A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70)
- Conditions
- HyperlipidemiasDyslipidemiasHyperlipoproteinemias
- Interventions
- Drug: VupanorsenDrug: Placebo
- Registration Number
- NCT04516291
- Lead Sponsor
- Pfizer
- Brief 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).
- Detailed Description
This study is intended to enable selection of a dose(s) for future development of vupanorsen for cardiovascular (CV) risk reduction and hypertriglyceridemia.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 286
- 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.
-
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 <30 mL/min/1.73 m2 (as determined by the CKD-Epi equation) ALT or AST >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 <LLN
-
History of clinically significant acute cardiac event within 3 months before Screening (includes ischemic stroke, transient ischemic attack, myocardial infarction, revascularization procedures, hospitalization for heart failure).
-
Presence of New York Heart Association Functional Classification IV heart failure symptoms at Screening.
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Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
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Current history of alcoholism or drug addiction according to Diagnostic and Statistical Manual of Mental Disorders IV criteria within 12 months prior to Screening. Use of any recreational drugs within 12 months prior to Screening.
-
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
Prior/Concomitant Therapy:
-
Prior treatment at any time with vupanorsen.
-
Prior treatment with any oligonucleotide (including small interfering ribonucleic acid) within 6 months of Screening or prior treatment with inclisiran within 12 months of Screening.
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Use of TG lowering medication (eg, Vascepa [icosapent ethyl]), non-prescription dietary supplements (eg, fish oil) or other cholesterol lowering medication (eg, fibric acid derivatives, niacin, PCSK9 inhibitors, bile acid sequestrants, bempedoic acid) 30 days prior to Screening, other than statins and ezetimibe.
-
Use of warfarin or other coumarins, direct thrombin inhibitors, Factor Xa inhibitors, heparins or heparinoids 30 days prior to Screening.
Prior/Concurrent Clinical Study Experience:
-
Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
Diagnostic Assessments:
-
Participant has a clinically significant ECG abnormality during the Screening Period that requires further diagnostic evaluation or intervention (eg, new, clinically significant arrhythmia or a conduction disturbance).
Other Exclusions
-
Unstable weight (>5% shift in past month) or plan to start a diet for the purpose of significant weight loss.
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Hypersensitivity to the active substance or to any of the excipients or GalNAc.
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Any major surgery, including bariatric surgery, within 3 months of Screening.
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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.
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vupanorsen 160 mg every 4 weeks Vupanorsen 160 mg given subcutaneously every 4 weeks. Placebo Placebo No drug Vupanorsen 120 mg every 4 weeks Vupanorsen 120 mg given subcutaneously every 4 weeks. Vupanorsen 80 mg every 2 weeks Vupanorsen 80 mg given subcutaneously every 2 weeks. Vupanorsen 60 mg every 2 weeks Vupanorsen 60 mg given subcutaneously every 2 weeks. Vupanorsen 120 mg every 2 weeks Vupanorsen 120 mg given subcutaneously every 2 weeks. Vupanorsen 160 mg every 2 weeks Vupanorsen 160 mg given subcutaneously every 2 weeks. Vupanorsen 80 mg every 4 weeks Vupanorsen 80 milligrams (mg) given subcutaneously every 4 weeks.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 Baseline, Week 24 Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in TG, ApoB, and LDL-C at Week 24 Baseline, Week 24 Fasting was required for all lipid measures at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 16 Baseline, Week 16 ANGPTL3 is a protein primarily synthesized and secreted by the liver and is a member of the angiopoietin-like family of proteins. Blood samples were collected from participants in a fasted state for the measurement of ANGPTL3. Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
Percent Change From Baseline in ANGPTL3 at Week 24 Baseline, Week 24 ANGPTL3 is a protein primarily synthesized and secreted by the liver and is a member of the angiopoietin-like family of proteins. Blood samples were collected from participants in a fasted state for the measurement of ANGPTL3. Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
Percent Change From Baseline in Triglyceride (TG), Apolipoprotein B (ApoB), Low-Density Lipoprotein-Cholesterol (LDL-C), and Non-HDL-C at Week 16 Baseline, Week 16 Blood samples were collected from participants in a fasted state for the measurement of TG, ApoB, HDL-C and LDL-C. Fasting was required at least 10 hours before blood sample collection. Non-HDL-C was calculated as total cholesterol minus HDL cholesterol. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
Trial Locations
- Locations (112)
Horizon Clinical Research Associates, PLLC
🇺🇸Gilbert, Arizona, United States
GNMI MRI and CT Medical Imaging
🇨🇦Mississauga, Ontario, Canada
Aggarwal and Associates Limited
🇨🇦Brampton, Ontario, Canada
University Clinical Investigators, Inc.
🇺🇸Tustin, California, United States
Tower Radiology Parsons
🇺🇸Brandon, Florida, United States
Precision Imaging Centers
🇺🇸Jacksonville, Florida, United States
Advanced Research Institute, Inc.
🇺🇸New Port Richey, Florida, United States
Maryland Cardiovascular Specialists
🇺🇸Baltimore, Maryland, United States
Lahey Clinic Hospital and Medical Center
🇺🇸Burlington, Massachusetts, United States
Pentucket Medical Associates
🇺🇸Haverhill, Massachusetts, United States
Capital Cardiology Associates
🇺🇸Albany, New York, United States
ImageCare Latham
🇺🇸Latham, New York, United States
Wake Radiology Diagnostic Imaging Inc
🇺🇸Raleigh, North Carolina, United States
Clermont Radiology Orangeburg
🇺🇸Orangeburg, South Carolina, United States
South Carolina Clinical Research LLC
🇺🇸Orangeburg, South Carolina, United States
Tennessee Center for Clinical Trials
🇺🇸Tullahoma, Tennessee, United States
C-endo
🇨🇦Edmonton, Alberta, Canada
KMH Cardiology Centres Inc.
🇨🇦Kitchener, Ontario, Canada
Resonance Magnetique du Saguenay-Lac-Saint-Jean
🇨🇦Chicoutimi, Quebec, Canada
Ecogene-21
🇨🇦Chicoutimi, Quebec, Canada
Centrum Medyczne Enel-Med., Oddzial Alfa Plaza - Gdynia
🇵🇱Gdynia, Poland
Top Medical Lublin
🇵🇱Lublin, Poland
Centrum Zdrowia Metabolicznego Pawel Bogdanski
🇵🇱Poznan, Poland
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Perelman Center for Advanced Medicine, Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Medical Center Hospital
🇺🇸Odessa, Texas, United States
Hightop Medical Research Center
🇺🇸Cincinnati, Ohio, United States
Imaging Research Center-Cincinnati Children's
🇺🇸Cincinnati, Ohio, United States
SimonMed Houston
🇺🇸Houston, Texas, United States
J. Lewis Research, Inc. / Foothill Family Clinic South
🇺🇸Salt Lake City, Utah, United States
Southwest Clinical Trials
🇺🇸Houston, Texas, United States
Regions Hospital - HealthPartners
🇺🇸Saint Paul, Minnesota, United States
Clinical Trials Research
🇺🇸Lincoln, California, United States
West Coast Radiology
🇺🇸Santa Ana, California, United States
Susan B. Allen Memorial Hospital
🇺🇸El Dorado, Kansas, United States
Alliance for Multispecialty Research, LLC
🇺🇸El Dorado, Kansas, United States
Randolph Health Internal Medicine
🇺🇸Asheboro, North Carolina, United States
Randolph Health MRI Center
🇺🇸Asheboro, North Carolina, United States
PMG Research of Raleigh, LLC d/b/a PMG Research of Cary
🇺🇸Cary, North Carolina, United States
Wake Radiology
🇺🇸Cary, North Carolina, United States
Accellacare - Raleigh
🇺🇸Raleigh, North Carolina, United States
PMG Research of Raleigh, LLC
🇺🇸Raleigh, North Carolina, United States
Tullahoma HMA, LLC d\b\a Tennova HealthCare Harton
🇺🇸Tullahoma, Tennessee, United States
Dallas Diabetes Research Center
🇺🇸Dallas, Texas, United States
Southwest Diagnostic Imaging Center
🇺🇸Dallas, Texas, United States
Permian Research Foundation
🇺🇸Odessa, Texas, United States
National Clinical Research, Inc.
🇺🇸Richmond, Virginia, United States
Bellevue Medical Imaging
🇺🇸Seattle, Washington, United States
Rainier Clinical Research Center
🇺🇸Renton, Washington, United States
Universal Research Group, LLC
🇺🇸Tacoma, Washington, United States
MIC Medical Imaging
🇨🇦Edmonton, Alberta, Canada
Synergy Medical Clinic
🇨🇦Sherwood Park, Alberta, Canada
SMH Cardiology Clinical Trials Inc.
🇨🇦Surrey, British Columbia, Canada
Nova Scotia Health Authority QE II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
GNMI Medical Imaging
🇨🇦Mississauga, Ontario, Canada
Holland Bloorview Kids Rehabilitation Hospital
🇨🇦Toronto, Ontario, Canada
Dr. Anil K. Gupta Medicine Professional Corporation
🇨🇦Toronto, Ontario, Canada
Manna Research (Mirabel)
🇨🇦Mirabel, Quebec, Canada
Research Institute of the McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Centre de Recherche Saint-Louis
🇨🇦Quebec, Canada
IRM Quebec Synase
🇨🇦Quebec, Canada
IRM Quebec - Complexe Synase
🇨🇦Quebec, Canada
Diex Recherche Quebec Inc.
🇨🇦Quebec, Canada
NZOZ Kendron
🇵🇱Bialystok, Poland
Kardio Brynow
🇵🇱Katowice, Poland
Malopolskie Centrum Sercowo-Naczyniowe PAKS - Chrzanow
🇵🇱Chrzanow, Poland
Niepubliczny Zaklad Opieki Zdrowotnej "TERAPIA OPTIMA"
🇵🇱Katowice, Poland
HELIMED Katowice - Rezonans Magnetyczny, Tomografia Komputerowa
🇵🇱Katowice, Poland
SZPITAL SW. ELZBIETY W KATOWICACH Polsko-Amerykanskie Kliniki Serca
🇵🇱Tychy, Poland
Wro Medica
🇵🇱Wroclaw, Poland
Skanmex (MRI)
🇵🇱Wroclaw, Poland
TOMMA Pracownia rezonansu magnetycznego we Wroclawiu
🇵🇱Wroclaw, Poland
Diagnostic Radiological Imaging
🇺🇸Sacramento, California, United States
Sand Lakes Imaging
🇺🇸Orlando, Florida, United States
L-MARC Research Center
🇺🇸Louisville, Kentucky, United States
Heartland Imaging
🇺🇸Louisville, Kentucky, United States
PMG Research of Winston-Salem, LLC
🇺🇸Winston-Salem, North Carolina, United States
Radimed West Island
🇨🇦Pointe-Claire, Quebec, Canada
LMC Clinical Research Inc. (Thornhill)
🇨🇦Concord, Ontario, Canada
HELIMED Katowice - Rezonans Magnetyczny, Tomografia Komputerowa (MRI)
🇵🇱Katowice, Poland
Innovative Research of West Florida, Inc.
🇺🇸Clearwater, Florida, United States
Borland-Groover Clinic
🇺🇸Jacksonville, Florida, United States
Care Partners Clinical Research, LLC
🇺🇸Jacksonville, Florida, United States
LMC Clinical Research Inc. (Barrie)
🇨🇦Barrie, Ontario, Canada
LMC Clinical Research Inc. (Etobicoke)
🇨🇦Etobicoke, Ontario, Canada
Dawson Clinical Research
🇨🇦Guelph, Ontario, Canada
Scottsdale Medical Imaging Research, LLC
🇺🇸Gilbert, Arizona, United States
Seton Imaging Center
🇺🇸Baltimore, Maryland, United States
Recherche GCP Research
🇨🇦Montreal, Quebec, Canada
Montreal Heart Institute
🇨🇦Montreal, Quebec, Canada
Diex Recherche Joliette
🇨🇦St-Charles-Borromee, Quebec, Canada
Futuremeds
🇵🇱Wroclaw, Poland
Atria Clinical Research
🇺🇸Little Rock, Arkansas, United States
Westside Center for Clinical Research
🇺🇸Jacksonville, Florida, United States
Milestone Research Inc.
🇨🇦London, Ontario, Canada
North York Diagnostic and Cardiac Centre
🇨🇦North York, Ontario, Canada
Devonshire Clinical Research Inc.
🇨🇦Woodstock, Ontario, Canada
Centrum Badan Klinicznych PI-House sp. z o.o.
🇵🇱Gdansk, Poland
"TWOJA PRZYCHODNIA" Sp. z o.o.
🇵🇱Lublin, Poland
Viable Research Management LLC
🇺🇸Henderson, Nevada, United States
Tower Radiology
🇺🇸Brandon, Florida, United States
Clinical Research of Central Florida
🇺🇸Winter Haven, Florida, United States
Research Institute of the McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Alpha Recherche Clinique
🇨🇦Quebec, Canada
ClinicMed Daniluk, Nowak Spolka Jawna
🇵🇱Bialystok, Poland
Arterieart Sp. z o.o.
🇵🇱Puszczykowo, Poland
Pueblo Medical Imaging
🇺🇸Henderson, Nevada, United States
Robarts Research Institute, Western University
🇨🇦London, Ontario, Canada
St Johns Center for Clinical Research
🇺🇸Saint Augustine, Florida, United States
Access MRI
🇨🇦Surrey, British Columbia, Canada
Bluewater Clinical Research Group Inc.
🇨🇦Sarnia, Ontario, Canada
CARTI
🇺🇸Little Rock, Arkansas, United States