NCT07318610
Not yet recruiting
Phase 3
A Master Protocol for a Phase 3, Multicenter, Randomized Study to Evaluate the Efficacy and Safety of REGN7508 and REGN9933, Monoclonal Antibodies Against Factor XI, in Participants With Recent Lower Extremity Revascularization for Symptomatic Peripheral Artery Disease (ROXI-PALISADE)
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 7,050
- Primary Endpoint
- Time-to-first occurrence of a major thrombotic vascular event, consisting of Acute Limb Ischemia (ALI), major amputation (above the ankle) of vascular etiology, Myocardial Infarction (MI), ischemic stroke, or Cardiovascular (CV) death
Overview
Brief Summary
This study is researching 2 different experimental drugs called REGN7508 and REGN9933. The study is focused on people who have Peripheral Artery Disease (PAD), which means that the blood vessels in their arms and legs have become too narrow. People with PAD have a higher risk of getting blood clots after procedures like Lower Extremity Revascularization (LER), a procedure to improve blood flow in the legs and feet.
The aim of this study is to see how well REGN7508 and REGN9933 prevent life-threatening blood clots in participants with PAD who have recently had LER. The effects of REGN7508 and REGN9933, individually, will also be compared to rivaroxaban and a placebo.
The study is looking at several other research questions, including:
- What side effects might happen from taking the study drugs and how do they compare to the side effects of rivaroxaban
- How much study drug is in the blood at different times
- Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects)
- If the study drugs affect the ability of the blood to clot normally
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Cohort 1 of this study is double-blinded, and for Cohort 2 the participants, sponsor, and the investigators will be blinded to REGN7508 or REGN9933, but rivaroxaban will be administered as open-label.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Successful LER distal to the external iliac artery for ischemia due to atherosclerotic disease within 10 days prior to randomization as described in the protocol
- •At least 1 enrichment factor for major thrombotic vascular events:
- •Bypass with prosthetic graft
- •Endovascular treatment with stenting
- •Target lesion length \>15 cm
- •History of LER or amputation for PAD prior to qualifying LER
- •Type 2 diabetes mellitus requiring treatment
- •Comorbid symptomatic coronary artery disease as described in the protocol
- •Chronic kidney disease as described in the protocol
- •Age ≥75 years
Exclusion Criteria
- •Has any active clinical condition requiring therapeutic anticoagulation after the index revascularization including known triple positive antiphospholipid syndrome
- •Has known bleeding diathesis, platelet count \<50,000/mm\^3 or history of non-traumatic intracerebral hemorrhage, known cerebral amyloid angiopathy, or known unrepaired cerebrovascular malformations
- •Has recent coronary revascularization as described in the protocol
- •For Cohort 2 only: Has Glomerular Filtration Rate (GFR) \<15 mL/min/1.73m\^2 within 14 days prior to randomization or on dialysis or expected to be started on dialysis within the next 12 weeks starting from randomization
- •Has any other condition or therapy which would make the participant unsuitable for this study or not allow participation for the full planned study period
- •Has allergy, hypersensitivity, or other contraindication to REGN7508, REGN9933, or rivaroxaban (Cohort 2 only) or their excipients
- •Note: Other Protocol Defined Inclusion/ Exclusion Criteria Apply
Arms & Interventions
Cohort 2
Experimental
Intervention: Rivaroxaban (Drug)
Cohort 1
Experimental
Intervention: REGN7508 (Drug)
Cohort 1
Experimental
Intervention: REGN9933 (Drug)
Cohort 1
Experimental
Intervention: Placebo (Drug)
Cohort 2
Experimental
Intervention: REGN7508 (Drug)
Cohort 2
Experimental
Intervention: REGN9933 (Drug)
Outcomes
Primary Outcomes
Time-to-first occurrence of a major thrombotic vascular event, consisting of Acute Limb Ischemia (ALI), major amputation (above the ankle) of vascular etiology, Myocardial Infarction (MI), ischemic stroke, or Cardiovascular (CV) death
Time Frame: Approximately up to 42 months
Cohort 1
Time-to-first occurrence of International Society of Thrombosis and Hemostasis (ISTH) major or Clinically Relevant Non-major (CRNM) bleeding
Time Frame: Approximately up to 42 months
Cohort 1 and 2
Secondary Outcomes
- Time-to-first occurrence of Major Adverse Limb Event (MALE)(Approximately up to 42 months)
- Time-to-first occurrence of ALI, major amputation (above the ankle) of vascular etiology, MI, ischemic stroke or coronary death(Approximately up to 42 months)
- Time-to-first occurrence of vascular hospitalization for a coronary or peripheral event of thrombotic nature(Approximately up to 42 months)
- Time-to-all-cause mortality(Approximately up to 42 months)
- Total (first and subsequent) occurrences of major thrombotic vascular events, consisting of ALI, major amputation (above the ankle) of vascular etiology, MI, ischemic stroke, or CV death(Approximately up to 42 months)
- Time-to-first occurrence of an expanded thrombotic vascular event, consisting of ALI, major amputation (above the ankle) of vascular etiology, MI, ischemic stroke, CV death, unplanned index limb revascularization, or Venous Thromboembolism (VTE)(Approximately up to 42 months)
- Time-to-first occurrence of ALI, major amputation of vascular etiology, MI, ischemic stroke, or all-cause mortality(Approximately up to 42 months)
- Time-to-first occurrence of unplanned index limb revascularization for ischemia(Approximately up to 42 months)
- Occurrence of Treatment-Emergent Adverse Event (TEAEs)(Approximately up to 45 months)
- Total (first and subsequent) occurrences of ALI, major amputation (above the ankle) of vascular etiology, MI, all-cause stroke, or CV death(Approximately up to 42 months)
- Total (first and subsequent) occurrences of ALI, major amputation (above the ankle) of vascular etiology, MI, all-cause stroke, CV death, unplanned index limb revascularization, or VTE(Approximately up to 42 months)
- Time-to-first occurrence of VTE(Approximately up to 42 months)
- Occurrence of ADA to REGN9933 over time(Approximately up to 45 months)
- Concentrations of REGN7508 over time(Approximately up to 45 months)
- Concentrations of REGN9933 over time(Approximately up to 45 months)
- Change from baseline in Prothrombin Time (PT)/International Normalization Ratio (INR) over time(Approximately up to week 9)
- Time-to-first occurrence of Major Adverse Cardiovascular Event (MACE)(Approximately up to 42 months)
- Time-to-first occurrence of a major thrombotic vascular event or ISTH fatal/critical organ bleeding (net clinical benefit)(Approximately up to 42 months)
- Severity of TEAEs(Approximately up to 45 months)
- Magnitude of ADA to REGN9933 over time(Approximately up to 45 months)
- Change from baseline in activated Partial Thromboplastin Time (aPTT) over time(Approximately up to week 9)
- Time-to-first occurrence of Thrombolysis in Myocardial Infarction (TIMI) major bleeding(Approximately up to 42 months)
- Occurrence of Anti-Drug Antibody (ADA) to REGN7508 over time(Approximately up to 45 months)
- Time-to-first occurrence of a major thrombotic vascular event(Approximately up to 42 months)
- Magnitude of ADA to REGN7508 over time(Approximately up to 45 months)
- Total (first and subsequent) occurrences of expanded thrombotic vascular events(Approximately up to 42 months)
Investigators
Similar Trials
Recruiting
Phase 2
A Trial to Learn How Well REGN9933 and REGN7508 Work for Preventing Blood Clots, and How Safe They Are, in Adults Who Have a Peripherally Inserted Central Catheter (PICC)2023-508603-21-00Regeneron Pharmaceuticals Inc.93
Recruiting
Phase 3
Study of Bet v1 Antibodies Effect on Eye Allergy Symptoms in Adolescents and Adults With Birch Pollen AllergyNCT07309432Regeneron Pharmaceuticals350
Recruiting
Phase 1/2
CO43923 Master Protocol: A Study Evaluating the Safety and Efficacy of Multiple Treatments in Patients with Multiple Myeloma CO43923 Substudy 1: A Study to Collect Patient-Level Data in Patients with Multiple Myeloma CO43923 Substudy 2 Cevos + Len Treatment: A Study Evaluating the Safety and Efficacy of Cevostamab in Combination with Lenalidomide in Patients with Cytogenetic High-Risk Features Receiving Maintenance Treatment After First Response from Multiple Myeloma Post-Stem Cell Transplant CO43923 Substudy 4 Cevostamab+ Iberdomide Treatment: A Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cevostamab in Combination with Iberdomide in Patients with Relapsed or Refractory Multiple Myeloma2023-504484-16-00F. Hoffmann-La Roche AG32
Not yet recruiting
Phase 1/2
A trial to learn how safe saruparib is and how well it works in people with advanced ovarian cancer2024-519044-32-00AstraZeneca AB16
Not yet recruiting
Not Applicable
Study of QLC5513 in Combination With Epalolimab Tovolimab (QL1706) ± Platinum in Patients With Advanced or Metastatic Malignant Solid TumorsNCT07272590Qilu Pharmaceutical Co., Ltd.290