Trial Compares Results with NACTN Registry

Posted by Sam Maddox in Research News on June 06, 2017 # Research

It’s true for almost all spinal cord injuries: A certain amount of recovery happens on its own. That of course sets up a fundamental question whenever results are claimed for some sort of treatment or intervention:

How do you know for sure if the improvement was because of what you did, and not just part of a natural, spontaneous recovery?

Animal studies use defined species and standardized injuries to compare the recovery of a group that receives an experimental treatment with a group that receives no treatment. That’s not so easy to do in human studies – SCI is rare, and extremely heterogeneous. Two cases are seldom the same in terms of location and severity of trauma. It’s also hard to control for natural recovery, even with well-matched subjects, because of ethical concerns related to exposing trial participants to undue risk if the non-treatment arm (e.g. the placebo group) is exposed to an invasive procedure.

This brings up InVivo Therapeutics, a publicly traded biotech in Cambridge, MA. The company is currently running a clinical trial for a dissolvable polymer scaffold surgically implanted within the injury site in the first few days after acute spinal cord injury. The premise is that the scaffold will promote regrowth of nerve fibers across the injured area and reduce cavitation and scarring, thus improving neurological recovery.

The full title is the “INSPIRE Study: InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold for Safety and Neurologic Recovery in Subjects With Complete Thoracic AIS A Spinal Cord Injury.”

The InVivo trial began in 2014 and now has 31 clinical centers planning to enroll 20 patients with thoracic SCI (T2-T12/L1). The primary endpoint is to improve ASIA Impairment Scale (AIS) of one or more levels at six months. (That means, for example, going from complete to incomplete injury.) The study is measuring motor score changes, as well as changes in bowel and bladder function, pain, and quality of life.

InVivo has reported in press releases that patients with the implanted scaffold have experienced improvement in neurological function. However, to be convincing that their recovery exceeds the natural rate of recovery it is necessary to have a control group, or at least a valid comparison group of patients with similar injuries who had received the best standard care for spinal cord injury.

So InVivo turned to the Reeve Foundation’s North American Clinical Trials Network® (NACTN) acute SCI registry to establish a baseline upon which to compare its trial results.

NACTN, also supported by the Department of Defense, comprises nine clinical centers (all but one in the U.S.) aligned to streamline trial logistics and reduce administrative friction in testing potential therapies. The Network has completed a Phase I trial of the neuroprotective drug Riluzole in acute SCI and is now engaged in a Phase II/III trial of the drug.

Since 2005 NACTN has collected very detailed information about people with acute spinal cord injuries, including accident specifics, medical history, neurologic tests and motor/sensory measures, as well as measures of body systems including heart, lungs, blood pressure, urinary tract, digestive tract, infection incidence, and psychiatric measurements. In all, the registry tracks over 1000 information points for a full year post-injury.

There are at least two other large SCI clinical databases, EMSCI (European Multicenter Study about Spinal Cord Injury), which hosts about 2000 patient records, and the U.S. Model Systems database, which has data going back to the 1970s and includes about 32,000 patients.

NACTN’s main advantage with regard to InVivo is that the SCI registry is focused on safety and course of recovery in the acute phase of injury. Robert G. Grossman, M.D., a neurosurgeon at Houston Methodist Hospital, has overseen the NACTN project from the start. “The NACTN registry is the only database that gathers detail on the immediate acute phase during the initial hospitalization after spinal cord injury,” said Grossman. To date, the NACTN SCI registry has enrolled 875 patients.

“We developed procedures to share the registry,” Grossman said. “We’re here to support the field in general and to move it forward. The idea behind the registry is to provide a baseline of information in clinical trials, especially for Phase I trials that need to know if the treatment or medication is safe. By their design Phase I trials do not have a control group, so our data becomes important to measure both safety and outcome.”

The numbers of patients in the NACTN database with T2-T12/L1 injuries won’t be large but should offer the company a way to compare its scaffold implant results against what usually happens as thoracic SCI recovers naturally.

From InVivo press release (they call the thoracic comparison study CONTEMPO).

InVivo believes that the combined information in the INSPIRE study and the CONTEMPO Registry Study will provide a rigorous body of evidence for the demonstration of safety and probable benefit as required by the Humanitarian Device Exemption (HDE) approval process, and plans to submit the two studies together for HDE approval.

James Guest, M.D., Ph.D., a member of InVivo’s Scientific Advisory Board, a NACTN investigator, and the Principal Investigator of the CONTEMPO Registry Study, said, “The NACTN Registry was developed in large part to aid in the interpretation of SCI clinical trial results. This is the first time that the registry will be used with a partner in industry, and I believe that the registry will provide a valuable benchmark for analysis of INSPIRE results.”

Mark Perrin, InVivo’s Chief Executive Officer and Chairman, said, “We are grateful for the care and vigilance that NACTN has put into developing an impressively thorough, curated database over many years. The inclusion of the NACTN Registry substantially increases the strength of the CONTEMPO Registry Study.