1. Phase 3 Uterine Fibroids M12-815 and M12-817 Monthly Site Telecon May 10 and 12, 2016

2. Housekeeping Please mute your line by pressing *6
To unmute your line, press #6
Please do not put the line on hold
Hold music disrupts the call
Instead, if you need to take the call, please hang up and dial back in
Questions can be asked via WebEx Chat feature or live at the end of the presentation
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

3. Attendance
Please document your attendance on your site training logs and by ing
The should be titled 815/817 Monthly Site Telecon Attendance and include:
Site Name/Site Number
A list of all individuals from your site in attendance at todays meeting and their role in the study (PI, Sub-I, Study Coordinator, etc.)
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

4. Study Status and Timelines
Agenda
Study Status and Timelines
Timing of Key Assessments Affecting Eligibility
Adverse Event Collection During Screening
Visit Window Calculator
Imaging Reminders
MRI Subset
Study Drug Reminders/Compliance
Vendor Support
Financial Disclosure Certification
Frequently Asked Questions
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

5. M12-815/M12-817 Timelines M12-815 M12-817 M12-816 (Extension)
First Subject Screened
December 2015
(Actual)
January 2016
-----
First Subject Randomized
March 2016
April 2016
September 2016
Last Subject Screened
January 2017
February 2017
Last Subject Randomized
April 2017
May 2017
November 2017
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

6. M12-815/M12-817 Study Status Activity M12-815 M12-817 Total
Number of Subjects Screened
295
274
569
Number of Subjects in Washout 18 15 33
Number of Screen Failed
110 95
205
Number of Subjects Active in Screening
165
163
328
Number of Subjects Randomized 2 1 3
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

7. M12-815/M12-817 Protocol Amendment
Upcoming Protocol Amendment:
M12-815
Protocol Amendment 2
M12-817
Protocol Amendment 1
Expected to be finalized by the end of May
Final Amendment and revised ICF to be sent to Schulman end of May/early June
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

8. Timing of Key Assessments Affecting Eligibility Margaret Kruelle

9. Screening Procedures
Although the Screening Period is approximately 2.5 to 3.5 months; time goes faster than you think!
Greater than 20 procedures/assessments that need to be performed
Some of which should be timed based on menstrual cycle
Every Site performs sequence of procedures differently
Every Subject may change the order or sequence of procedures
Recommend:
Least invasive PCV 1  Most Invasive PCV2  Randomization
Assess eligibility throughout the Screening Period
Once it’s been confirmed subject does not meet an inclusion/exclusion (including after any applicable repeat assessments/procedures confirm subject is not eligible), Subject should be screen-failed in IRT
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

10. Screening Algorithm for Scheduling Procedures
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

11. Timing of Screening Assessments
Determine if Subject is Initially Eligible
Subject signs/dates the informed consent form
Physical Exam, Vital Signs, Medical and Uterine Fibroid History, laboratory tests, etc.
TAU/TVU should be performed early in Screening (or Washout, if applicable) to confirm fibroid eligibility
If not performed at the same time as the TAU/TVU, the SIS should be performed as soon as the TAU/TVU report confirms fibroid eligibility
Dispense sanitary products and collection supplies and train on product collection
Perform Contraception Counseling and dispense contraceptives
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

12. Timing of Screening Assessments (Continued)
If Subject passed first cycle for menstrual blood loss (MBL) and has qualifying fibroids perform
Endometrial biopsy/Pap Smear (if not already performed)
Results can take days
Mammogram (if applicable) – Local Read – enter into EDC after report obtained
Schedule as soon as possible in case further imaging required
Subjects who are within 30 days of their 39 birthday approximately 2.5 to 3.5 months after they sign consent should have the mammogram performed.
Dispense additional sanitary products and collection supplies, as necessary
Perform contraception counseling and dispense contraceptives
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

13. Subject Eligible for Randomization
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

14. Protocol Reminders Margaret Kruelle

15. Repeat Procedures
Alkaline Hematin and Screening Product Collection Visits
Screening Product Collection Visit 1 results <60 mL, subject should be screen-failed
Exception: There is a reason that warrants consideration to allow for SPCV2 (e.g., Subject did not collect all products; discarded products, etc.); contact AbbVie
Use of non-validated products in Screening:
AbbVie will notify you when Subject may collect additional Screening product Collection cycles
Important to re-train subjects regarding use of study supplied sanitary products only
Screening Cycle 1 Blood Loss
Screening Cycle 2 Blood Loss
Screening Cycle 3 Blood Loss
Eligible
> 80 mL
Not needed
Yes
< 80 mL
< 80 mL*
* Study site must consult AbbVie for approval to collect sanitary products for additional menstrual cycles in Screening.
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

16. Repeat Procedures (continued)
The need to repeat a procedure may mean the difference between randomizing within 3.5 months or postponing randomization by 1-2 additional months
Most commonly repeated assessments are:
Hemoglobin level
Due to Patient-Population: Women with heavy menstrual bleeding
Hemoglobin levels are commonly low
If Hgb level is < 12 g/dL, subject should be prescribed iron supplements
If Hgb <8 g/dL, repeat Screening Hgb level after ample time to allow Hgb levels to increase; consider timing in reference to menstrual cycle
Remember to order iron supplements and stool softener when Hgb level is <12 g/dL through Pharmacy Solutions
Endometrial biopsy
After treatment for endometritis, as confirmed with SDP, scant tissue, etc.
Allow 10 days for result availability
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

17. Repeat Procedures (continued)
Ultrasound
Due to unclear static images
Discuss with imaging Tech up-front that if areas within the cavity are better viewed “real-time”, highly recommended sending in cine-clip in addition to still-images
Challenging an Imaging Result
There are limited circumstances when the imaging results from the central vendor can be challenged:
Example: Local ultrasound result differs from Central Read result (PAREXEL)
It is important that the PI (or other qualified individual) review the local report and the Central Imaging Report (PAREXEL) against PAREXEL’s report; potential misread of images may be due to unclear/static images
Obtain video clips of any areas that could be ambiguous
Notify your Monitor or AbbVie Clinical Team within 72 hours of receiving PAREXEL’s results;
Dr. Owens will review the case with PAREXEL to determine if repeat is warranted
If approved, Parexel will issue a query requesting repeat
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

18. Adverse Events Collected During Screening Margaret Kruelle

19. SAE/AE Reporting During Screening
Collected from time of Informed Consent until first dose of the study drug
Serious and protocol-related non-serious adverse events:
Collected from first dose of study drug through the 12 month Post-Treatment Follow-Up Period
All serious and non-serious adverse events:
Reporting timelines:
Serious Adverse Events (and subsequent follow-up data) reported to AbbVie within 24 hours of the site’s awareness
Pregnancy reported within 1 business day of the site’s awareness
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

20. Non-Serious Protocol Related Adverse Events – Examples
Non-Serious Adverse Events occurring during Screening should be closely evaluated by the Investigator or medically qualified Sub-Investigator to determine if they are related to the protocol
Examples of protocol related screening events include:
Infection/pain at biopsy site
Hematoma/local reaction at blood draw site
Worsening of underlying disease due to wash-out period
Dizziness
If the Subject had not eaten a meal and felt dizzy, the event may not be considered a protocol related AE and not reported as an AE in Screening
Viral infections such as flu
Would not be reported as an AE in ScreeningM12-815/817 Monthly Site
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

21. Visit Window Calculator Margaret Kruelle

22. Study Visit Windows
All visit windows in the study are based off of Day 1/Subject Randomization Monthly visits are based on a 28-day month
Example: If a subject is Randomized on 12Apr2016
Month 1 projected visit is 28 days following Day 1 which is 10May2016
Month 2 projected visit is 56 days following Day 1 = 07Jun2016
Month 3 projected visit is 84 days following Day 1 = 05Jul2017
The visit windows in treatment are ±4 days; however, if a Subject comes in within window, but not on the projected date, the next visit projected date does not change
Example:
Month 1 actual visit occurs 14May2016 (+4 days from the projected date of 10May2016)
Month 2 projected visit date does not change and is still 07Jun2016
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

23. Study Visit Windows Study Visit Windows Study Visit Visit Windows
Day 1 (Days 1 – 10 of the start of menses)
No visit windows*
Treatment Period: Months 1 – 5
±4 days
Treatment Period: Month 6
–4 or +6 days
Post-Treatment Follow-Up Period: Months 1 – 12
±7 days

24. Study Visit Calculator
A visit window calculator is available on both the M and M study portal or it can be provided by your Monitor
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

25. Assessment Specific Visit Windows
As it may not be possible to perform some procedures the same day as the main study visit, Ultrasound, DXA, Endometrial Biopsy and MRI (if applicable) have additional visit windows based on the study visit date
Assessment-Specific Windows for Treatment and Post-Treatment Period
Study Visit/Assessment
Visit Windows
Treatment Period
Day 1: Ultrasound, MRI (if participating in MRI subset)
±7 days
Month 3: Ultrasound
Month 6: Ultrasound, MRI (if participating in MRI subset) DXA and Endometrial Biopsy
–15 days
Post-Treatment Follow-Up Period
Month 3: Ultrasound, MRI (if participating in MRI subset)
–15 or +4 days
Month 6: Ultrasound, DXA
Month 12: DXA
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

26. Imaging Reminders Cenk Pusatcioglu

27. Imaging Submissions to PAREXEL
E-transfer Comments:
Comments should also be used to include any reasons for deviations from the Image Acquisition Guidelines
Sonographer/Technologist Name can be included in comments during upload
For Courier Sites:
Please be sure to include DOB and Last Menstrual Period (LMP) date for submitted images
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

28. Monthly IQC Submission
IQC Submission is Required
IQC should be acquired at least 3 times per week
The cumulative IQC database should be submitted to PAREXEL the first week of the month and with follow-up subject scans
IQC can be submitted using pseudo subject number (e.g., XXX000)
For monthly submissions, the same submission can be used for multiple studies
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

29. PAREXEL Contact Information
For questions related to Site Qualification and Image Submission, please contact:
(Note: is the best way to reach the PAREXEL Team)
FAX:
For general questions, the following team members can be contacted:
Kira Pervier           
Michael Moore   
Richard Davis     
Please be sure to include the study and site number on all communications
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

30. MRI Subset Jennifer Thomas

31. MRI Subset MRI subset is voluntary
We request that all Subjects are asked if they would like to participate
Subjects will agree to participate or decline participation in the MRI Subset
MRI consent is within Main ICF
Agreement to MRI subset in ICF is agreeing to Day 1 and subsequent MRIs
MRI Subset Time Points
Day 1
Month 6
Post-Treatment Month 3 X
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

32. MRI Not to Be Performed in Screening Unless Requested by Parexel
An MRI may be requested for Subjects in Screening who have qualifying uterine fibroids and uterine volume as assessed by ultrasound; however, SIS images cannot fully assess the endometrial cavity
If an MRI is requested in screening, a query will be issued by PAREXEL
MRIs may not be done in lieu of an SIS and the site should not perform an MRI in screening unless a query has been received from PAREXEL
Subjects having a Screening MRI and consented to the MRI subset will not have an MRI on Day 1
MRI qualification is not required for study start:
If locating an MRI facility or obtaining the test transfer images is proving challenging, please discuss with PAREXEL or Cenk Pusatcioglu (AbbVie)
Your Site can be green-lighted (start screening) without MRI
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

33. Study Drug Reminders Jennifer Thomas

34. Study Drug Reminders IRT (Trident) manages study drug allocation
Two different Kits will be dispensed to the subject
Elagolix study drug (elagolix or matching placebo)
E2/NETA study drug (E2/NETA or matching placebo)
Dosing Instructions
Elagolix or placebo – subject will take one tablet in the morning and one in the evening (BID dosing)
E2/NETA or placebo – subjects will take one capsule per day (QD dosing)
Study drug inventory
Managed by IRT
IRT will evaluate the site inventory on a daily basis to determine the need for additional drug shipments
Study drug reconciliation and accountability
Perform in IRT
Monitor will conduct accountability during study visits
Monitor returns study drug to AbbVie
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

35. Study Drug Compliance Jennifer Thomas

36. Study Drug Compliance
Study drug compliance will be monitored each time a subject has returned study drug
Compliance technology is built into each kit (Med-ic software)
To conduct compliance monitoring:
Sites will be provided with laptop with loaded software
Training videos and modules on laptop
One (1) scanner per site, provided separately; used to scan compliance technology
Expectation is to scan kits while subject at site to re-educate and/or provide positive feedback
Each of the Site Staff Personnel must complete registration form to gain access to Med-ic software
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

37. KCAS Sanitary Product Collection Reminders Pierre Philippe

38. Sanitary Collection Reminders:
Measuring Menstrual Blood Loss and Sanitary Product Collection are key components of the study: Primary Endpoint
Please remind subjects to use only validated sanitary products provided for the study
Instruct subjects not to combine sanitary products from more than one day into the same bag 
Remind subjects to discard all pad wrappers, toilet paper, adhesive strip papers and tampon applicators. (Do not include these items in the clear plastic bags)
All products used in anticipation of menses, even if no visible blood on product, must be handled as if there were blood:
Collect all products for each day
Insert into clear plastic bags and then into the daily white plastic bag
In Comment Section on KCAS Site Requisition Form, indicate in comments that products were worn in anticipation of menses
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

39. Sanitary Collection Reminders:
Subjects need to collect products whether there’s visible or no visible blood
If the subject uses (by accident) any sanitary products not provided by the site, please remind her to collect and return these products
Please review Sanitary Product Collection process and compliance with Subject (before Subject leaves site)
Review both the KCAS Site Requisition Form and KCAS Subject Requisition Form with the subject, ensuring all entries are accurate and complete
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

40. KCAS Reminders
Prior to dispensing, it is strongly recommended that site personnel review with the subject (in person) how to complete the white bag label and the Subject Requisition Form
Use this form and questions as a learning tool to re-educate and/or to remind Subjects of proper handling
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

41. Vendor Support Pierre Philippe

42. Clinigen - Nutritional Bars/Drinks
Clinigen distributes Nutritional Bars and Drinks to sites in US and Puerto Rico
Intended provision of these products to subjects
Long visit durations
Visits requiring fasting clinical safety labs (provide after blood draws)
Provide maximum of 1 bar and 1 drink per subject per aforementioned
Managing Orders
Initial shipment is ordered through AbbVie
Subsequent orders: managed by you (Study Site)
Check inventory on an ongoing basis
Varieties:
Zone Perfect Bars
Ensure Original (chocolate and vanilla)
Ensure Complete (chocolate and vanilla)
Glucerna (chocolate and vanilla)
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

43. Central Recruitment Continuum Clinical: Central Advertising
Websites:
Main Website: MyFibroidStudy.com
Referral websites to track how potential subjects were identified (e.g., Community Outreach, Health Fairs, etc.):
MyUFStudy.com
Womenwithfribroids.com
Television and Radio advertising
Digital (Facebook, Search Engine Marketing, Social Media, Healthcare Websites, etc.)
Print (Newspaper, Magazines, Direct Mail, etc.)
Media Placement
Currently limited markets
Depending on media market: Based on number of and when Sites are green-lighted
Summer (June and August): markets even more limited
Full campaign with broadest reach starts September
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

44. Continuum Clinical (Continued)
Referrals:
If you are in a media-placement market and you do not want to receive referrals, contact AbbVie or communicate directly to your Continuum Site Optimization Specialist (SOS) contact
If you are receiving referrals and cannot process referrals within 72 hours, or have reached maximum capacity, notify SOS contact
We want to be proactive
Maximum limits can be set
Overflows can be shifted to other Sites within your region
ThreeWire support: Please consider how they can assist
Weekly monitoring of referral processing
AbbVie may make executive decision to alter referral numbers to Study Sites
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

45. ThreeWire
Partnering with sites and practices to provide an “extra pair of hands” when and where needed most to assist in recruitment enrollment and retention
Chart Review
Reviewing medical charts
Enrollment Assistants
Additional support for Referrals and database-identified Subjects
Phone screening
Processing media referrals
Scheduling appointments
Data entry
Distributing approved study recruitment materials
Tracking subjects’ status in My-Patient.com
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

46. mProve
mProve - Mobile application provider that allows subject to use own personal phone to receive reminders via text or push notifications
Subject Reminder Messages to Support the Following Activities
Attend/confirm Study Visits
Keep Engaged
Keep in Touch
Complete the Study
Sanitary Product Collection
Contraceptive Use
Working out final details (text messaging, programming); expect to launch by August
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

47. Financial Disclosure Certification Pierre Philippe

48. FDC - Financial Disclosure Certification
Federal Regulations 21CFR54 require disclosure of financial interests for all Investigators or Sub-Investigators participating in the conduct of the study
The Financial Disclosure Certification needs to be completed as part of Essential Document packets prior to activation and details should be provided regarding the nature of all financial arrangements for all “Yes” responses checked on the form
A Unique address must be provided for all Investigators and Sub-Investigators listed on the FDA1572, otherwise the form will be rejected
Your Site cannot be “green-lighted” (approved to start Screening) unless unique addresses are provided for each individual listed on FDA1572
If there is any change in the accuracy of the disclosure during the term of the study and up to 1 year post study participation, it is the responsibility of the Investigators or Sub-Investigators to notify AbbVie without delay
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

49. FDC Form
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

50. Frequently Asked Questions (FAQ) Jennifer Thomas

51. Mammogram
Question: If a mammogram at Screening contains a recommendation for ultrasound or repeat scan of either breast, would subjects still be eligible? Do we need permission for extra views for mammograms?
Answer: The protocol allows additional imaging to be performed. If results of those images show BI-RADS 1-3 or equivalent, the subject would be eligible based on the mammogram criterion. If further diagnostic testing such as a biopsy are recommended, the subject would need to be screen failed
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

52. ECG
Question: My Site’s ECG machine automatically calculates and reports both QTcF and QTcB.  Is this acceptable?
The ECG machine calculated the QTc values as follows: QTcF = QTcB = 465
Answer: Sites that have ECG machines that calculate both Fredericia and Bazett should decide which correction factor to use before Screening subjects and use that single correction factor consistently for all subjects at that site and throughout the study.
If the QTc is >450 msec during Screening, the subject is not eligible. For further guidance sites can feel free to consult with a cardiologist.
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

53. ECG
Question: What are the options for sites that don't have an ECG machine that has QTcF calculation?
Answer: For sites that don't have an ECG machine that performs the QTc calculation, they can either rent a machine that does the calculation or have a cardiolgist calculate the QTc. We allow both Fredericia (QtcF) and Bazett (QTcB) calculations to be used ( each site should select only one correction factor for their site and consistently use that one for all study subjects and for the duration of the study).
Under certain circumstances, AbbVie may assist with the rental of an ECG machine. Prior approval must be received.
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

54. FSH
Question: If the FSH is out of range (>35), can the lab be re-tested since FSH levels can spike around ovulation?
Answer: Subjects with a Screening FSH level >35 are not eligible for the study. Sites should consult the AbbVie SDP if they would like to discuss subjects with FSH levels > 35.
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

55. Randomization Menses
Question: Regarding the menses which occurs during the actual Randomization, does the subject collect sanitary products for that menses as well?
Answer: Yes, subjects are required to collect sanitary products for their randomization menses and would return the keg within approximately 5 days after cessation of bleeding or spotting. If subject’s bleeding ends by the time of Randomization (Day 1-10 of menses) subject can return at Day 1. If not, she can return after Day 1 within approximately 5 days after cessation.
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

56. Stipend
Question: If a subject has to return to the site for a repeat procedure, will she be reimbursed for that visit?
Answer: Yes, if a subject has to return to the site for a repeat procedure or an Unscheduled Visit, the subject will be paid for the visit.
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016

57. Questions
M12-815/817 Monthly Site Telecon May 10&12, 2016 | Company Confidential © 2016