Safety of Antithrombotic Heparin Proteoglycan Mimetic APAC in Peripheral Arterial Occlusive Disease and Chronic Limb-threatening Ischemia

NCT07352800 | Recruiting Phase 2 DMC

• 2 other identifiers: APLA-PAOD-CS022025-522390-11-00
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this study is to learn if a new medicine (called antiplatelet and anticoagulant \[APAC\]) can help the body to prevent blood clots and whether APAC is safe and well tolerated in patients with blocked or narrowed arteries in their legs (peripheral arterial occlusive disease \[PAOD\]), and in patients with severely restricted poor blood flow to the legs that threatens limb health (chronic limb-threatening ischemia \[CTLI\]). The study also aims to find the best dose of the medicine. The study consists of two parts: Part A will include patients with PAOD and CTLI, Part B will only include patients with CTLI who are having a procedure to restore blood flow in their legs. Both parts will be subdivided into two subgroups (A1 and A2, B1 and B2) which will test different APAC doses and compare single dosing to weekly dosing for 4 weeks. APAC is injected into the blood. The possible treatment response will be compared either to a placebo (a look-alike substance that contains no drug), or to the current standard treatment. Patients will participate in the study for up to 90 or 180 days. During this time, patients will be regularly examined and asked to answer questions concerning their quality of life.

Conditions

Peripheral Arterial Occlusive Disease; Chronic Limb-Threatening Ischemia

Outcome Measures

Primary Outcomes (2)

• Primary endpoint - Part A: Occurrence and severity of treatment-emergent adverse events (TEAEs)

  From baseline to Day 29 (Part A1) and Day 90 (Part A2) after the first dose of APAC

• Primary endpoint - Part B: Occurrence and severity of TEAEs

  From baseline to Day 90 after the first dose of APAC

Secondary Outcomes (31)

• Secondary endpoint 1 - Part A: Fontaine classification

  Assessed at screening (Day -28 to Day -1), at Day 29, Day 60 (Part A2 only) and Day 90 (Part A2) after the first dose of APAC

• Secondary endpoint 1 - Part A: Wound Ischemia foot Infection (WIfI) scoring

  Assessed at screening (Day -28 to Day -1), at Day 8, Day 15 (Part A2 only), Day 22 (Part A2 only), Day 29, Day 60 (Part A2 only) and Day 90 (Part A2) after the first dose of APAC

• Secondary endpoint 1 - Part A: Toe-brachial blood pressure index (TBI) and ankle-brachial systolic blood pressure index (ABI)

  Assessed at screening (Day -28 to Day -1) at Day 29, Day 60 (Part A2 only) and Day 90 (Part A2) after the first dose of APAC

• Secondary endpoint 1 - Part A2: Maximal walking distance in a treadmill exercise test

  Assessed at screening (Day -28 to Day -1), at Day 29, Day 60 and Day 90 after the first dose of APAC

• Secondary endpoint 2 - Part A: Changes in PD and PK, and other blood coagulation biomarkers - clotting time, clot formation time and activated clotting time

  Assessed at baseline (Day 1), Day 2, Day 8, Day 15 (only Part A2), Day 22 (only Part A2) and Day 29

Study Arms (9)

Part A1 (no endovascular procedure) - APAC

EXPERIMENTAL

Drug: APAC - dose level 0.50 mg/kg,

Part A1 (no endovascular procedure) - control

ACTIVE COMPARATOR

Other: Unfractionated heparin (UFH)

Part A2 (no endovascular procedure) - APAC dose level 1

EXPERIMENTAL

Drug: APAC dose level 1: 0.25 mg/kg,

Part A2 (no endovascular procedure) - APAC dose level 2

EXPERIMENTAL

Drug: APAC dose level 2: 0.50 mg/kg,

Part A2 (no endovascular procedure) - vehicle

OTHER

Other: Vehicle (sterile saline, NaCL 0.9%)

Part B1 (endovascular procedure) - APAC

EXPERIMENTAL

Drug: APAC (single periprocedural dose)

Part B1 (endovascular procedure) - control

ACTIVE COMPARATOR

Other: Unfractionated heparin (UFH)

Part B2 (endovascular procedure) - APAC

EXPERIMENTAL

Drug: APAC

Part B2 (endovascular procedure) - control

ACTIVE COMPARATOR

Other: Unfractionated heparin (UFH)

Interventions

APAC - dose level 0.50 mg/kg, DRUG

single i.v. dosing

Part A1 (no endovascular procedure) - APAC

Unfractionated heparin (UFH) OTHER

administered as standard of care

Part A1 (no endovascular procedure) - control; Part B1 (endovascular procedure) - control; Part B2 (endovascular procedure) - control

APAC dose level 1: 0.25 mg/kg, DRUG

weekly i.v. dosing for 4 consecutive weeks

Part A2 (no endovascular procedure) - APAC dose level 1

Vehicle (sterile saline, NaCL 0.9%) OTHER

weekly i.v. dosing for 4 consecutive weeks

Part A2 (no endovascular procedure) - vehicle

APAC dose level 2: 0.50 mg/kg, DRUG

weekly i.v. dosing for 4 consecutive weeks

Part A2 (no endovascular procedure) - APAC dose level 2

APAC (single periprocedural dose) DRUG

Dose is selected based on Part A data, periprocedural dosing.

Part B1 (endovascular procedure) - APAC

APAC DRUG

Dose is selected based on Part A and Part B, periprocedural dosing plus dosing for 4 consecutive weeks.

Part B2 (endovascular procedure) - APAC

Eligibility Criteria

• Age: Up to 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males aged 45-85 years and postmenopausal females (i.e., no menstrual periods for 12 months without an alternative medical cause) up to 85 years.
• Diagnosed with a. PAOD classification Fontaine stage III or IV , b. the total length of the treatment-targeted arterial segment ≥ 5 cm below the knee lesion(s) based on contrast-enhanced computed tomography angiography (CTA)/magnetic resonance angiography (MRA)/digital subtraction angiography (DSA) (Part B1 and B2), c. superficial forefoot wounds without overt infection and bone invasion (WIfI 0-1 and 2 limited to digits and WIfI infection 0-1) allowed, d. undergoing endovascular intervention. (In Part A1, if prescheduled endovascular intervention would take place before the Day 8 study visit, patient is not to be enrolled.)
• CTA/MRA/DSA with contrast agent performed within 3 months prior to study enrolment as part of diagnostics of PAOD, with results available in the patient's medical records.
• Patients should be treated with antithrombotic medication either acetylsalicylic acid (up to 100 mg once a day \[QD\]) or clopidogrel (up to 75 mg QD) for at least the preceding five days before the first APAC administration.
• Adequate lipid lowering therapy, as evaluated by the investigator.
• Capability and willingness to provide valid, voluntary written informed consent for the study.
• Males must be willing to use a condom and their female partners of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile \[hysterectomy, bilateral salpingectomy and bilateral oophorectomy\]) must be willing to use highly effective contraception while on study treatment. Highly effective methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; and sexual abstinence.
• Males must refrain from sperm donation while on study treatment.
• Males aged 45-85 years and postmenopausal females (i.e., no menstrual periods for 12 months without an alternative medical cause) up to 85 years.
• Diagnosed with a. PAOD classification Fontaine stage IIa and IIb, b. not prescheduled for endovascular revascularization within 90 days of first APAC administration.
• Moderate to severe arterial disease, ABI \< 0.7.
• Patients should be capable of performing evaluable treadmill exercise test.
• Patients should be treated with antithrombotic medication either acetylsalicylic acid (up to 100 mg QD) or clopidogrel (up to 75 mg QD) for at least the preceding five days before the first APAC administration.
• Adequate lipid lowering therapy, as evaluated by the investigator.
• Capability and willingness to provide valid, voluntary written informed consent for the study.

You may not qualify if:

• Any ischemic lesions of the heel and midfoot and lesions (wounds or gangrene) invading bones, joints, or tendons at metatarsophalangeal joints or more proximal sites.
• Acute limb-threatening ischemia (e.g., thromboembolic disease).
• Medical history of, or an existing aneurysm.
• Endovascular revascularization intervention is done from the contralateral side using cross-over access (Part B1 and B2).
• Medical history of, or condition known to be associated with impaired hemostasis, i.e., increased intracranial bleeding risk e.g., previous history of intracranial hemorrhage, subarachnoidal bleeding, hemorrhagic stroke, thrombotic or thromboembolic stroke, gastrointestinal bleeding within 6 months of enrolment, or retroperitoneal bleeding any time, or any inherited or acquired bleeding disorder, i.e., von Willebrand disease or hemophilia or other relevant diagnosis causing impaired hemostasis.
• Current use of therapeutic dose of anticoagulation (warfarin, apixaban, rivaroxaban, dabigatran, edoxaban, fondaparinux, or any heparin derivative) for any medical reason. (Use of dual pathway inhibition \[= acetylsalicylic acid 100 mg + rivaroxabahn 2.5 mg x 2\] is not a contraindication, but will be temporarily halted for the day of intervention and day of repeating dosing)
• Patients treated with combined antiplatelet agents: aspirin + P2Y12 antagonist (clopidogrel, ticagrelor, prasugrel).
• Diagnosis of autoimmune diabetes mellitus (Type 1 diabetes, or latent autoimmune diabetes in adults \[LADA\]) vasculitis, rheumatoid arthritis, inflammatory bowel diseases, or other general autoimmune diseases.
• Body mass index \> 35 kg/m\^2.
• Patients with clinically significant acute infection, as judged by the investigator.
• Use of non-steroidal anti-inflammatory medications within 2 weeks prior to the first dose of APAC or during the treatment period. If medication for pain is required, paracetamol or tramadol (e.g. an opioid patch) may be used.
• Use of selective serotonin reuptake inhibitor (SSRI) medication within 2 weeks prior to the first dose of APAC or during the treatment period.
• Peroral use of glycosaminoglycans or omega 3 or related products within 28 days before IMP treatment.
• Major surgery, major trauma or any endovascular intervention within the past 90 days or organ biopsy prior to the screening visit or scheduled for such an intervention during the study.
• Uncontrolled arterial hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg).

Sponsors & Collaborators

• Estimates OY: collaborator
• Aplagon Oy: lead
• LINK Medical Research AB: collaborator

Study Sites (3)

Helsinki University Hospital

Helsinki, 00290, Finland

RECRUITING

Tampere University Hospital

Tampere, Finland

RECRUITING

Turku University Hospital

Turku, Finland

RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Occlusive Disease 1; Chronic Limb-Threatening Ischemia

Interventions

Heparin; Sodium Chloride

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Jarna Hannukainen

  Aplagon Oy

  STUDY DIRECTOR

Central Study Contacts

Jarna Hannukainen

CONTACT

+358 400 633 061; jarna.hannukainen@aplagon.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Due to the severity of the disease and the planned treatment regimen, blinding is not applicable in order to ensure safety and proper clinical management of patients.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of two Parts - Part A and B, each divided into subparts 1 and 2. In Part A1, patients are randomized (2:1) to APAC and control groups. In Part A2, patients are randomized (2:2:1) to two APAC dose levels and control. In Part B (both subparts B1 and B2), patients will be randomized in 2:1 ratio to APAC and control groups.

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: January 20, 2026
• Study Start: January 29, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FI (3)