Mainstay Medical International, a medical device company focused on commercialising ReActiv8, an implantable restorative neurostimulation system designed to treat an underlying cause of disabling chronic low back pain, announces headline results from its ReActiv8-B study.
The ReActiv8 B clinical study is an international, multicentre, prospective, randomised, active-controlled, blinded trial with one-way cross-over, conducted under an Investigational Device Exemption (IDE) from the US Food and Drug Administration (FDA). A total of 204 patients were implanted with ReActiv8 at leading study centres in the USA, Europe and Australia and randomised 1:1 to therapy or control 14 days after implant. In the treatment group, the ReActiv8 pulse generator was programmed to deliver electrical stimulation expected to elicit contractions of the multifidus muscle. In the control group, the ReActiv8 device was programmed to provide a low level of electrical stimulation. Following assessment of the primary endpoint at 120 days, patients in the control group crossed-over to receive levels of electrical stimulation as in the treatment group.
The patients in the study had an average age of 46, and an average duration of chronic low back pain of 14 years. This patient population has tried many other treatment alternatives with limited success, and 80% of the patients were on pain medication at baseline.
Efficacy outcomes
The primary efficacy endpoint of the study was a comparison of responder rates between the treatment and control groups as measured on the visual analog scale (VAS) of pain, with responders defined as having a 30% or greater improvement on this measure between baseline and 120 days after randomisation, without any increase in pain medication taken in the two weeks prior to the primary endpoint assessment visit. In the treatment group the responder rate at 120 days was 56%, compared to 47% in the control group, resulting in a difference that is not statistically significant.
ReActiv8-B is the first ever active sham-controlled clinical trial of an implantable neurostimulator for chronic low back pain. The literature from other sham or placebo-controlled studies, involving drugs, device implants or other interventions, suggested that a responder rate of 20% or more could have been expected in the control group. The study design assumed a 25% responder rate in the control group.
“Our study involved surgically implanting a device into patients who had not previously received surgical implants, and further required the patient to activate the device twice daily to administer the therapy,” said Jason Hannon, CEO of Mainstay. “The study design underestimated the amount and duration of the sham effect under these conditions.”
“The overall results of this study, however, are a solid endorsement of the efficacy and safety of ReActiv8,” continued Hannon. “We saw very high responder rates in the patients in the treatment group that have reached one year of therapy, and substantial improvement in the patients that were crossed-over to treatment from the control group after 120 days. We believe these long-term results represent the most important clinical factors to physicians, and we plan to leverage these results in continuing to drive our commercial business under our existing CE Mark in Europe.”
Responder rates grow to one year
Improvements in the percentage of patients reporting pain reduction continued beyond the 120-day assessment through one year for both groups. The percentage of the 56 patients in the treatment group that have completed the one-year assessment having a 30% or greater reduction in low back pain VAS at that assessment without an increase in pain medication was 75%. The percentage of the 60 patients in the cross-over group that have completed the one-year assessment having a 30% or greater reduction in low back pain VAS at that assessment without an increase in pain medication was 68%. The percentage of the 116 patients in the both groups that have completed the one-year assessment having a 50% or greater reduction in low back pain VAS at one year without an increase in pain medication was 60%. Substantial improvements in disability as measured by the Oswestry Disability Index (ODI) were also observed at one year. These data are subject to change as the remaining patients reach the one-year assessment.
“The totality of this data is encouraging for this large group of patients with limited treatment alternatives,” said Chris Gilligan, chief, Division of Pain Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women’s Hospital, Assistant Professor of Anaesthesia, Harvard Medical School, and principal investigator for the study. “The data on the patients that have completed one year of therapy are important, particularly because these patients have not experienced meaningful pain relief from existing treatment options. The data showing 60% of patients experiencing a 50% or greater pain reduction at one year surpasses what many implanting physicians expect from implantable neurostimulation devices.”
Results demonstrate voluntary decrease in back pain medication use
The protocol permitted patients to adjust their back pain medication usage after the 120-day assessment point. At one year, 44% of the 50 patients who were on opioids at baseline had voluntarily eliminated (28%) or significantly reduced (16%) their use of opioids. These results are subject to change as the remaining patients reach the one-year assessment.
Secondary endpoints
For secondary endpoints, such as disability measured by the ODI and quality of life measured by the EQ-5D quality of life instrument, numerical improvements in the treatment group as compared to the control group were observed at 120 days. The Company is evaluating the clinical significance of those findings. The Company continues to analyse the efficacy data for the purpose of better understanding the performance of the device.
Device-related adverse events in line with other studies
ReActiv8 is implanted in a minimally invasive procedure utilising techniques commonly used by our physician customer base in other procedures. The incidence and type of adverse events (AEs), including serious AEs, were comparable to AEs in clinical trials reported for other neurostimulation devices, with no unanticipated AEs related to the device, procedure or stimulation.
“The study showed a comparable safety profile to other implantable neurostimulation devices, including no migration of leads,” said Richard Rauck, president and founder, Carolinas Pain Institute, Medical Director for The Center for Clinical Research, Pain Fellowship Director at Wake Forest University School of Medicine and chairman of the DMC. “This safety profile, combined with the efficacy data from this study and the lack of available alternatives for this patient population, suggest that ReActiv8 can be a promising therapy for patients with chronic low back pain.”
Pre-market approval plan
“In summary, we believe the evidence of effectiveness and the favourable safety profile of ReActiv8 show considerable promise, particularly when compared to the response rates and safety profiles of alternative treatments,” continued Hannon. “We believe that the totality of the data will support the submission of a PMA application for ReActiv8 to the FDA. We plan to seek a pre-PMA meeting with the FDA in the coming months to obtain guidance on our filing content and strategy.”
