A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist Rintatolimod [Ampligen®] in severe cases of Chronic Fatigue Syndrome
– Source: PloS One, Mar 14, 2012
By David R Strayer, Daniel L Peterson, et al.
[Note: To read the full text of this landmark open access article free, click HERE and download the PDF. Rintatolimod (aka Ampligen) was designated an “Orphan Drug” for CFS by the FDA, for the purpose of this trial.]
Background: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a severely debilitating disease of unknown pathogenesis consisting of a variety of symptoms including severe fatigue.
The objective of the study was to examine the efficacy and safety of a TLR-3 agonist, rintatolimod (Poly I: C12U), in patients with debilitating CFS/ME.
Methods and Findings: A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites.
The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET).
Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS), Activities of Daily Living (ADL), and Vitality Score (SF 36).
Subjects receiving rintatolimod [Ampligen] for 40 weeks improved intra-patient placebo-adjusted exercise tolerance 21.3% (p = 0.047) from baseline in an intention-to-treat analysis.
Correction for subjects with reduced dosing compliance increased placebo-adjusted exercise tolerance improvement to 28% (p = 0.022).
• The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies.
• The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048).
• Placebo subjects crossed-over to receive rintatolimod [Ampligen] demonstrated an intra-patient improvement in exercise tolerance performance at 24 weeks of 39% (p = 0.04). Rintatolimod at 400 mg twice weekly was generally well-tolerated.
Conclusions/Significance: Rintatolimod [Ampligen] produced objective improvement in exercise tolerance and a reduction in CFS/ME related concomitant medication usage as well as other secondary outcomes.
Trial Registration: ClinicalTrials.gov NCT00215800
Source: PloS One, Mar 14, 2012. Strayer DR, Carter WA, Stouch BC, Stevens SR, Bateman L, Cimoch PJ, Lapp CW, Peterson DL, Chronic Fatigue Syndrome AMP-516 Study Group, Mitchell WM. Hemispherx Biopharma, Inc., Philadelphia, Pennsylvania; BCS Consulting, Philadelphia; University of the Pacific, Stockton, California; Fatigue Consultation Clinic, Salt Lake City, Utah; Center for Special Immunology, Fountain Valley, California; Hunter-Hopkins Center, Charlotte, North Carolina; Sierra Internal Medicine Associates, Incline Village, Nevada; Vanderbilt University School of Medicine, Nashville, Tennessee, USA.