CASE STUDY
P R A H E A LT H S C I E N C E S
P RA L E A DS N OVE L MU LTIP L E MY E LO MA DRU G DE V E LO P ME NT P RO GR AM Expanded Access Program Follows Accelerated Approval
P R A H E A LT H S C I E N C E S C A S E S T U D Y
P R A LEA DS N OV E L M U LTIP L E MY E LO MA DR U G D EVELO PM E N T P RO G RA M Expanded Access Program Follows Accelerated Approval STUDY D ESC RIP TIO N
Study 1: A randomized comparison of Study Drug A against high-dose Study Drug B in patients with relapsed or refractory multiple myeloma that served as a pivotal trial to support conversion of Study Drug A’s accelerated subpart H approval to a regular approval (669 patients), published in the New England Journal of Medicine in 2005 Study 2: A single-arm expanded efficacy and safety study for patients with refractory multiple myeloma who were ineligible for the pivotal trial and for patients randomized to the control arm of the pivotal trial to allow “rollover” to Study Drug A PRIMARY ENDP OINT
Response & Overall Survival
STU D Y D U RAT I O N
27
MONTHS
PRIMARY SE RV ICE S
Full Service Project Management Drug Safety Safety Reporting IND ICATION
Multiple Myeloma D RUG CLASS
Biologic
N o . O F C LI N I C AL S I T E S
105
PAT I E NT P O P U L AT I ON
1,100
RE G IO NS
United States Europe Middle East
STUDY PHAS E
Phase III
BUSINESS SE G ME NT
Product Registration
SI T UAT I O N
PRA Health Sciences supported 2 multiple myeloma clinical trials, a Phase III and a “rollover,” for a large biotech client, which enrolled more than 1,100 patients globally at a rate of approximately 0.3 patients/site/month. The Phase III study included 50 sites, and with the addition of the “rollover study,” grew to 105 sites. PRA assisted the client with the design of the trial and quickly assigned resources to the project for rapid study start-up. At its peak, the trials employed 58 PRA clinical team members and 32 additional data and safety team members. PRA’s project team had extensive in-house training to reinforce the intricacies of myeloma monitoring. This was difficult even for experienced oncology monitors because of the immunological chemistry inherent in the trial. PRA invested in multiple training sessions, which enhanced the monitoring team’s performance throughout the trial.
THE FUTURE OF CLINICAL DEVELOPMENT.
P R A H E A LT H S C I E N C E S C A S E S T U D Y
In addition, PRA managed all pre-/post-marketing individual safety case reports outside the United States. The program included more than 70 studies (Phases I-IV) and 1 expanded access program across 60 countries. More than 2,000 reports were received, 50% with reportable events. On average, more than 40 suspected serious adverse reactions were reported and investigated each month, and an average of 915 safety letters were distributed to investigators/ethics committees. PRA’s safety training program enabled us to increase the workforce for this project from 20 to over 40 staff members globally, including safety and support staff (ie, project management), as commercial product sales grew. This management contract was one of the largest on record in the ongoing research for multiple myeloma treatment. PRA’s clinical team provided enhanced communication and site support, enabling PRA to streamline regulatory document collection to quickly activate sites. Approved by the FDA after a 4-month accelerated approval process, the drug is the first in a new class of anti-cancer agents called proteasome inhibitors. R E S U LTS
Over the course of the studies, PRA accomplished 3 interim calls for data, collecting 99% of the required data on time. PRA’s success with the multiple myeloma projects can be directly attributed to our: • Scientific and clinical expertise with the disease. • Knowledge of European regulatory guidelines. • Cohesive, well-trained teams—including management and monitors. • Knowledge of the sites and their ability to enroll patients. • Client relationships built on trust and respect. One of the keys to PRA’s success with these trials was our ability to capitalize on the firm foundation the client had established on its Phase I/II program (eg, the client enrolled a large number of patients, had excellent study design, and assembled a first-class team of multiple myeloma investigators and thought leaders). The studies also provided PRA with unparalleled insight into the most effective and efficient ways to conduct multiple myeloma trials. PRA continues to apply the best practices from this experience, particularly from the trials involving patients with relapsed disease, such as: Provide early training and regular retraining of sites, specifically in defining prior regimens and the expectations for eligibility following the disease endpoints, protocol schedule, and dose modifications. Engage medical monitors with clinical experience treating multiple myeloma to: n Confirm patient eligibility before randomization. n Conduct the principal endpoint in “real-time” because sites often have difficulty assessing disease response per protocol. n Communicate frequently with the investigator throughout the trial. Select a central laboratory that will ensure reporting consistency and ease in evaluating disease response. Offer sites vigilant support to negate overwhelming patient management and study requirement requests.
“We really want to have PRA do the processing outside the US; their quality is exceptional!” — CLIENT’S ASSOCIATE DIRECTOR OF CLINICAL OPERATIONS
PRA Health Sciences conducts comprehensive Phase I-IV biopharmaceutical drug development. To learn more about our solutions, please visit us at prahs.com or email us at
[email protected] .
THE FUTURE OF CLINICAL DEVELOPMENT.
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