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

NCT04516291

Last updated date
Study Location
L-MARC Research Center
Louisville, Kentucky, 40213, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Dyslipidemias, Hyperlipidemias, Hyperlipoproteinemias
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
40 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. Male or female participants aged ≥40 years at Screening.

2. Fasting non-HDL-C at Screening ≥100 mg/dL.

3. Fasting TG at Screening of 150 to 500 mg/dL, inclusive, which may be repeated once if deemed necessary.

4. 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.

5. Body weight ≥50 kg and ≤136 kg at Screening.

6. Capable of giving signed informed consent.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


1. Participant has active liver disease (other than NAFLD or NASH, which are permitted),
including chronic active hepatitis B or C or primary biliary cirrhosis.


2. 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.


3. Participant with a known bleeding diathesis or coagulation disorder.


4. 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

5. 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).


6. Presence of New York Heart Association Functional Classification IV heart failure
symptoms at Screening.


7. 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.


8. 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.


9. 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:


10. Prior treatment at any time with vupanorsen.


11. 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.


12. 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.


13. 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:


14. 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:


15. 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


16. Unstable weight (>5% shift in past month) or plan to start a diet for the purpose of
significant weight loss.


17. Hypersensitivity to the active substance or to any of the excipients or GalNAc.


18. Any major surgery, including bariatric surgery, within 3 months of Screening.


19. 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.


20. 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.


21. 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.

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Dyslipidemias, Hyperlipidemias, HyperlipoproteinemiasA Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70)
NCT04516291
  1. Louisville, Kentucky
  2. Louisville, Kentucky
  3. Raleigh, North Carolina
  4. Raleigh, North Carolina
  5. Dallas, Texas
  6. Dallas, Texas
  7. Brampton, Ontario
  8. Guelph, Ontario
  9. London, Ontario
  10. London, Ontario
  11. Mississauga, Ontario
  12. Chicoutimi, Quebec
  13. Chicoutimi, Quebec
  14. Mirabel, Quebec
  15. Pointe-Claire, Quebec
  16. Quebec,
  17. Quebec,
ALL GENDERS
40 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70)
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Dyslipidemias
  • Hyperlipidemias
  • Hyperlipoproteinemias
Intervention  ICMJE
  • Drug: Vupanorsen
    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.
    Other Name: PF-07285557
  • Drug: Placebo
    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 Arms  ICMJE
  • Placebo Comparator: Placebo
    No drug
    Intervention: Drug: Placebo
  • Experimental: Vupanorsen 80 mg every 4 weeks
    80 milligrams (mg) given subcutaneously every 4 weeks.
    Intervention: Drug: Vupanorsen
  • Experimental: Vupanorsen 60 mg every 2 weeks
    60 mg given subcutaneously every 2 weeks.
    Intervention: Drug: Vupanorsen
  • Experimental: Vupanorsen 120 mg every 4 weeks
    120 mg given subcutaneously every 4 weeks.
    Intervention: Drug: Vupanorsen
  • Experimental: Vupanorsen 80 mg every 2 weeks
    80 mg given subcutaneously every 2 weeks.
    Intervention: Drug: Vupanorsen
  • Experimental: Vupanorsen 160 mg every 4 weeks
    160 mg given subcutaneously every 4 weeks.
    Intervention: Drug: Vupanorsen
  • Experimental: Vupanorsen 120 mg every 2 weeks
    120 mg given subcutaneously every 2 weeks.
    Intervention: Drug: Vupanorsen
  • Experimental: Vupanorsen 160 mg every 2 weeks
    160 mg given subcutaneously every 2 weeks.
    Intervention: Drug: Vupanorsen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 13, 2020)
260
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 10, 2022
Estimated Primary Completion Date October 9, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participants aged ?40 years at Screening.
  2. Fasting non-HDL-C at Screening ?100 mg/dL.
  3. Fasting TG at Screening of 150 to 500 mg/dL, inclusive, which may be repeated once if deemed necessary.
  4. 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.
  5. Body weight ?50 kg and ?136 kg at Screening.
  6. Capable of giving signed informed consent.

Exclusion Criteria:

  1. Participant has active liver disease (other than NAFLD or NASH, which are permitted), including chronic active hepatitis B or C or primary biliary cirrhosis.
  2. 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.
  3. Participant with a known bleeding diathesis or coagulation disorder.
  4. 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
  5. 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).
  6. Presence of New York Heart Association Functional Classification IV heart failure symptoms at Screening.
  7. 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.
  8. 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.
  9. 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:

  10. Prior treatment at any time with vupanorsen.
  11. 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.
  12. 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.
  13. 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:

  14. 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:

  15. 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

  16. Unstable weight (>5% shift in past month) or plan to start a diet for the purpose of significant weight loss.
  17. Hypersensitivity to the active substance or to any of the excipients or GalNAc.
  18. Any major surgery, including bariatric surgery, within 3 months of Screening.
  19. 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.
  20. 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.
  21. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04516291
Other Study ID Numbers  ICMJE C4491011
2020-002796-35 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE TIMI Study Group
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP