A phase 2a open-label clinical trial to determine the effect of famciclovir on EBV activity as measured by EBV shedding in the saliva of patients with multiple sclerosis

一项 2a 期开放标签临床试验,旨在确定泛昔洛韦对多发性硬化症患者唾液中 EBV 脱落量测量的 EBV 活性的影响

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作者:Ruth Dobson, David Holden, Nicola Vickaryous, Jonathan Bestwick, Katila George, Tatiana Sayali, Lucia Bianchi, Mohammad Wafa, Julian Gold, Gavin Giovannoni

Background

Despite increasing evidence that Epstein-Barr virus (EBV) plays a causal role in MS, no treatments have been shown to reduce EBV turnover. We studied the effect of famciclovir on salivary EBV shedding in people with MS (NCT05283551) in a pilot, proof-of-concept study.

Conclusion

No significant effect of famciclovir on EBV shedding was seen in this small pilot study. Given the low numbers, a small effect of famciclovir cannot be excluded. Salivary EBV shedding in this natalizumab-treated cohort was lower than in previous studies, which requires replication.

Methods

People with MS receiving natalizumab provided weekly saliva samples for 12 weeks before starting famciclovir 500 mg twice daily for 12 weeks. Twelve saliva samples were provided on treatment and 12 following treatment. A real-time qPCR Taqman assay was used to detect EBV DNA in saliva. The proportion of saliva samples containing EBV DNA was compared using the Friedman test.

Results

Of 30 participants (19 F; mean age 41 years; median EDSS 3.5), 29 received famciclovir, and 24 completed the 12-week course. Twenty-one participants provided at least one usable saliva sample in all epochs. Ten of the 21 had shedding in at least one sample pre-drug; 7/21 when taking famciclovir (not significant). No difference in EBV DNA copy number was seen. There were no drug-related serious adverse events.

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