Monthly Webinar Series May 2019 Todays Agenda Announcements & - PowerPoint PPT Presentation

Monthly Webinar Series May 2019

Today’s Agenda Announcements & Trial Updates Sandi Cassard Recent Enrollments Christina Grabarits Rowing Competition & Top Enroller Christina Grabarits Scott Newsome Protocol Refresher and Ellen Mowry Q&A All

Announcements & Trial Updates SANDI CASSARD

Study Updates – Enrollment THANK YOU to activated sites for continuing to screen and enroll patients! We have 43 sites activated and 167 patients enrolled as of 4/30/19! Please try to find at least 1 new candidate each week so we can accelerate enrollment!!! ______________________________________________________________________________

Study Updates - Reminders 1) When consenting patients for the trial, please document the consent process, as detailed in the protocol and MOP, and upload signed consent form and completed DOC process form to VISION database under Source Docs tab, item # 10. 2) PLEASE ENTER VISIT DATA WITHIN 1 WEEK OF THE VISIT AND UPLOAD PDFs of SOURCE DATA SO WE CAN MONITOR THE DATA! We need all visit CRFs to verify the data. CRFs may be scanned as a single PDF, if preferred, and uploaded under Source Docs tab, item # 9.

Study Updates – Revised CRFs 3) Please see study website (http://treat-mstrial.org – Documents section) for most up-to-date case report forms (CRFs), including version 2.0 for baseline and month 6 visits. Month 12 visit CRFs are also posted. ◦ Month 6 Relapse Assessment CRF recently updated to capture data from review of MRI performed after 6 months on DMT.

Study Updates – Revised CRFs

Study Updates – VISION Database - EDSS 4) Please ensure EDSS examiners use our study’s EDSS CRFs and NOT the neurostatus form. ◦ Recent updates in VISION database include fixing the order of entering the Ataxia questions under cerebellar functional system. VISION database now matches CRFs.

Study Updates – Baseline MRIs 5) Please make sure to upload the baseline MRI used to risk stratify the patient. You may need to request CD from patient or ask patient to bring it in at next visit/mail it to you. See MRI manual – version 6.0 on the study website for instructions.

Announcements Email sent to sites Impact of Mt with link to a brief Reminder email Everest Survey 3-5 minute survey coming soon! due! on 4/16.

Recent Enrollments CHRISTINA GRABARITS

The Rowing Competition CHRISTINA GRABARITS

Rowing Competition Standings 1- Team E (44 points) 2- Team A (36 points) 2- Team F (36 points) 3- Team D (34 points) 4- Team H (26 points) 5- Team B (24 points) 6- Team C (22 points) 7- Team G (18 points)

Rowing Competition Standings Site Points 1. Norton Neurology 124 2. UAB 109 Individual Site 3. UFL Gainesville 86 4. Christiana Care 71 Competition 5. Swedish 70 6. Advanced Neuro Spc 67 7. U Kansas Med Ctr 65 8. NYU 61 9. U Washington 54 10. Mayo Clinic 50

Rowing Competition https://treat.preludedynamics.com

Monthly Randomization Race April’s Top Performers: Site Randomizations Geisinger Clinic 2 KU Medical Center Research Institute 2 Norton Neurology Services 2 University of Alabama at Birmingham 2 Johns Hopkins Hospital 6

April’s Top Enroller: Norton Neurology Services $50

TR TRaditional vs. Early Aggressive Therapy for Multiple Sclerosis (TREAT-MS) Trial ELLEN M. MOWRY, M.D., M.C.R. SCOTT D. NEWSOME, D.O. ASSOCIAT ATE PROFESSOR OF ASSOCIATE PROFESSOR OF NEUROLOGY AND EPIDEMIOLOGY NEUROLOGY JOHNS HOPKINS UNIVERSITY JOHNS HOPKINS UNIVERSITY

Overview/Reminder of Rationale for TREAT-MS MS • There is is a great unmet need to id identify fy th the most appropriate tr treatment str trategy for pe people wit ith MS, , espe pecially early in in th the dis disease course • Whe hether a more aggressive tr treatment str trategy early in in MS pr prevents lo longer- term dis isability is is not cle clear. . • Th Ther ere may be be sub subgroups of of pa patie ients who ho wou ould ld be benefit it mor ore e tha than ot othe hers • Rece cently pu published observ rvational stu tudies hi hint towards early aggressive th therapy min inimizing dis isability and conversion to secondary progressive MS vs. . tr traditional.

TREAT-MS: Objectives 1 . To evaluate whether an “early aggressive” therapy approach, versus starting wit ith a tr traditional th therapy, , in influences th the in intermediate-term ris isk of f dis disability pr progression. => => Will ill in investigate overall ll an and with ithin in str trata of of people at t hig igher versu sus lo lower risk risk of of lon longer-term dis isab abili ility 2. 2. To evaluate if if, , among patients deemed at t lo lower ris isk for dis isability acc ccumulation who start on tr traditional, , fir first-line MS th therapies but experience br breakthrough dis disease, , th those who ho swit itch to a hig higher-efficacy th therapy versus a ne new fir first-line th therapy have dif ifferent in intermediate-term ris isk of f dis isability acc ccumulation.

TREAT-MS: Study Design Overview: Pragmatic ic tria trial l enrolli lling 90 900 0 par articip ipants who meet 20 2017 17 cri criteria for rela lapsin ing- remittin ing MS Si Sites: ~5 ~50 0 si sites ac across ss th the Unit ited St States (ac (academic ic an and priv rivate neurology practices) In Interv rventions: Hig igher-efficacy versus tr traditional l th therapies Prim rimary ry Outcome: Di Disabili ility progression (E (EDSS-plu lus [r [rater-blin linded]) Par articipant Du Duration: Up to o 54 54 months EDSS=Expanded Disability Status Scale plus=Timed 25-foot walk and nine hole peg test

Eligibility Criteria Inclusion Criteria Exclusion Criteria Age 18-60 Prior use of rituximab, ocrelizumab, alemtuzumab, mitoxantrone or cladribine Meets 2017 McDonald criteria for relapsing-remitting MS Use of any MS DMT for > 6 months^ or use of any MS DMT within past 6 months; treatment with teriflunomide within past 2 years unless rapid wash out done Must be EITHER JC virus Ab negative or low positive (index Prior treatment with experimental aggressive therapies, antibody titer <0.9), OR negative for: Hepatitis B* and C*, other investigational immunomodulatory/suppressive TB** medication HIV negative Pregnant or breastfeeding Women of child-bearing age who are planning or strongly If patient has prior history of chemotherapy*** or considering conception during the study time frame malignancy, documentation in chart explaining why potential risks of higher-efficacy therapy are justified *Patients who demonstrate satisfactory use of antivirals for Hepatitis B or who successfully completed treatment for Hepatitis C may be enrolled, if approved by a gastroenterologist; **Patients with past history of appropriately-treated TB (latent or active) are eligible; **None in past year; ^ If on DMT for ≤6 months, reason for discontinuation must not have been breakthrough disease

Risk Strata Determinants Enrollment within 6 months of 1 st attack: high risk if both Clinical or radiographic involvement of the spinal cord OR brainstem/cerebellum AND BRAIN MRI with >10 T2 lesions OR ≥4 Gadolinium -positive (Gad+) lesions, OR another attack in the first 6 months since the 1 st attack, OR new lesions on MRI if a subsequent MRI is available already Enrollment > 6 months since 1 st attack: high risk if any 2 of the 4 are true Clinical or radiographic involvement of the spinal cord OR brainstem/cerebellum BRAIN MRI with >10 T2 lesions OR ≥4 Gad+ lesions Residual damage (incomplete recovery based on exam [Functional System Score ≥2 , with the deficit(s) on exam corresponding to the region of prior relapse that began > 6 months ago]) Ongoing activity in the past year: 2 or more relapses OR ≥3 new MRI lesions in past year OR ≥2 Gad+ lesions

Original Randomization 1:1 randomization 1:1 randomization

Medication Classes Traditional (First-line) Early Aggressive Glatiramer acetate (Copaxone, Glatopa, other generics) Alemtuzumab (Lemtrada) Intramuscular interferon (Avonex) Ocrelizumab (Ocrevus) Subcutaneous interferon (Betaseron, Extavia, Rebif) Rituximab (Rituxan) Natalizumab (Tysabri) Pegylated interferon (Plegridy) Cladribine (Mavenclad)* Teriflunomide (Aubagio) Dimethyl fumarate (Tecfidera) Fingolimod (Gilenya) *New; classification based on consensus-based approach by Siponimod (Mayzent)* Study Advisory Committee (IRB approval pending)

Switch in Therapy for Breakthrough? High risk disability indicators Low risk disability indicators