Intradiscal treatment with recombinant human MMP-7 for patients with lumbar disc herniation: A sham-controlled multicenter, single-blind, dose-escalation, single-dose, phase I/IIa study.

Abstract

Background: This sham-controlled multicenter, single-blind, dose-escalation, single-dose, phase I/IIa study aimed to validate the safety and exploratory efficacy of intradiscal administration of recombinant human (rh) MMP-7 (KTP-001) for patients with lumbar disc herniation.

Methods: The cohort consisted of three groups. Cohort 1 (C1): three patients in the Sham group, three patients in the KTP-001 X-μg group. Cohort 2 (C2): six patients in the KTP-001 2X-μg group. Cohort 3 (C3): six patients in the KTP-001 4X-μg group. Under X-ray guidance, KTP-001 was injected into center part of the intervertebral disc at the level of herniated disc. The patients between the ages of 20 and 60 years had a subligamentous extrusion type of lumbar disc herniation at the L3-L4, L4-L5, or L5-S1 level. Adverse events, vital signs, clinical tests, magnetic resonance imaging (MRI), X-ray images, and anti-KTP-001 antibodies were used as primary endpoints to evaluate the safety of the investigational drug. The secondary endpoints were low back and leg pain intensity, neurological findings, Oswestry Disability Index, serum keratan sulfate pharmacodynamics, and hernia size on MRI to evaluate exploratory efficacy. The observation period was up to 24 weeks after administration.

Results: A total of 19 patients participated in the trial. No adverse events resulted in death or led to treatment discontinuation. Furthermore, CTCAE Grade 3 or higher adverse events did not occur. No changes were observed in the intervertebral discs or endplates that could be strongly attributed to drug administration based on MRI and X-ray radiographic. All the subjects remained negative for anti-KTP-001 antibody. Early after the treatment, we observed statistically significant improvements in neurological findings, SLR test results, and ODI results.

Conclusions: Even if administered immediately after the onset of the disease and confirmation of the diagnosis, intradiscal treatment with KTP-001 may be safe and tolerable.