Randomised, double-blind, placebo-controlled, parallel-group, multicentric, phase IIA clinical trial for evaluating the safety, tolerability, and therapeutic efficacy of daily oral administration of NFX88 to treat neuropathic pain in individuals with spinal cord injury

Abstract

Study design: Double-blind, randomized, placebo-controlled, parallel-group multicentric phase IIA clinical trial.

Objective: To assess the safety and tolerability of oral administration of NFX-88 in subjects with chronic spinal cord injury (SCI) and explore its efficacy in pain control.

Setting: A total of 7 spinal cord injury rehabilitation units in Spain.

Methods: A total of 61 adult with traumatic complete or incomplete spinal cord injury (C4-T12 level), were randomised 1:1:1:1 to a placebo, NFX88 1.05 g, 2.1 g, 4.2 g/day for up to 12 weeks. The placebo or NFX-88 was administered as add-on therapy to pre-existing pregabalin (150-300 mg per day). Safety and tolerability were evaluated, and the Visual Analogue Scale (VAS) was the primary measure to explore the efficacy of NFX-88 in pain control.

Results: No severe treatment-related adverse effects were reported for any of the four study groups. 44 SCI individuals completed the study and were analysed. The data obtained from the VAS analysis and the PainDETECT Questionnaire (PD-Q) suggested that the combination of NFX88 with pregabalin is more effective than pregabalin with placebo at reducing neuropathic pain (NP) in individuals with SCI and that the dose 2.10 g/day causes the most dramatic pain relief.

Conclusions: NFX88 treatment was found to be highly safe and well tolerated, with the dose of 2.10 g/day being the most effective at causing pain relief. Thus, the promising efficacy of this first-in-class lipid mediator deserves further consideration in future clinical trials.

Fig. 1. Clinical trial design.

NFX88 treatment started after Visit 1 (V1). V2, V3, and V4 (EoT, end of treatment) were carried out after 1, 2, and 3 months of treatment, respectively. During the last month, participants did not receive NFX88, and a final follow-up visit (V5, EoS, end of study) was carried out to determine the effect of NFX88 withdrawal.

Fig. 2. Chronogram.

D: days of treatment with respect to the treatment initiation (D1, day 1). For other details, see text.

Fig. 3. CONSORT flow diagram.

The diagram shows the disposition of all subjects included in the study.

Fig. 4. Distribution of adverse events.

AE: Number of adverse events; N = Number of participants reporting the AE; Placebo: 15 participants; 1.05 g/day: 15 participants; 2.10 g/day: 15 participants; 4.20 g/day: 16 participants.

Fig. 5. VAS scores in SCI individuals.

A Difference in VAS score between the V4/EoT vs the V1 of the four treated arms. B Time course of VAS scores in different groups of participants (V1, V3, and V4/EoT included in the analysis). Statistically, differences were detected in NFX88 2.1 g/day and 4.2 g/day when time-comparisons were performed, whereas neither placebo nor NFX88 1.05 g/day participants reported any statistically difference. *p < 0.05. C Percentage of participants with a decrease in VAS ≥ 1.5 from V1 to V4/EoT. Note that participants treated with NFX88 2.1 g/day revealed higher pain relief in all analyses performed.

Fig. 6. VAS scores in participants with a high probability of having neuropathic component according to the PD-Q test at VS.

A Difference in VAS score between V4/EoT and V1 in the four treated groups. B Time course of the VAS scores in the different groups of participants with high neuropathic component (V1, V3, and V4/EoT included in the analysis). Statistically differences were detected in NFX88 2.1 g/day and 4.2 g/day when time comparisons were performed, whereas neither placebo nor NFX88 1.05 g/day participants reported any statistically difference. *p < 0.05. C. Percentage of participants with high neuropathic component that felt a decrease in VAS score ≥ 1.5, from V1 to V4/EoT.