Mo Monthly y Webinar r Se Seri ries October, 2018 Todays - - PowerPoint PPT Presentation

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

Giovannoni G et al. N Engl J Med 2010;362:416-426.; Giovannoni G. Neurotherapeutics 2017; 14;874-887

*analogue of deoxyadenosine that is partially resistant to adenosine deaminase-> high levels of cladribine inhibit DNA synthesis resulting in lymphocyte depletion

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

• ss S

Subgr grou

• ups

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

*Not fit to scale

104.9 102.3

• 11. University of California at San Francisco

89.4

• 2. Central Texas Neurology Consultants

46.7 62.9 121.9 85.9

• 13. Columbia Presbyterian
• 4. Dignity Health Sacramento
• 6. Massachusetts General Hospital

44.0

• 3. Advanced Neurology Specialists

86.3

• 5. Cedars Sinai
• 8. Vanderbilt University Medical Center
• 7. University of Washington
• 9. Providence Health

42.7

• 1. Baylor Scott & White Health
• 8. Norton Neurology Specialists
• 2. Christiana Care
• 5. NYU School of Medicine
• 10. University of Rochester

Activated Sites

• 7. Swedish Medical Center
• 4. University of Vermont
• 9. University of Alabama at Birmingham
• 6. University of Florida Gainesville
• 12. University of Kansas Medical Center
• 3. University of Cincinnati
• 10. Neurology Specialists of Tidewater
• 1. Johns Hopkins University

Month 3 Month 2 Month 1

• 14. Mayo Clinic

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

Mount Everest Standings

• Mt. Everest on GEMS

Clarifications for Case Report Forms

SCOTT NEWSOME & MADIHA QUTAB

Cl Clari rification

• n of
• f 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)

• r remote (>90 days)

Follow up visits- paper CRFs should be brought to clinic to assess whether new or

• ngoing 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

• ms

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

• mization
• n Error
• rs and Missing Data
• Recommend treating clinician hold onto paperwork until done

(specifically pre-randomization CRFs) to prevent risk classificationàrandomization errors

• Strongly encourage doing baseline PROs at visits, when applicable

Ba Baseline: MRI MRI log

• gistics
• 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

• gistics: t

: timi ming of

• f 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

• banking 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

Breakdown of Teams

Sites are broken up into regional teams Regions are further split up into different teams (Team A, Team B, etc.)

There will be a competition between the different teams, as well as a ranking of the top 10 performing sites in the trial

West Midwest South Northeast Team A Team B Team C Team D Team E Team F Team G

Advanced Neurology Specialists University of California at San Francisco University of Kansas Medical Center Norton Neurology Services Christiana Care New York University School of Medicine University of Vermont Swedish Medical Center Cedars Sinai Mayo Clinic University of Florida Gainesville University of Alabama at Birmingham University of Rochester Massachusetts General Hospital University of Washington University of California Los Angeles Rush University Medical Center University of Louisville Multiple Sclerosis Center

• f Atlanta

Stony Brook University University of Massachusetts Worcester Providence Health University of California San Diego University of Michigan Central Texas Neurology Consultants Neurology Specialists of Tidewater Hackensack University Medical Center Columbia Presbyterian Billings Clinic Barrow Neurological Institute Wayne State University Vanderbilt University Medical Center Georgetown University Icahn School of Medicine Geisinger Clinic University of Utah Dignity Health Sacramento MDH Research LLC University of South Florida Health University of Maryland Holy Name MD Center Allegheny Health Network Ohio Health Baylor Scott & White Health Barnabas Multiple Sclerosis Comp. Care Center Oklahoma Medical Research Foundation University of Cincinnati

Sne Sneak Pe Peek of the he teams ms

Team D Points Site Site Site Site Team E Points Site Site Site Site Team F Points Site Site Site Site Team C Points Site Site Site Site Team G Points Site Site Site Site Team A Points Site Site Site Site Team B Points Site Site Site Site

Rowin Rowing g Comp

• mpetition

etition Standi Standings tem ngs template plate

Site Points

1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

JHU Points

Me Metr tric ics

• Webinars
• Screened
• Randomized
• % Data entered within 2

weeks

• % Queries answered

within 2 weeks

Ongoing Variables

• Visits completed
• M6
• M12
• M18
• M24
• M30
• M36
• M42
• M48

In-person Visits

• ePRO completed within

time period

• Baseline
• M3
• M9
• M21
• M33
• M45
• M48
• EOT

ePROS Primary Outcome Assessments

• EDSS
• 25-Foot Walk Test
• 9-Hole Peg Test

Keep eep in in Min Mind… d…

• All points will be awarded from the date of each site’s

activation

• In order to calculate the team total, we will take the

average of all activated site points

• The competition will restart each year

Open for Questions

Webinar Survey

Thank you for taking our webinar survey!

The webinar dates will remain as the first Wednesday and first Thursday of every month

Thank You for attending today’s webinar!

Encore Performance: Tomorrow 9am

November’s Monthly Webinar will be held on the 7th at 3pm and 8th at 9am Eastern