sHTG Results | Trial Design

CORE and CORE2* pivotal trial study designs

TRYNGOLZA was evaluated in 2 identically designed, randomized, double-blind, placebo-controlled, phase 3 studies (CORE and CORE2*) that included a total of 1061 adults with sHTG1,2

Diagram showing the TRYNGOLZA study design stages.
  • In both studies, adult patients with severe hypertriglyceridemia (sHTG; N=1061) were randomized to receive TRYNGOLZA 50 mg, TRYNGOLZA 80 mg, or placebo once every 4 weeks for a 53-week treatment period1
  • >90% of patients who completed treatment rolled over to the sHTG open-label extension (OLE)6
  • Patients were eligible if they were ≥18 years of age and had severe hypertriglyceridemia.2 See below for CORE and CORE2 inclusion and exclusion criteria
KEY INCLUSION CRITERIA1

Fasting triglyceride levels ≥500 mg/dL

Participation in 4- to 8-week screening and qualification period that included at least 2 weeks of diet and lifestyle stabilization

Adherence to optimized, stable background lipid-lowering therapy prior to enrollment and throughout the study†

KEY EXCLUSION CRITERIA2

Genetically confirmed familial chylomicronemia syndrome

Acute pancreatitis at the time of screening or in the 4 weeks before screening

Poorly controlled diabetes mellitus (glycated hemoglobin level ≥9.5%)

Estimated glomerular filtration rate <30 mL per minute per 1.73 m2

*Trial 2 and Trial 3 in the full Prescribing Information.1
†Background lipid-lowering therapy in CORE and CORE2 primarily included statins (42% high-intensity; 27% moderate-intensity), fibrates (63%), and omega-3 fatty acids (32%).1
‡Including at least 2 weeks of diet and lifestyle stabilization.1
§Average of Weeks 25 and 27.1

TG=triglyceride. 

The efficacy of TRYNGOLZA was evaluated across multiple endpoints

Primary endpoint1
  • Mean percent change in fasting triglyceride levels from baseline to Month 6§ for both TRYNGOLZA 50 mg and 80 mg doses compared with placebo
Select secondary endpoints2,7
  • Mean percent change in fasting triglycerides from baseline to Month 12 compared with placebo
  • Adjudicated pancreatitis event rate in the pooled TRYNGOLZA group vs pooled placebo||
  • Mean percent changes from baseline compared with placebo in fasting lipids at Months 6 and 12:
    • apoC-III
    • Remnant cholesterol
    • Non–HDL-C
  • Proportion of pooled patients who achieved triglyceride levels <880 mg/dL and <500 mg/dL at Month 12
Select prespecified exploratory endpoints2,7
  • Proportion of pooled patients who achieved triglyceride levels <150 mg/dL at Month 12
  • Mean percent changes from baseline compared with placebo in fasting lipids at Months 6 and 12:
    • Total ApoB
    • ApoB-48 (a reliable marker of intestinal chylomicrons8)
    • HDL-C
    • LDL-C

||Pancreatitis events were assessed as a secondary endpoint in an integrated analysis of CORE and CORE2. Events were adjudicated by a blinded, independent committee according to the Revised Atlanta Diagnostic Criteria. Time to first event was compared between pooled TRYNGOLZA (50 mg and 80 mg) and pooled placebo using a log-rank test stratified by trial. Event rates over 53 weeks were compared between pooled TRYNGOLZA (50 mg and 80 mg) and pooled placebo using a negative binomial regression model.1
Among patients with baseline levels above those thresholds.2
Secondary outcomes were tested in hierarchical order for control of the overall type I error from multiple comparisons.2

apo=apolipoprotein; HDL-C=high-density lipoprotein cholesterol; LDL-C=low-density lipoprotein cholesterol.

  
 

Participant demographics and baseline characteristics were generally similar across treatment groups in CORE and CORE21

Pooled BASELINE characteristics1,2,9,10

23% had atherosclerotic cardiovascular disease

63% had type 2 diabetes mellitus

99% of patients were on background triglyceride-lowering therapies (~74% were on statins)

15% of patients had a history of pancreatitis within the prior 10 years

Mean (SD) and median fasting triglycerides at baseline were 1116 (990) mg/dL and 793 mg/dL, respectively

Average body mass index of ~31

16% were on a GLP-1#

Pooled demographics1

Mean age: 54 years

76% male

88% White

5% Asian

2% Black or African American

12% identified as Hispanic or Latino ethnicity

#15.9% of patients in CORE and 16.9% of patients in CORE2 were concomitantly receiving GLP-1s in the trials.9,10

GLP-1=glucagon-like peptide-1; SD=standard deviation.

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