Background & Aims
There is an increasing need to find innovative pathways to shorten clinical trial timeframes to bring much needed medicines to patients faster and at reduced costs. Master protocols are designed to evaluate multiple lines of inquiry and may be used to assess one or more interventions in multiple diseases or multiple interventions in a single disease. Compared to a collection of independently conducted trials, a well-designed and executed master protocol can more efficiently maximize information obtained from research efforts to accelerate drug development [1]. The Phase 2 Chronic Pain Master Protocol (H0P-MC-CPMP; CPMP) was the first known application of this design to chronic pain and efficiently coordinated randomization of patients with 3 different pain types across 4 separate intervention substudies following the concepts of a platform trial design. Here we present operational metrics including internal and external efficiencies observed during the CPMP.
Methods
The CPMP (a randomized, double-blind, placebo-controlled, Phase 2 proof-of-concept trial) started at 34 US sites. Periodic in-trial site performance reviews resulted in site removal or addition. The CPMP entered the FDA’s Complex Innovative Design Pilot Program June 7, 2019, with First Patient Visit May 2020 and first patient dose July 2020. It assessed safety and efficacy of 4 potential novel chronic pain interventions (LY3016859 Epiregulin/TGF? monoclonal antibody, LY3526318 transient receptor potential ankyrin 1 antagonist, LY3556050 somatostatin receptor 4 antagonist and LY3857210 purinergic 2X7 antagonist) vs placebo in patients with osteoarthritis of the knee, chronic low back pain and diabetic peripheral neuropathic pain. All 4 substudies evaluated reduction in average pain intensity as primary outcome with a numeric rating scale. Patients were randomized 2:1 study drug:placebo, which allowed for placebo borrowing. Drug substudies entered and exited the CPMP at different times.
Results
Despite the intensive setup, CPMP demonstrated substantial optimization and timeline reduction across site activation, enrollment, issue management and data readouts by the second substudy. Several operational factors, including consistent resources across medical, operations and statistical teams; ability to transfer data within a single database; integrated Spotfire and SoCool dashboards for blinded safety data reviews; a detailed Manual of Operations; color coding to align protocols, lab kits and questioners for each substudy; and maintenance of a uniform investigator footprint across all substudies, were key to CPMP’s optimization. These factors led to progressive site-level expertise, enhanced continuous screening, rapid data turnaround times, and reduced enrollment timelines from 8.3 to 4.7 months despite a site footprint reduction from 34 to 30 sites and cost reductions due to economies of scale.
Conclusions
The CPMP design enables efficient testing of multiple investigational interventions across a variety of pain types while allowing study interventions to be added at different time points across patient populations. At the same time, the use of standardized design elements and dedicated resources within the overall context of this flexible design resulted in reduced enrollment timelines and operational efficiencies at several levels.
References
1.Woodcock, J. and L.M. LaVange, Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both. N Engl J Med, 2017. 377(1): p. 62-70.
Presenting Author
Lucía Pérez
Poster Authors
Lucía Pérez
MS
Eli Lilly and Company
Lead Author
Mario Sgro
MS
Eli Lilly and Company
Lead Author
Shelly Houck
MS
Eli Lilly and Company
Lead Author
AnnCatherine M. Downing
PharmD
Eli Lilly and Company
Lead Author
Phebe Kemmer
PhD
Eli Lilly and Company
Lead Author
Garrett Adams
MBA
Eli Lilly and Company
Lead Author
Arif Khan
MD
Northwest Clinical Research, Seattle, WA
Lead Author
Virginia Stauffer
PharmD
Eli Lilly and Company
Lead Author
Virginia Stauffer
Eli Lilly
Lead Author
Topics
- Trial Design