2. Partners in the Study Enterprise: Sponsor, CRO & Large Site Networks
SCOPE Conference
February 23, 2016

3. Partners in the Study Enterprise
Sponsor:
Trevi Therapeutics, Inc.
Vicki Duvall, RN, BSN
Director, Global Site Management and Clinical Monitoring
CRO with Investigative Site Network:
Frenova Renal Research
Brigid Flanagan, MS, RN, CCRC
Senior Director, Clinical Development

4. Partners in the study enterprise
Results:
The studies were completed 6 months ahead of schedule
Every site selected enrolled patients*
Successful partnerships established for Phase III and/or future studies
January 15, 2013
New Research from Tufts [CSDD] Characterizes Effectiveness and Variability of Patient Recruitment and Retention Practices
While nine out of 10 clinical trials worldwide meet their patient enrollment goals, reaching those targets typically means that drug developers need to nearly double their original timelines, according to new research from the Tufts Center for the Study of Drug Development, benchmarking patient recruitment and retention practices. Tufts CSDD said its recent analysis, based on more than 150 clinical studies involving nearly 16,000 sites, will help clinical research professionals better plan and manage clinical trials. "Patient recruitment and retention are among the greatest challenges that the clinical research enterprise faces today, and they are a major cause of drug development delays," said Ken Getz……
* Tufts Center for the Study of Drug Development, January 15, 2013

5. Partners in the Study Enterprise
Usual scenario:
Sponsor selects CRO
CRO identifies sites
Site qualification visit occurs
Site selection based on a number of criteria
Sponsor input e.g. KOLs
Prior history with CRO
Investigator experience
Potential enrollment
Investigators typically respond to say they can enroll 8 to 10 patients.

6. Partners in the Study Enterprise
This scenario:
Sponsor identified more than one CRO
Sponsor identified site networks
Kick off meeting attended by representatives of all parties
Input provided on
Protocol design
Feasibility questionnaire
Lessons learned from prior studies in patient population
PPD and River City (FQ only)
DaVita and FMS: Large Dialysis Organizations (LDOs)

7. Partners in the Study Enterprise
This scenario:
Sponsor focused on one product to treat moderate to severe chronic itch
Lead indication
Uremic Pruritus: chronic itch in patients on kidney dialysis. No approved therapies in US or EU
Uremic Pruritus: a chronic itching sensation in ESRD patients on dialysis, without evidence of any other active disease to explain the pruritus
Estimated prevalence ~ 84% in dialysis patients* (frequently unreported)
Brigid: Please note: The Mathur et al paper was based on a study using healthcare related quality of life instruments to measure daily itching or nearly daily by 84% of patients whose itching had gone on for > 1 year. Please also note that this study only looked at 103 people. In a larger scale study, the Dialysis Outcomes and Practice Patterns study (DOPPS), 42% dialysis patients experienced itch. I think you can say that UP is a complication of CKD but is hard to characterize. However it is measured, it is a problem for dx patients and thus needs to be addressed.
*Mathur et al, A Longitudinal Study of Uremic Pruritus in Hemodialysis Patients, Clin J Am Soc Nephrol Aug; 5(8): 1410–1419

8. Partners in the Study Enterprise
Study Challenges: Many challenges for sites and sponsor throughout study
Multiple protocol amendments
Increased protocol deviations
Extra regulatory workload
Electrocardiograms
Vendor added after the study started
No standardized equipment
Site experience varied/GCP issues

9. Partners in the Study Enterprise
Study Challenges (continued):
Labor intensive for study staff
Patient visit compliance
Numerous QoL Surveys
Protocol deviations
Problematic blister card design
Non-compliant patient population
Change in IP destruction policy midway through study
Lack of experience in trials using oral IP at some sites
GCP issues

10. Partners in the Study Enterprise
Study Challenges (continued):
EDC/Clinical Monitoring
EDC not ready to go “live” at study start up
Rapid enrollment resulted in backlog of data to be monitored
Monitors changed more than once at some sites
Quality issues identified at some sites
CRO change midway through the study

11. Partners in the Study Enterprise
Lessons learned included:
CRAs need a strong clinical background
Tools or questionnaires used must be designed with the end user in mind
Schedule of Events should align with standard of care where possible
Seek input from Investigators prior to finalizing the protocol and with subsequent amendments
…and preferably have experience monitoring the CKD population

12. Partners in the Study Enterprise
Lessons learned included (continued):
Sick patient population with multiple AEs & SAEs
Increased compliance issues with poly pharmaceutical study populations
Labor intensive study design require more onsite time for monitoring
EDC should ‘go live’ prior to starting enrollment
Sponsor/CRO/Site Network should be prepared to dedicate resources for additional training at identified sites

13. Partners in the Study Enterprise
Lessons Learned (cont):
Important to choose and place all study vendors before study start-up.
Sponsor to CRO match is crucial for trial success.

14. Partners in the Study Enterprise
In Conclusion:
Despite these challenges, the study met enrollment goals early, locked the database ahead of schedule, and achieved a statistically significant study result.
Testimony to the hard work and dedication of the sites involved and the successful partnership between the Sponsor, CRO, and large site networks.