Monthly Webinar Series January 2020 Todays Agenda Announcements - - PowerPoint PPT Presentation

Monthly Webinar Series

January 2020

Today’s Agenda

Announcements & Trial Updates/Reminders Sandi Cassard Breakthrough Disease and DMT Change - Refresher Ellen Mowry, Scott Newsome Monthly Randomization Race Daniel Amirault Q&A All

Announcements & Trial Updates

Enrollment News

As of Tuesday, January 7th, we have enrolled 414 patients toward

• ur goal of 900!

We are rapidly approaching the half-way mark, and we are grateful for your partnership. WE’VE GOT THIS, as a team. Please continue to screen and enroll patients while we work on a contract extension with PCORI. Please try to find at least 1 new candidate each week so we can accelerate enrollment!!!

Weekly Enrollment Trackers

• Graphical representations of the # enrolled versus the # YOU PLEDGED TO ENROLL
• Have been modified to meet our new target enrollment completion of 6/2020

Example of site on track:

5 10 15 20 25

TREAT-MS Trial UAB

Enrollment Commitment Current Enrollment

Example of sites that need to ramp up:

5 10 15 20 25

TREAT-MS Trial Site B

Enrollment Commitment Current Enrollment 5 10 15 20 25 July-18 August-18 September-18 October-18 November-18 December-18 January-19 February-19 March-19 April-19 May-19 June-19 July-19 August-19 September-19 October-19 November-19 December-19 January-20 February-20 March-20 April-20 May-20 June-20

TREAT-MS Trial Site A

Enrollment Commitment Current Enrollment

Enrollment Considerations If You Are Behind: Major Blockages

• Your center is not seeing enough newly-diagnosed, untreated patients
• Solutions: you may need to reach out to referring clinicians at your institution or in the community, speak at Grand Rounds, engage

your patient-partner

• You may not be catching people “in time”– consider that you may need to open up some “priority” slots with site PI for newly-

referred patients to the center and see those patients quickly, before referring physicians begin therapy

• Your colleagues don’t refer to the trial
• You may need to re-explain the equipoise of the study, the high degree of physician-patient autonomy, and the flexibility (and even

urging) of treatment switches for breakthrough disease

• You may need to ensure the site PI is seeing potentially eligible patients
• Your patients don’t seem interested/already have a treatment in mind
• You likely need to spend more time with the patient (ensure at least 2 visits, bring up the trial at visit #1)
• Usually best for the physician/clinician to explain trial and go over consent form
• You may need to check your own explanation of equipoise

REMEMBER…. THERE ARE PLENTY OF SITES THAT HAVE REACHED AND ARE NOW PURSUING HIGHER TARGETS. THESE GOALS ARE READILY ACCOMPLISHABLE. YOU MADE THE PLEDGE TO DO IT…. SO PLEASE COMMIT TO FIGURING OUT YOUR BLOCKAGES AND MOVING PAST THEM! REACH OUT TO THE SITE PIS OR TO OTHERS WHO ARE SUCCEEDING TO GET TIPS!

Upcoming Important Dates

• January 10, 2020 – You will receive continuing review materials

from the Johns Hopkins Coordinating Center (JHCC) to review / edit – make sure VISION is up-to-date NOW!!!

• January 17, 2020 – Continuing review materials due back to JHCC
• January 24, 2020 – Target date for submission of all sites to central

IRB for continuing review

• January 31, 2020 – DSMB meeting
• February 26, 2020 – SAC Meeting – West Palm Beach, Florida

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.

Consent documentation

Study Updates - Reminders

3) Please visit study website (http://treat-mstrial.org – Documents section) for most up-to-date case report forms (CRFs). 4) Please share webinar slides with study team members that are unable to attend live presentations. 5) Reach out to the coordinating center if you have a patient that wants to withdraw or is having trouble getting started on DMT. 6) Promptly report any SAE (e.g., unplanned hospitalization) in VISION so we can inform our medical monitor and the IRB!

Breakthrough Disease and DMT Change

ELLEN MOWRY & SCOTT NEWSOME

Original Randomization

1:1 randomization 1:1 randomization

Who Gets Re-randomized for Breakthrough?

High risk disability indicators Low risk disability indicators

Switch in Therapy for Breakthrough?

High risk disability indicators Low risk disability indicators

• The other patients do not have a re-randomization for first

breakthrough if they are changing therapy

• If patients in the re-randomized group have a second breakthrough

after 6 months on THAT therapy, there is no more randomization

Defining Breakthrough Disease

• ANY breakthrough disease after 6 months on therapy will make

allowable a discussion about change in therapy

• Gadolinium-enhancing lesions can be used as evidence of

breakthrough disease activity if the “month 6” first on treatment MRI is performed after 7 months on therapy

• Treating clinicians required to document discussion of switching

therapy if excessive breakthrough has occurred

• Excessive breakthrough= >1 new lesion, or any relapse, after the

time periods noted above

“Month 6” MRI – Timing and Interpretation

Doing the “month 6” MRI too early can reduce the ability to use it to support a claim for breakthrough disease. If the “month 6” MRI is completed: < 6 months after starting on therapy: For the subsequent MRI scan (month 12 MRI), treating clinician will only be able to confirm a new lesion occurred “after 6 months on therapy” if the new lesion is enhancing. > 6 months to 7 months after starting on therapy: Scan can serve as a true reference MRI scan against which subsequent new lesions can be counted as occurring “after 6 months on therapy.” > 7 months after starting on therapy: If a new lesion is present AND enhancing, treating clinician 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.

Scheduling logistics for MRIs: Examples

Question: What is the window for getting the Month 6 MRI completed? How about the Month 12 MRI? Answer: The Month 6 MRI should be completed after the patient has been on his/her 1st DMT for AT LEAST 6

• months. For setting up your visit tracker and optimal timing of the Month 6 MRI, see below example:

Example 1: DMT started within 2 months of randomization Randomization date: 02/15/19 DMT start date: 03/25/19 Month 6 MRI: after 09/25/19, assuming patient has remained on the same DMT for 6 months Month 6 MRI if you suspect new activity and want to use it as evidence of breakthrough disease: after 10/25/19. Month 12 MRI: based on randomization date. Visit window is wide (9 months after randomization up to 18 months after randomization – between 11/15/19 and 8/15/20). Please order it when it is clinically indicated.

Scheduling logistics for MRIs: Examples

Question: What is the window for getting the Month 6 MRI completed? How about the Month 12 MRI? Answer: The Month 6 MRI should be completed after the patient has been on his/her 1st DMT for AT LEAST 6

• months. For setting up your visit tracker and optimal timing of the Month 6 MRI, see below example:

Example 2: Delay in start date for DMT Randomization date: 02/15/19 DMT start date: 5/12/19 Month 6 MRI: after 11/12/19, assuming patient has remained on the same DMT for 6 months Month 6 MRI if you suspect new activity and want to use it as evidence of breakthrough disease: after 12/12/19. You may still label and upload this as a Month 6 MRI, even if it falls within the early part of the Month 12 MRI visit window. Month 12 MRI: Visit window is wide (9 months after randomization up to 18 months after randomization – between 11/15/19 and 8/15/20). Please order it when it is clinically indicated.

Early DMT Changed – MRI timing

Question: Our patient took her 1st DMT for 2 months, then discontinued due to side effects. She is starting her next DMT within the same treatment class within a month of discontinuing the 1st

• medication. When should we obtain her month 6 MRI? How about her month 12 MRI?

Answer: This patient can be re-baselined prior to starting the 2nd DMT, and then the month 6 MRI will be after the patient has been on this 2nd DMT for at least 6 months. The re-baseline can be uploaded in the month 6 MRI slot and the MRI after 6 months on the 2nd DMT can be uploaded as a month 12 MRI. Example: Baseline MRI: 12/15/18 Next MRI: 06/15/19 (upload as month 6 MRI) Randomization date: 2/15/19 2nd DMT start date: 6/20/19 1st DMT start date: 3/25/19 Next MRI: 01/25/20 (upload as month 12 MRI) 1st DMT stop date: 5/25/19

Other Important Reminders

• Treatment discontinuation for other reasons: Participants who discontinue therapies for

reasons other than breakthrough disease (e.g. intolerance, adverse effect, desire to conceive) will be encouraged (except in the instance of trying to conceive or pregnancy itself, or when such treatment is otherwise contraindicated) to choose another therapy within the efficacy class to which the discontinued therapy belongs.

• The factors that supported each individual treatment choice will be documented at

baseline and at any point a switch is made.

• Safety reporting: collating all the AEs experienced by participants for each MS-specific

disease-modifying therapies is out of the scope of this trial.

• Capture all SAEs and any AE that leads to a DMT dose change or discontinuation.

Eligibility Criteria: Clarifying infection screening

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 antibody titer <0.9), OR negative for: Hepatitis B* and C*, TB** Prior treatment with experimental aggressive therapies,

• ther investigational immunomodulatory/suppressive

medication HIV negative Pregnant or breastfeeding If patient has prior history of chemotherapy*** or malignancy, documentation in chart explaining why potential risks of higher-efficacy therapy are justified Women of child-bearing age who are planning or strongly considering conception during the study time frame

*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

Voting Results: New Medications

Traditional (First-line) Glatiramer acetate (Copaxone, Glatopa, other generics) Intramuscular interferon (Avonex) Subcutaneous interferon (Betaseron, Extavia, Rebif) Pegylated interferon (Plegridy) Teriflunomide (Aubagio) Dimethyl fumarate (Tecfidera)/Diroximel fumarate (Vumerity*) Fingolimod (Gilenya and generics*) Siponimod (Mayzent) Early Aggressive Alemtuzumab (Lemtrada) Ocrelizumab (Ocrevus) Rituximab (Rituxan) Natalizumab (Tysabri) Cladribine (Mavenclad)

*Vumerity, generic fingolimod pending IRB change in research

Monthly Randomization Race

DANIEL AMIRAULT

Monthly Randomization Race

December’s Top Performers:

Site # of Randomizations Johns Hopkins Hospital 7 University of Utah 3

• St. Joseph’s Hospital and Medical Center Dignity Health

2

December’s Top Enroller:

University of Utah

$50

Open for Questions

Thank You for attending today’s webinar!

Encore tomorrow at 9:00 AM EST The February Monthly Webinar will be held on the 5th at 3 PM and 6th at 9 AM EST