Journal of IiME Volume 4 Issue 1 www.investinme.org Ampligen® in Severely Debilitated CFS Patients (continued) CFS patients. The studies reviewed in this article examine the following: 1.) QT interval prolongation in CFS and increase in exercise tolerance, and 2.) interferon and cytokine levels in a Phase 3 clinical trial. QT Interval Prolongation in CFS and Increase in Exercise Tolerance Method: Data was analyzed from two well-controlled (double-blind, randomized, multi-center, placebocontrolled) studies, AMP-502 and AMP-516 (totaling >300 subjects), of poly(I) ·poly(C12,U). The purpose of this research was to determine the effect of treatment with rintatolimod on exercise tolerance and the use of concomitant medications, including medications known to prolong the QT interval. Summary of Results: In both studies, poly(I)·poly(C12,U) resulted in a statistically significant (p<0.05) increase in mobility and stamina (exercise tolerance) compared to placebo supported by patient responses to twice weekly dosing. The results from the two key studies are summarized in Table 1. Exercise treadmill testing (ETT) was the primary endpoint in the largest (n=234) placebo-controlled trial (AMP-516) and the proportions of subjects with changes from mean baseline ETT duration at Week 40 of at least 25% and 50% were 1.7-and 1.9 fold greater for the poly(I)·poly(C12,U) cohort than placebo, 39% vs. 23% and 26% vs. 14%, respectively (p<0.036). Of AMP-516 subjects, who took concomitant medications, 72% receiving poly(I)·poly(C12,U) decreased use of concomitant medications used to control the signs and symptoms of CFS versus 56% of subjects receiving placebo (p=0.015). An integrated analysis of efficacy shows that poly(I)·poly(C12,U) increases ETT and decreases the medications needed to suppress and control the symptoms of CFS. Voluntary use of concomitant medications significantly decreased in the poly(I)·poly(C12,U) group compared to the placebo arm in both studies (p<0.05). Many of these drugs used for symptomatic relief are known to prolong the QT interval. Drugs which prolong the QT interval are associated with an increased risk of Torsades de Pointes and sudden death. The list of drugs that prolong the QT Interval and/or induce TdP are shown in Table 2. An analysis of the QT interval in the Phase 3 study showed an increased risk of proarrhythmic potential in the placebo group compared to the poly(I)·poly(C12,U) treated group. Within the placebo group, patients who were prescribed one or more medications known to prolong the QT interval had a significant increase from their baseline QT interval. The use of concomitant medications (known to prolong the QT interval) used to alleviate symptoms of CFS was significantly decreased in the poly(I)·poly(C12,U) cohort. Patients randomized to receive poly(I)·poly(C12,U) were approximately three times more likely to have reduced exposure to medications known to prolong the QT interval, compared to patients randomized to receive placebo in AMP-502. Assessment of Interferon and Cytokine Levels Objective: To perform assessments of stored serum samples from CFS patients who participated in the AMP-516 study for markers of innate immune response (interferon and cytokine induction). The pretreatment interferon and cytokine levels, and the intra-patient changes from baseline, were also compared between the randomized groups to determine if Poly I : Poly C12U had a significant effect on serum levels. Table 1: Summary of ETT Efficacy Findings (Intent-to-Treat) from the WellControlled Trials Trial Time-to-Endpoint (Weeks) AMP-502 24 AMP-516 40 Invest in ME (Charity Nr. 1114035) Mean Change (Seconds) 95 96 p-value 0.010 0.047 Page 33/56
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