Phase 2
Completed N=286
A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70)
Dyslipidemias · Hyperlipidemia · Hyperlipoproteinemias
Source: ClinicalTrials.gov NCT04516291 ↗
Enrolled (actual)
286
Serious AEs
6.6%
Results posted
Oct 2022
Primary outcomePrimary: Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 — -1.1; -23.5; -23.2; -25.3 Percent change — p=<0.001
Summary
This is a multicenter, Phase 2b, double-blind, placebo-controlled, parallel group study to provide data on efficacy, safety, tolerability, and pharmacokinetics (PK) of PF-07285557 (hereafter, vupanorsen) administered subcutaneously (SC) at various doses and regimens in participants with dyslipidemia, defined in this study as participants with elevated non-HDL-C and TG who are receiving a stable dose of a statin.
This study is also known as TaRgeting ANGPTL3 with an aNtiSense oLigonucleotide in AdulTs with dyslipidEmia (TRANSLATE-TIMI 70).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 |
-1.1; -23.5; -23.2; -25.3; -28.8; -27.8 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Triglyceride (TG), Apolipoprotein B (ApoB), Low-Density Lipoprotein-Cholesterol (LDL-C), and Non-HDL-C at Week 16 |
-2.53; -42.17; -44.71; -39.57; -49.21; -40.33 | — |
| SECONDARY Percent Change From Baseline in TG, ApoB, and LDL-C at Week 24 |
-1.8; -45.8; -45.6; -43.1; -52.3; -47.7 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 16 |
9.14; -51.12; -63.61; -58.19; -65.56; -60.35 | — |
| SECONDARY Percent Change From Baseline in ANGPTL3 at Week 24 |
13.3; -56.6; -66.3; -63.8; -73.0; -67.1 | <0.001 sig |
Eligibility Criteria
Inclusion Criteria
- Male or female participants aged ≥40 years at Screening.
- Fasting non-HDL-C at Screening ≥100 mg/dL.
- Fasting TG at Screening of 150 to 500 mg/dL, inclusive, which may be repeated once if deemed necessary.
- Participants must be on a stable dose of a statin for at least 1 month before Screening and plan to remain on the same medication and dose for the duration of the study.
- Body weight ≥50 kg and ≤136 kg at Screening.
- Capable of giving signed informed consent.
Exclusion Criteria
- Participant has active liver disease (other than NAFLD or NASH, which are permitted), including chronic active hepatitis B or C or primary biliary cirrhosis.
- Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg). Note: participants who are on an anti-hypertensive medication to treat hypertension should be on a stable dose at least 1 month prior to Screening. The investigator should ensure participant took anti-hypertensive medication as prescribed prior to evaluation of blood pressure.
- Participant with a known bleeding diathesis or coagulation disorder.
- Participants with ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the central laboratory and confirmed by a single repeat test, if deemed necessary: HbA1c ≥9.5% eGFR 2 × ULN Total bilirubin ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ULN Platelet count 5% shift in past month) or plan to start a diet for the purpose of significant weight loss.
- Hypersensitivity to the active substance or to any of the excipients or GalNAc.
- Any major surgery, including bariatric surgery, within 3 months of Screening.
- Participants with conditions contraindicated for MRI procedures including pacemakers or aneurysm clips; the presence of MRI incompatible implanted devices; metallic foreign bodies; metal tattoos (including permanent make-up); or severe claustrophobia impacting the ability to perform MRI. Participants who may require mild sedative or anxiolytic in order to complete the MRI may be enrolled.
- Participants unwilling or unable to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
- Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Data sourced from ClinicalTrials.gov (NCT04516291). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.