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History of Changes for Study: NCT04516291
A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70)
Latest version (submitted September 6, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 13, 2020 None (earliest Version on record)
2 September 29, 2020 Recruitment Status, Study Status, IPDSharing, Contacts/Locations and Oversight
3 October 23, 2020 Contacts/Locations and Study Status
4 November 2, 2020 Contacts/Locations and Study Status
5 November 16, 2020 Contacts/Locations and Study Status
6 November 19, 2020 Contacts/Locations and Study Status
7 December 15, 2020 Contacts/Locations and Study Status
8 January 11, 2021 Contacts/Locations and Study Status
9 February 9, 2021 Contacts/Locations and Study Status
10 March 4, 2021 Contacts/Locations and Study Status
11 March 8, 2021 Contacts/Locations and Study Status
12 March 10, 2021 Contacts/Locations and Study Status
13 March 17, 2021 Contacts/Locations and Study Status
14 April 2, 2021 Contacts/Locations and Study Status
15 April 20, 2021 Study Status and Contacts/Locations
16 May 19, 2021 Recruitment Status, Study Status and Contacts/Locations
17 June 8, 2021 Study Design and Study Status
18 July 28, 2021 Contacts/Locations and Study Status
19 October 5, 2021 Study Status and Contacts/Locations
20 January 6, 2022 Recruitment Status and Study Status
21 September 6, 2022 Outcome Measures, Study Status, Contacts/Locations, Document Section, Results and IPDSharing
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Study NCT04516291
Submitted Date:  August 13, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: C4491011
Brief Title: A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70)
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
Secondary IDs: 2020-002796-35 [EudraCT Number]
Open or close this module Study Status
Record Verification: August 2020
Overall Status: Not yet recruiting
Study Start: September 28, 2020
Primary Completion: October 9, 2021 [Anticipated]
Study Completion: January 10, 2022 [Anticipated]
First Submitted: August 13, 2020
First Submitted that
Met QC Criteria:
August 13, 2020
First Posted: August 18, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
August 13, 2020
Last Update Posted: August 18, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Pfizer
Responsible Party: Sponsor
Collaborators: TIMI Study Group
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.
Open or close this module Conditions
Conditions: Dyslipidemias
Hyperlipidemias
Hyperlipoproteinemias
Keywords: Primary hyperlipidemia
Mixed dyslipidemia
Lipid Metabolism Disorders
Metabolic Diseases
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 8
Masking: Triple (Participant, Care Provider, Investigator)
Allocation: Randomized
Enrollment: 260 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Placebo Comparator: Placebo
No drug
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.
Experimental: Vupanorsen 80 mg every 4 weeks
80 milligrams (mg) given subcutaneously every 4 weeks.
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 Names:
  • PF-07285557
Experimental: Vupanorsen 60 mg every 2 weeks
60 mg given subcutaneously every 2 weeks.
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 Names:
  • PF-07285557
Experimental: Vupanorsen 120 mg every 4 weeks
120 mg given subcutaneously every 4 weeks.
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 Names:
  • PF-07285557
Experimental: Vupanorsen 80 mg every 2 weeks
80 mg given subcutaneously every 2 weeks.
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 Names:
  • PF-07285557
Experimental: Vupanorsen 160 mg every 4 weeks
160 mg given subcutaneously every 4 weeks.
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 Names:
  • PF-07285557
Experimental: Vupanorsen 120 mg every 2 weeks
120 mg given subcutaneously every 2 weeks.
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 Names:
  • PF-07285557
Experimental: Vupanorsen 160 mg every 2 weeks
160 mg given subcutaneously every 2 weeks.
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 Names:
  • PF-07285557
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Percent Change from Baseline in Non High Density Lipoprotein Cholesterol at Week 24
[ Time Frame: baseline, Week 24 ]

Secondary Outcome Measures:
1. Percent change from Baseline in Fasting Non High Density Lipoprotein Cholesterol at Week 16
[ Time Frame: baseline, Week 16 ]

2. Percent change from baseline in angiopoietin-like protein 3 (ANGPTL3) at Week 16 and Week 24
[ Time Frame: baseline, Week 16, Week 24 ]

3. Percent Change from Baseline in low density lipoprotein at Week 16 and Week 24
[ Time Frame: baseline, Week 16, Week 24 ]

4. Percent Change from Baseline in apolipoprotein B at Week 16 and Week 24
[ Time Frame: baseline, Week 16, Week 24 ]

5. Percent change from Baseline in triglycerides at Week 16 and Week 24
[ Time Frame: baseline, Week 16, Week 24 ]

Open or close this module Eligibility
Minimum Age: 40 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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.
Open or close this module Contacts/Locations
Central Contact Person: Pfizer CT.gov Call Center
Telephone: 1-800-718-1021
Email: ClinicalTrials.gov_Inquiries@pfizer.com
Study Officials: Pfizer CT.gov Call Center
Study Director
Pfizer
Locations:
Open or close this module IPDSharing
Plan to Share IPD: 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
Supporting Information:
Time Frame:
Access Criteria:
URL:
Open or close this module References
Links: Description: To obtain contact information for a study center near you, click here.
Available IPD/Information:

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