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DyslipidemiasPhase 2NCT04516291

A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70)

A Phase 2 study testing Vupanorsen in people with Dyslipidemias and Hyperlipidemias, run by Pfizer at 114 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 40 years and older
What is being tested?
Vupanorsen
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
286 participants
Where
114 sitesin 3 countries
Study dates
28 Sep 2020to 6 Dec 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.
  • 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.
  • 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.
  • 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.

Trial locations and contacts

114 sites in 3 countries.

114 sites in 3 countries

United States59 sites

  • Capital Cardiology Associates

    Albany, New York, 12211

  • Randolph Health Internal Medicine

    Asheboro, North Carolina, 27203

  • Randolph Health MRI Center

    Asheboro, North Carolina, 27205

  • Maryland Cardiovascular Specialists

    Baltimore, Maryland, 21229

  • Seton Imaging Center

    Baltimore, Maryland, 21229

  • Tower Radiology Parsons

    Brandon, Florida, 33511

  • Tower Radiology

    Brandon, Florida, 33511

  • Lahey Clinic Hospital and Medical Center

    Burlington, Massachusetts, 01805

  • PMG Research of Raleigh, LLC d/b/a PMG Research of Cary

    Cary, North Carolina, 27518

  • Wake Radiology

    Cary, North Carolina, 27518

  • Hightop Medical Research Center

    Cincinnati, Ohio, 45224

  • Imaging Research Center-Cincinnati Children's

    Cincinnati, Ohio, 45229

  • Innovative Research of West Florida, Inc.

    Clearwater, Florida, 33756

  • Dallas Diabetes Research Center

    Dallas, Texas, 75230

  • Southwest Diagnostic Imaging Center

    Dallas, Texas, 75231

  • Alliance for Multispecialty Research, LLC

    El Dorado, Kansas, 67042

  • Susan B. Allen Memorial Hospital

    El Dorado, Kansas, 67042

  • Horizon Clinical Research Associates, PLLC

    Gilbert, Arizona, 85295

  • Scottsdale Medical Imaging Research, LLC

    Gilbert, Arizona, 85297

  • Pentucket Medical Associates

    Haverhill, Massachusetts, 01830

  • Viable Research Management LLC

    Henderson, Nevada, 89014

  • Pueblo Medical Imaging

    Henderson, Nevada, 89074

  • SimonMed Houston

    Houston, Texas, 77030

  • Southwest Clinical Trials

    Houston, Texas, 77074

  • Westside Center for Clinical Research

    Jacksonville, Florida, 32205

  • Borland-Groover Clinic

    Jacksonville, Florida, 32256

  • Precision Imaging Centers

    Jacksonville, Florida, 32256

  • Care Partners Clinical Research, LLC

    Jacksonville, Florida, 32277

  • ImageCare Latham

    Latham, New York, 12110

  • Clinical Trials Research

    Lincoln, California, 95648

  • CARTI

    Little Rock, Arkansas, 72205

  • Atria Clinical Research

    Little Rock, Arkansas, 72209

  • L-MARC Research Center

    Louisville, Kentucky, 40213

  • Heartland Imaging

    Louisville, Kentucky, 40222

  • Advanced Research Institute, Inc.

    New Port Richey, Florida, 34653

  • Medical Center Hospital

    Odessa, Texas, 79761

  • Permian Research Foundation

    Odessa, Texas, 79761

  • Clermont Radiology Orangeburg

    Orangeburg, South Carolina, 29118

  • South Carolina Clinical Research LLC

    Orangeburg, South Carolina, 29118

  • Sand Lakes Imaging

    Orlando, Florida, 32819

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Perelman Center for Advanced Medicine, Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Accellacare - Raleigh

    Raleigh, North Carolina, 27609

  • PMG Research of Raleigh, LLC

    Raleigh, North Carolina, 27609

  • Wake Radiology Diagnostic Imaging Inc

    Raleigh, North Carolina, 27609

  • Rainier Clinical Research Center

    Renton, Washington, 98057

  • National Clinical Research, Inc.

    Richmond, Virginia, 23294

  • Diagnostic Radiological Imaging

    Sacramento, California, 95825

  • St Johns Center for Clinical Research

    Saint Augustine, Florida, 32086

  • Regions Hospital - HealthPartners

    Saint Paul, Minnesota, 55101

  • J. Lewis Research, Inc. / Foothill Family Clinic South

    Salt Lake City, Utah, 84121

  • West Coast Radiology

    Santa Ana, California, 92705

  • Bellevue Medical Imaging

    Seattle, Washington, 98166

  • Universal Research Group, LLC

    Tacoma, Washington, 98405

  • Tennessee Center for Clinical Trials

    Tullahoma, Tennessee, 37388

  • Tullahoma HMA, LLC d\b\a Tennova HealthCare Harton

    Tullahoma, Tennessee, 37388

  • University Clinical Investigators, Inc.

    Tustin, California, 92780

  • PMG Research of Winston-Salem, LLC

    Winston-Salem, North Carolina, 27103

  • Clinical Research of Central Florida

    Winter Haven, Florida, 33880

Other trials in United States

Canada37 sites

  • LMC Clinical Research Inc. (Barrie)

    Barrie, Ontario, L4N 7L3

  • Aggarwal and Associates Limited

    Brampton, Ontario, L6T 0G1

  • Resonance Magnetique du Saguenay-Lac-Saint-Jean

    Chicoutimi, Quebec, G7H 4J1

  • Ecogene-21

    Chicoutimi, Quebec, G7H 7K9

  • LMC Clinical Research Inc. (Thornhill)

    Concord, Ontario, L4K 4M2

  • C-endo

    Edmonton, Alberta, T6H 2L4

  • MIC Medical Imaging

    Edmonton, Alberta, T6J 5E5

  • LMC Clinical Research Inc. (Etobicoke)

    Etobicoke, Ontario, M9R 4E1

  • Dawson Clinical Research

    Guelph, Ontario, N1H 1B1

  • Nova Scotia Health Authority QE II Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

  • Nova Scotia Health Authority QE II Health Sciences Centre

    Halifax, Nova Scotia, B3H 2Y9

  • KMH Cardiology Centres Inc.

    Kitchener, Ontario, N2M 5N4

  • Milestone Research Inc.

    London, Ontario, N5W 6A2

  • Robarts Research Institute, Western University

    London, Ontario, N6A 5B7

  • Manna Research (Mirabel)

    Mirabel, Quebec, J7J 2K8

  • GNMI Medical Imaging

    Mississauga, Ontario, L5R 3K6

  • GNMI Medical Imaging

    Mississauga, Ontario, L5R 3K7

  • GNMI MRI and CT Medical Imaging

    Mississauga, Ontario, L6R 3K7

  • Recherche GCP Research

    Montreal, Quebec, H1M 1B1

  • Montreal Heart Institute

    Montreal, Quebec, H1T 1C8

  • Research Institute of the McGill University Health Center

    Montreal, Quebec, H4A 3J1

  • Research Institute of the McGill University Health Centre

    Montreal, Quebec, H4A 3J1

  • North York Diagnostic and Cardiac Centre

    North York, Ontario, M6B 3H7

  • Radimed West Island

    Pointe-Claire, Quebec, H9R 4R9

  • IRM Quebec - Complexe Synase

    Québec, G1J 0H4

  • IRM Quebec Synase

    Québec, G1J 0H4

  • Diex Recherche Quebec Inc.

    Québec, G1N 4V3

  • Centre de Recherche Saint-Louis

    Québec, G1W4R4

  • Alpha Recherche Clinique

    Québec, G2J 0C4

  • Diex Recherche Joliette

    Saint-Charles-Borromée, Quebec, J6E 2B4

  • Bluewater Clinical Research Group Inc.

    Sarnia, Ontario, N7T 4X3

  • Synergy Medical Clinic

    Sherwood Park, Alberta, T8H 0N2

  • Access MRI

    Surrey, British Columbia, V3S 9A5

  • SMH Cardiology Clinical Trials Inc.

    Surrey, British Columbia, V3V 0C6

  • Holland Bloorview Kids Rehabilitation Hospital

    Toronto, Ontario, M4G 1R8

  • Dr. Anil K. Gupta Medicine Professional Corporation

    Toronto, Ontario, M9V 4B4

  • Devonshire Clinical Research Inc.

    Woodstock, Ontario, N4S 5P5

Other trials in Canada

Poland18 sites

  • NZOZ Kendron

    Bialystok, 15-402

  • ClinicMed Daniluk, Nowak Spolka Jawna

    Bialystok, 15-879

  • Malopolskie Centrum Sercowo-Naczyniowe PAKS - Chrzanow

    Chrzanów, 32-500

  • Centrum Badan Klinicznych PI-House sp. z o.o.

    Gdansk, 80-546

  • Centrum Medyczne Enel-Med., Oddzial Alfa Plaza - Gdynia

    Gdynia, 81-366

  • Kardio Brynow

    Katowice, 40-555

  • Niepubliczny Zaklad Opieki Zdrowotnej "TERAPIA OPTIMA"

    Katowice, 40-752

  • HELIMED Katowice - Rezonans Magnetyczny, Tomografia Komputerowa (MRI)

    Katowice, 40-760

  • HELIMED Katowice - Rezonans Magnetyczny, Tomografia Komputerowa

    Katowice, 40-760

  • "TWOJA PRZYCHODNIA" Sp. z o.o.

    Lublin, 20-857

  • Top Medical Lublin

    Lublin, 20-883

  • Centrum Zdrowia Metabolicznego Pawel Bogdanski

    Poznan, 60-589

  • Arterieart Sp. z o.o.

    Puszczykowo, 62-041

  • SZPITAL SW. ELZBIETY W KATOWICACH Polsko-Amerykanskie Kliniki Serca

    Tychy, 43-100

  • Futuremeds

    Wroclaw, 50-088

  • Skanmex (MRI)

    Wroclaw, 50-450

  • Wro Medica

    Wroclaw, 51-685

  • TOMMA Pracownia rezonansu magnetycznego we Wroclawiu

    Wroclaw, 53-234

Other trials in Poland

About this study

Official title: A Phase 2b Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Ranging Study to Assess the Efficacy, Safety, and Tolerability of Vupanorsen (PF-07285557) in Statin-Treated Participants With Dyslipidemia

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).

Read the 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.

Being tested
Vupanorsen, Placebo
Keywords
Primary hyperlipidemia, Mixed dyslipidemia, Lipid Metabolism Disorders, Metabolic Diseases
Medical subject headings
Dyslipidemias, Hyperlipidemias, Hyperlipoproteinemias, Lipid Metabolism Disorders, Metabolic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VupanorsenDrug

    Also called PF-07285557

    Vupanorsen and placebo will be provided as prefilled syringes packaged and dispensed in cartons with tamper-evident seals. Only single-use syringes will be used.

  • PlaceboDrug

    Vupanorsen and placebo will be provided as prefilled syringes packaged and dispensed in cartons with tamper-evident seals. Only single-use syringes will be used.

Study groups in NCT04516291
Study groupRoleWhat they receive
PlaceboPlacebo comparatorNo drug
Receives: Drug: Placebo
Vupanorsen 80 mg every 4 weeksExperimental80 milligrams (mg) given subcutaneously every 4 weeks.
Receives: Drug: Vupanorsen
Vupanorsen 60 mg every 2 weeksExperimental60 mg given subcutaneously every 2 weeks.
Receives: Drug: Vupanorsen
Vupanorsen 120 mg every 4 weeksExperimental120 mg given subcutaneously every 4 weeks.
Receives: Drug: Vupanorsen
Vupanorsen 80 mg every 2 weeksExperimental80 mg given subcutaneously every 2 weeks.
Receives: Drug: Vupanorsen
Vupanorsen 160 mg every 4 weeksExperimental160 mg given subcutaneously every 4 weeks.
Receives: Drug: Vupanorsen
Vupanorsen 120 mg every 2 weeksExperimental120 mg given subcutaneously every 2 weeks.
Receives: Drug: Vupanorsen
Vupanorsen 160 mg every 2 weeksExperimental160 mg given subcutaneously every 2 weeks.
Receives: Drug: Vupanorsen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at 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.

    Measured: Baseline, Week 24

Secondary outcomes (4)

  1. Percent Change From Baseline in Triglyceride (TG), Apolipoprotein B (ApoB), Low-Density Lipoprotein-Cholesterol (LDL-C), and Non-HDL-C at 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.

    Measured: Baseline, Week 16

  2. Percent Change From Baseline in TG, ApoB, and LDL-C at 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.

    Measured: Baseline, Week 24

  3. Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at 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.

    Measured: Baseline, Week 16

  4. Percent Change From Baseline in ANGPTL3 at 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.

    Measured: Baseline, Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Aug 2020
  2. Study start28 Sep 2020
  3. Primary completion29 Sep 2021
  4. Study completion6 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
286 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04516291
Sponsor's protocol ID
C4491011
Other IDs
2020-002796-35
Status last verified
Sep 2022
First submitted
13 Aug 2020
Last updated
4 Oct 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

  • Bergmark BA, Marston NA, Bramson CR, Curto M, Ramos V, Jevne A, Kuder JF, Park JG, Murphy SA, Verma S, Wojakowski W, Terra SG, Sabatine MS, Wiviott SD; TRANSLATE-TIMI 70 Investigators. Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70. Circulation. 2022 May 3;145(18):1377-1386. doi: 10.1161/CIRCULATIONAHA.122.059266. Epub 2022 Apr 3.

    PubMed 35369705

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vupanorsen in people with Dyslipidemias and Hyperlipidemias, run by Pfizer at 114 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 114 sites in United States, Canada, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 (time frame: Baseline, Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04516291, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2022.

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