Completed Clinical Trials

Phase 2 ASSERT Clinical Trial

Resverlogix successfully completed the Phase 2 "ASSERT" Clinical Trial led by the Cleveland Clinic. The ASSERT trial was a randomized, double-blind, placebo-controlled, multi-centered US study which enrolled 299 patients with stable coronary artery disease for a period of 13 weeks.

The ASSERT trial data demonstrated that the three key biomarkers in the reverse cholesterol transport (RCT) process showed dose dependent and consistent improvement. The trial showed dose dependent increases in ApoA-l, statistically significant increases in HDL cholesterol including alpha1 particles or functional HDL, and highly statistically significant increases in large HDL particles. RCT is a pathway by which accumulated cholesterol is transported from the arterial wall to the liver for excretion, thus reducing and/or preventing atherosclerosis.

Across all patients, in the high dose, ApoA-I achieved a 5.6% increase with a statistical value of p=0.06. The overall ApoA-I biomarker showed a dose trending statistical significance of p=0.035. Data presented also showed that the ApoA-I and other HDL particles continued to be increasing at the end of the 12 week study. Both the 8.3% HDL cholesterol increase and the 21.1% large particle HDL increase were highly statistically significant, p<0.01 and p<0.001 respectively.

In a post-hoc analysis patients who received the newer class of statins and who had baseline HDL below 45mg/dL, an important high-risk subpopulation, the middle dose of 200 mg saw the most pronounced increases of 12% in ApoA-I (p<0.002), 21% in HDL cholesterol (p<0.015) and 32% in large particle HDL (p<0.018).

Phase 1b/2a Clinical Trial

The Phase 1b/2a study tested RVX-208 for 28 days in three different dosing arms: a low dose arm with 24 subjects, a dose-escalation arm with 24 subjects, and a third high dose arm with 24 subjects. The trial was a double blind safety and tolerance study investigated the pharmacokinetics and also early pharmacodynamics effects of RVX-208. This trial also examined early markers for reverse cholesterol transport such as ApoA-l, HDL-c, pre-beta HDL and alpha HDL subparticles. Approximately half of the subjects had low levels of baseline HDL cholesterol.

Results concluded that the Phase 1b/2a showed that RVX-208, is safe and tolerable. Most importantly RVX-208 has met its primary endpoint to increase the production of plasma ApoA-I, the key cardioprotective protein in high-density lipoprotein (HDL), often referred to as “good” cholesterol. ApoA-I is generally endorsed as a key protective factor against atherosclerosis and cardiovascular disease with 40% of all first heart attack patients having low ApoA-I.

Highlights from the study are as follows:

  • The primary endpoint, plasma ApoA-I increase compared to placebo, achieved a range in all subjects of 5.1% - 10.4% in all doses at days 8 and 28 respectively.
  • At the lowest dose of 1mg/kg b.i.d. in subjects with low levels of HDL-c, plasma ApoA-l increases reached statistical significance of 5.7% (p<0.05) at day 8 and 7.8% (p<0.05) at day 28.
  • A critical RCT functionality marker, alpha-1 HDL particles, illustrated highly statistical significance with an increase of 46.7% (p<0.004), in all subjects and 57.2% (p<0.02) in the low dose arm over placebo at day 28.
  • Pharmacokinetic parameters of RVX-208 were dose dependant with oral administration.
  • RVX-208 was shown to be compatible with simvastatin (40mg).
  • Seventy out of seventy two subjects completed the trial. One subject did not complete the trial due to personal reasons and one other subject did not complete the trial due to a serious adverse event, cholecystitis (gall stones), which was judged not related to the study drug.

The primary objectives of the Phase 1a trial were to examine the safety, tolerability and pharmacokinetics of RVX-208. This study successfully met those objectives. Analysis from 24 healthy volunteers in the 7 day RVX-208 trial showed statistically significant improvements over placebo in key variables assessed.

Phase 1a Clinical Trial

Highlights of the study include:

  • Increases in pre-beta HDL of in excess of 30%, cholesterol efflux above 10%, serum ApoAl above 10%, and HDL-C above 10% (not statistically significant) versus placebo.

This follows a very similar improvement pattern as previously demonstrated by Resverlogix in the African Green Monkey studies. Crucial to these findings is the rapid onset of action in this 7 day trial, with the serum ApoA-I increases surpassing the previous 8% five week (35 day) average benchmark totals displayed by Pfizer’s previous ApoA-I Milano recombinant protein studies.