Vortosiran for VTE Prevention

NCT07850453 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: RC03T0032026-525479-15
• Study Type: interventional
• Target: 150
• Locations: 4 countries
• Sites: 30

Brief Summary

Blood clots remain a serious cause of illness and death. Long-term treatment and prevention of these clots with blood thinners is often limited by bleeding risk, drug interactions, and daily dosing, leading many patients to stop treatment early. Both cancer and chemotherapy further increase the risk of clot formation. Vortosiran is an injectable therapy that lowers Factor XI (one of the body's natural clotting helpers) production in the liver, leading to a strong and long-lasting reduction in blood clotting activity with less risk of bleeding compared to current available treatments. Studies conducted so far have shown that vortosiran is safe and shows a dose-dependent Factor XI suppression (that is, a higher dose results in a higher level of suppression) that lasts for several months, supporting testing using a limited number of injections in patients who are at higher risk of blod clot formation. This study aims to study how safe and effective vortosiran is in patients who have had blood clots in the past and in cancer patients who are at high risk of developing blood clots.

Conditions

Venous Thromboembolism (VTE); Cancer; Pulmonary Embolism (Diagnosis)

Keywords

VTE; Venous Thromboembolism; siRNA; Phase 2; RCT

Outcome Measures

Primary Outcomes (2)

• Primary objective

  To evaluate the effect of two dose levels of vortosiran on coagulation Factor XI (FXI) activity.

  At Week 8

• Primary endpoint

  Percentage change from baseline in FXI activity, compared with placebo.

  Baseline to Week 8.

Secondary Outcomes (5)

• Secondary objective

  Up to week 56

• Secondary objective

  0 [pre-dose] to 24 hours after dosing.

• Secondary objective

  At week 16

• Secondary Objective

  At week 16

• Secondary objective

  At week 16

Study Arms (3)

Low-dose group

ACTIVE COMPARATOR

Drug: Vortosiran

High-dose group

ACTIVE COMPARATOR

Drug: Vortosiran

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Vortosiran DRUG

Vortosiran, active drug.

High-dose group; Low-dose group

Placebo DRUG

Placebo that is identical in appearance of active IMP.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort A
• Adult male and female participants (≥18 years) meeting the specified below criteria for Cohort A.
• Postmenopausal women are eligible without additional contraceptive measures.
• Postmenopausal status is defined as:
• Age ≥55 years with ≥12 months of spontaneous amenorrhoea, or
• Age \<55 years with ≥12 months of spontaneous amenorrhoea and follicle-stimulating hormone in the postmenopausal range, or surgical menopause (bilateral oophorectomy, with or without hysterectomy) documented in the medical history.
• Women of childbearing potential must agree to use highly effective contraception for the duration of trial treatment and for the specified post-treatment period.
• Able and willing to provide written informed consent and to comply with trial procedures and follow-up.
• Objectively confirmed symptomatic index of the lower limbs at the popliteal vein or more proximal, and/or symptomatic PE, documented by objective imaging modalities (eg. DVT: compression ultrasonography/duplex ultrasound; computed tomography/magnetic resonance venography; or contrast venography. PE: computed tomography pulmonary angiography; high probability ventilation/perfusion scan; or pulmonary angiography).
• Completed 3 to 12 months of standard therapeutic anticoagulant therapy for the index VTE episode (vitamin K antagonists, DOACs, low molecular weight heparin, or fondaparinux at therapeutic dose) at least 2 weeks before randomization.
• Cohort B
• Adult male and female participants (≥18 years) meeting the specified below criteria for Cohort B.
• Postmenopausal women are eligible without additional contraceptive measures.
• Postmenopausal status is defined as:
• Age ≥55 years with ≥12 months of spontaneous amenorrhoea, or

You may not qualify if:

• Cohort A
• Women who are pregnant, currently breastfeeding, or planning pregnancy during the trial or within the defined post-treatment period are not eligible.
• Evidence of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection at Screening, defined as any of the following:
• Positive hepatitis B surface antigen (HBsAg), or positive total hepatitis B core antibody (anti-HBc) with detectable HBV DNA;
• Positive hepatitis C virus antibody (anti-HCV) with detectable HCV RNA; or
• Reactive HIV-1/2 antigen/antibody test confirmed by a positive confirmatory test.
• Participants who are total anti-HBc-positive must undergo HBV DNA testing, and participants who are anti-HCV-positive must undergo HCV RNA testing. Participants with undetectable HBV DNA or HCV RNA may be eligible provided there is no clinical or laboratory evidence of active liver disease.
• Planned surgery that may change VTE/bleeding risk during the trial period and no recent surgery (≤2 weeks prior screening).
• Any serious medical, psychiatric, or social condition that, in the investigator's opinion, would interfere with trial participation, compliance, or interpretation of trial results.
• eGFR \<30 mL/min (calculated per CKD-EPI 2021, expected to be reported in mL/min per 1.73 m2)
• Clear indication for indefinite/extended anticoagulation for any reason, including but not limited to:
• Atrial fibrillation or flutter requiring anticoagulation.
• Mechanical heart valve or moderate/severe rheumatic mitral stenosis.
• Recent or ongoing VTE requiring therapeutic anticoagulation (symptomatic or incidental).
• Known antiphospholipid syndrome with a high-risk profile, defined as the presence of lupus anticoagulant.

Sponsors & Collaborators

• Fortrea: collaborator
• Ribocure Pharmaceuticals AB: lead

Study Sites (30)

Multiprofile Hospital For Active Treatment - Pazardzhik AD

Pazardzhik, Bulgaria

Location

Specialized Hospital for Active Treatment in Cardiology - Medica Cor EAD

Rousse, Bulgaria

Location

Acibadem City Clinic Tokuda University Hospital EAD

Sofia, Bulgaria

Location

Multiprofile Hospital for Active Treatment "National Cardiology Hospital" EAD

Sofia, Bulgaria

Location

Multiprofile Hospital for Active Treatment "National Cardiology Hospital" EAD

Sofia, Bulgaria

Location

University Hospital for Active Treatment and Emergency Medicine N.I. Pirogov EAD

Sofia, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Alexandrovska"

Sofia, Bulgaria

Location

Multiprofile District Hospital for Active Treatment "Dr. Stefan Cherkezov" AD

Veliko Tarnovo, Bulgaria

Location

Centre Oncologie Radiotherapie (CORT 37)

Chambray-lès-Tours, France

Location

Louis-Mourier (AP-HP)

Colombes, France

Location

CHU de Grenoble

Grenoble, France

Location

Hôpital Européen Georges Pompidou (HEGP)

Paris, France

Location

Cardiology Office Individual Specialist Medical Practice Elżbieta Dułak

Gdynia, Poland

Location

Oddział Kardiologii SPS Szpital Zachodni im św Jana Pawła iI

Grodzisk Mazowiecki, Poland

Location

Uniwersytet Jagiellonski Collegium Medicum

Krakow, Poland

Location

"Department of Cardiology European Health Center Otwock"

Otwock, Poland

Location

University Clinical Research Support Center of Medical University in Poznan

Poznan, Poland

Location

Clinical Oncology Department, Mazowiecki Szpital Wojewódzki

Siedlce, Poland

Location

Aidport Sp. z o.o.

Skorzewo, Poland

Location

Zachodniopomorskie Centrum Onkologii

Szczecin, Poland

Location

Centrum Medyczne LUX MED sp zoo ul 1 Sierpnia 8, 02-143 Warszawa

Warsaw, Poland

Location

Klinika Sienna Sp. z o.o.

Warsaw, Poland

Location

Maria Skłodowska-Curie National Research Institute of Oncology

Warsaw, Poland

Location

Gral Medical - Oncofort Pitesti

Piteşti, Romania

Location

Satu Mare County Emergency Hospital

Satu Mare, Romania

Location

Spitalul European Polisano - Constitutiei Sibiu

Sibiu, Romania

Location

Sigmedical Services S.R.L.

Suceava, Romania

Location

Centrul Medical Cardiomed

Târgu Mureş, Romania

Location

Spitalul Clinic Judeţean Mureş

Târgu Mureş, Romania

Location

Institutului de Boli Cardiovasculare Timişoara

Timișoara, Romania

Location

Related Publications (11)

• Salomon O, Steinberg DM, Dardik R, Rosenberg N, Zivelin A, Tamarin I, Ravid B, Berliner S, Seligsohn U. Inherited factor XI deficiency confers no protection against acute myocardial infarction. J Thromb Haemost. 2003 Apr;1(4):658-61. doi: 10.1046/j.1538-7836.2003.00195.x.

  PMID: 12871398 BACKGROUND

• Doggen CJ, Rosendaal FR, Meijers JC. Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: Opposite and synergistic effects of factors XI and XII. Blood. 2006 Dec 15;108(13):4045-51. doi: 10.1182/blood-2005-12-023697. Epub 2006 Aug 24.

  PMID: 16931632 BACKGROUND

• Konings J, Govers-Riemslag JW, Spronk HM, Waltenberger JL, ten Cate H. Activation of the contact system in patients with a first acute myocardial infarction. Thromb Res. 2013 Jul;132(1):138-42. doi: 10.1016/j.thromres.2013.05.016. Epub 2013 Jun 7.

  PMID: 23746628 BACKGROUND

• Paszek E, Pociask E, Zabczyk M, Piorkowski A, Butenas S, Legutko J, Undas A. Active factor XI is associated with the risk of cardiovascular events in stable coronary artery disease patients. Atherosclerosis. 2022 Apr;346:124-132. doi: 10.1016/j.atherosclerosis.2022.02.009. Epub 2022 Feb 11.

  PMID: 35246318 BACKGROUND

• Lewandowska MD, Connors JM. Factor XI Deficiency. Hematol Oncol Clin North Am. 2021 Dec;35(6):1157-1169. doi: 10.1016/j.hoc.2021.07.012. Epub 2021 Sep 15.

  PMID: 34535287 BACKGROUND

• Key NS. Epidemiologic and clinical data linking factors XI and XII to thrombosis. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):66-70. doi: 10.1182/asheducation-2014.1.66. Epub 2014 Nov 18.

  PMID: 25696836 BACKGROUND

• Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008 May 15;111(10):4902-7. doi: 10.1182/blood-2007-10-116327. Epub 2008 Jan 23.

  PMID: 18216292 BACKGROUND

• Khan F, Rahman A, Carrier M, Kearon C, Weitz JI, Schulman S, Couturaud F, Eichinger S, Kyrle PA, Becattini C, Agnelli G, Brighton TA, Lensing AWA, Prins MH, Sabri E, Hutton B, Pinede L, Cushman M, Palareti G, Wells GA, Prandoni P, Buller HR, Rodger MA; MARVELOUS Collaborators. Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis. BMJ. 2019 Jul 24;366:l4363. doi: 10.1136/bmj.l4363.

  PMID: 31340984 BACKGROUND

• Walsh M, Bethune C, Smyth A, Tyrwhitt J, Jung SW, Yu RZ, Wang Y, Geary RS, Weitz J, Bhanot S; CS4 Investigators. Phase 2 Study of the Factor XI Antisense Inhibitor IONIS-FXIRx in Patients With ESRD. Kidney Int Rep. 2021 Nov 24;7(2):200-209. doi: 10.1016/j.ekir.2021.11.011. eCollection 2022 Feb.

  PMID: 35155859 BACKGROUND

• Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A, Kuruvilla P, Hill D, Spadafora S, Marquis K, Trinkaus M, Tomiak A, Lee AYY, Gross PL, Lazo-Langner A, El-Maraghi R, Goss G, Le Gal G, Stewart D, Ramsay T, Rodger M, Witham D, Wells PS; AVERT Investigators. Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. N Engl J Med. 2019 Feb 21;380(8):711-719. doi: 10.1056/NEJMoa1814468. Epub 2018 Dec 4.

  PMID: 30511879 BACKGROUND

• Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007 Mar;5(3):632-4. doi: 10.1111/j.1538-7836.2007.02374.x. No abstract available.

  PMID: 17319909 BACKGROUND

MeSH Terms

Conditions

Venous Thromboembolism; Neoplasms; Pulmonary Embolism; Disease

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Anders Gabrielsen, MD, PhD

  Ribocure Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Rebeckha Magnusson, Head Clinical Operations

CONTACT

+46 31 72 07 800; rebeckha.magnusson@ribocure.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase II trial will be conducted in two cohorts. Cohort A and Cohort B are independently enrolled and randomized. Participants are randomized (2:2:1) to low-dose vortosiran, high-dose vortosiran, or matched placebo, with dosing on Day X and Day Y and follow-up through Week 56. This trial aims to evaluate vortosiran in two complementary populations where FXI suppression could provide clinically relevant benefit and where the risk-benefit of conventional anticoagulation is often challenging.

Study Record Dates

• First Submitted: September 17, 2026
• First Posted: September 30, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: September 30, 2026

Record last verified: 2026-09

Locations

FR (4); RO (7); PL (11); BU (8)