NF-kappa B Oligo DNA decoy provides 12 months of pain relief and disc height restoration for patients with chronic discogenic low back pain-a randomized clinical trial.

Abstract

Background context: Low back pain is responsible for patient disability, extraordinary health care costs, and significant loss of productivity. Inhibition of the NF-κB-mediated signaling pathways by AMG0103, an NF-kappa B oligonucleotide decoy, may result in a reduction of pro-inflammatory cytokines and catabolic enzymes involved in intervertebral disc disease and pain.

Purpose: To evaluate the safety, tolerability and preliminary efficacy of AMG0103 in patients with chronic discogenic low back pain.

Study design: A Phase 1b, multicenter, double-blind, randomized, placebo-controlled, single ascending-dose clinical study.

Patient sample: Patients with chronic symptomatic single level discogenic pain for at least 6 months, where back pain is greater than leg pain.

Outcome measures: Self-reported Measures: VAS, ODI, PGI-C, RMDQ Physiological Measures: adverse events, laboratory values, and imaging METHODS: Patients with chronic discogenic back pain for more than 6 months who had failed at least 3 months of conservative care were evaluated. Inclusion criteria designated a Pfirrmann score of 3 or 4, with or without contained disc herniations of ≤3 mm protrusion, and disc height loss of the symptomatic disc is less than 50% of the adjacent discs. Nineteen adult patients received AMG0103 (0.3, 3.0 and 10.0 mg), an NF-kappa B oligo DNA decoy, while 6 patients received a placebo injection of phosphate buffered saline directly injected into the intervertebral disc. Safety and preliminary efficacy patient-reported outcome measures were obtained through 12 months in a 2-part study.

Results: The safety of AMG0103 was confirmed through an absence of neurologic, sensory or motor function decline in the placebo and all treatment groups. Additionally, there were no clinically relevant renal, hepatic or hematologic dysfunctions. Moreover, a single injection of AMG0103 resulted in a dose-dependent and sustained reduction in back pain, measured on a 100 mm VAS scale, with the high dose reaching a mean pain reduction of 77% and a median pain reduction of 97.5% compared to baseline at 12 months. Further, disc height declined by 0.25 mm at 12 months for the placebo group, while the 10 mg AMG0103 cohort disc height increased by 0.31 mm over the same period. Dose dependent improvements were also seen via PGI-C, RMDQ, and ODI, with a reduction in rescue medications for AMG0103 patients.

Conclusion: A single intradiscal injection of AMG0103 demonstrated clinically meaningful and statistically significant improvements in back pain, disc height and patient satisfaction throughout 1 year. Further investigation in a larger patient population is warranted.