch therapy for ANY NEW breakthrough disease occurring AFTER 6 months on therapy • Doing the month 6 MRI at the wrong time can reduce the ability to use it to support claim for breakthrough disease: If “month 6” MRI done: ≤ 6 months: for the subsequent MRI scan, we will only be able to confirm a new lesion occurred “after 6 months on therapy” if the new lesion is enhancing >6 months-8 months: can serve as true reference MRI scan against which subsequent new lesions can be confirmed as occurring “after 6 months on therapy” >8 months: if a new lesion is present AND enhancing, we can assume it developed “after 6 months on therapy;” if not enhancing, the MRI will simply be a reference MRI scan against which subsequent new lesions can be confirmed • Advice: unless you are controlling the scheduling of the “month 6 MRI”, don’t order it until AFTER they have been on the therapy for 6 months. • If you prefer to have MRI in hand at the visit, since clinic visit windows are wide, perhaps schedule MRI plus clinic visit for a bit >6 months AFTER start date of DMT
Biobanking Update SUSAN EMRICH
Bi Biob obanking Up Update • Protocol version 1.8 and Consent form version 1.2 that include the biobanking substudy have been approved by Johns Hopkins central IRB. • Consent forms will be revised for all sites and if sites are participating in the biobanking substudy, patients will be able to opt in or out of the substudy. • Johns Hopkins will provide the supplies for drawing blood and shipping. The majority of tubes collected will be shipped ambient the same day, without any processing. Sites will be asked to spin tubes for serum aliquots and freeze them locally, batch shipping these on dry ice at a later time. • To date Johns Hopkins as well as Advanced Neurology Specialists and University of Alabama at Birmingham have enrolled patients in the substudy.
The Rowing Competition CHRISTINA GRABARITS
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