Evaluation of Safety, Tolerability and Preliminary Efficacy of Etrinabdione in Patients With Peripheral Arterial Disease (CLAUDIA)

A Phase IIa Open Label, Dose-Finding, Clinical Trial to Evaluate Safety, Tolerability and Preliminary Efficacy of Etrinabdione in Patients With Peripheral Arterial Disease (PAD)

The goal of this clinical trial is to study the safety and tolerability of Etrinabdione in adult patients with peripheral arterial disease. It will also learn about the preliminary efficacy of Etrinabdione. The main questions it aims to answer are:

Has Etrinabdione an acceptable safety/tolerability profile during 12 months?

Do the patients show any improvement in any of the tests included in the protocol for this disease?

Researchers will test first the low dose of Etrinadione. If the product is safe at 3 months, the high dose can start.

Participants will:

Take Etrinabdione twice a day for 12 months. Visit the clinic once every 4 weeks for checkups and tests.

Study Overview

• Status: Not yet recruiting
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Drug: Etribnabdione 25 mg BID; Drug: Etribnabdione 50 mg BID

Detailed Description

This is a single center, open-label Phase IIa clinical study. The study will be conducted with 2 treatment arms 25 mg BID and 50 mg BID.

The study consists of a Screening Period, a Treatment Period, and a Follow-up Period. Total duration 14 months.

Subjects who meet the inclusion criteria and do not meet the exclusion criteria at screening will start with the lower dose (25 mg BID). When the 12 patients have been treated for 3 months and the PK and safety data are evaluated by the regulatory authority, the Sponsor and the site investigators, the high dose (50 mg BID) will be released.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Córdoba, Spain, 14014
    • Hospital Universitario Reina Sofía

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing and able to provide informed consent and capable of understanding and complying with the protocol;
• Subjects classified as critical limb ischemia (CLI) Rutherford Category 2 or 3 (moderate or severe) claudication;
• Diabetes mellitus type 2 with HbA1c < 9%;
• In case of treatment for PAD, the subject is controlled on medical therapy indicated for CLI;
• A female patient is eligible to participate if she is not pregnant, not breastfeeding, and agrees to use a highly effective method of contraception;
• A male patient with a female partner of childbearing potential is eligible if he agrees to use acceptable method of contraception.

Exclusion Criteria:

• Planned surgical or endovascular revascularization on the index leg within the next 12 months;
• Failed surgical or endovascular revascularization on the index leg within 10 days prior to screening;
• Amputation at or above the talus on the index leg;
• Planned major amputation within the first month after screening;
• On the index leg, use of concomitant wound treatments not currently approved for ischemic wound-healing within 30 days prior to screening or plans to initiate new treatments to the index leg during the trial;
• Uncontrolled or untreated proliferative retinopathy;
• Blood clotting disorder not caused by medication;
• Severe hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure;
• Evidence of moderate to severe hepatocellular dysfunction;
• Positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus (HBV), hepatitis C virus (HCV) or Treponema Pallidum;
• Subjects who may not be healthy enough to successfully complete all protocol requirements, or who are not expected to survive more than 12 months, or in whom results may be particularly difficult to assess.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose; 25 mg BID	Drug: Etribnabdione 25 mg BID; The trial will start with the lower dose. When the 12 patients have been treated for 3 months and the PK and safety data are evaluated by the regulatory authority, the Sponsor and the site investigators, the high dose (50 mg BID) will be released.
Experimental: High dose; 50 mg BID	Drug: Etribnabdione 50 mg BID; The treatment will start when the regulatory authority, the sponsor and the site investigators have reviewed the low dose safety and pharmacokinetics data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Treatment Emergent Adverse Events (TEAEs)	This safety outcome combines the measure of the number of subjects experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatments.	13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascularization	The angiogenesis induced by Etrinabdione treatment will be assessed by the evaluation of the peripheral arterial system of affected limbs by computed tomography angiography.	Baseline, 6 and 12 months
Absolute claudication time	The claudication time will be quantitatively measured by standardized treadmill test using a graded exercise protocol.	Baseline, 3, 6 and 12 months
Hemodynamic	The Ankle/Brachial Index (ABI) is a diagnostic measure used to assess blood flow and detect potential vascular abnormalities. It will be calculated as the ratio of systolic blood pressure at the ankle level (posterior tibial artery or pedia) divided by the systolic blood pressure obtained on the arm (humeral artery).	Baseline, 3, 6 and 12 months
Stenosis	Doppler ultrasound will be performed in the affected lower limbs at the level of the common femoral artery, superficial femoral artery, popliteal artery, posterior tibial artery and pedia artery.	Baseline, 3, 6 and 12 months
Disease specific quality of life questionnaire (VascuQoL-6)	The questionnaire includes 6 questions with 4 possible answers, scoring from 1 to 4. The lower the score, the worse the patient's perceived quality of life.	Baseline, 3, 6 and 12 months
Tissue oxigenation	Measure the local oxygen released from the capillaries through the skin by transcutaneous oximetry.	Baseline, 3, 6 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profile of Etrinabdione in terms of maximum observed plasma concentration (Cmax).	The point of maximum concentration of Etrinabdione in plasma.	pre-dose and 3 hours post dose) at Day 1 and months 1, 3, 6, 12, and 13 months.
Pharmacokinetic profile of Etrinabdione in terms of time to peak drug concentration (Tmax).	The time of Etrinabdine to reach its maximum concentration in the body after administration	pre-dose and 3 hours post dose) at Day 1 and months 1, 3, 6, 12, and 13 months.
Pharmacokinetic profile of Etrinabdione in terms of area under the plasma concentration-time curve (AUC).	Total systemic exposure to Etrinabdione.	pre-dose and 3 hours post dose) at Day 1 and months 1, 3, 6, 12, and 13 months.
Determination of potential accumulation of Etrinabdione.	Etrinabdione plasma through level.	pre-dose and 3 hours post dose) at Day 1 and months 1, 3, 6, 12, and 13 months.
Change in blood levels of disease/mechanism of action biomarkers measured by proximity extension assay and next-generation sequencing. All levels of plasma proteins will be provided in normalized protein expression units (NPX).	von Willebrand factor, Angiogenin, EPO, HGF, VEGF, FGF-2, PDGF, Endoglin, Endothelin-1, IL-1, TNFa, IL-6, IL-17, ICAM-1, IL-18, Proteinase-activated receptor 1, Angiopoietin-1, Endothelial cell-specific molecule 1, IL-18 and MCP1	Day 1 and months 1, 3, 6, 12, and 13 months.

Collaborators and Investigators

• Sponsor: VivaCell Biotechnology España

Publications and helpful links

General Publications

• Garcia-Martin A, Prados ME, Lastres-Cubillo I, Ponce-Diaz FJ, Cerero L, Garrido-Rodriguez M, Navarrete C, Pineda R, Rodriguez AB, Munoz I, Moya J, Medeot A, Moreno JA, Chacon A, Garcia-Revillo J, Munoz E. Etrinabdione (VCE-004.8), a B55alpha activator, promotes angiogenesis and arteriogenesis in critical limb ischemia. J Transl Med. 2024 Nov 6;22(1):1003. doi: 10.1186/s12967-024-05748-w.

Helpful Links

• Company website

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: January 12, 2025
• First Posted (Actual): January 14, 2025

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Claudication; Peripheral Vascular Disease; Vascular Disease; Peripheral Artery Disease; Critical Limb Ischemia; Arterial Occlusive Disease; Chronic Limb Threatening Ischemia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Atherosclerosis; Arteriosclerosis; Ischemia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Limb-Threatening Ischemia; Vascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication; Arterial Occlusive Diseases; BID protein, human
• Other Study ID Numbers: Etrinabdione-PAD02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No