Inclusion Criteria (Parts A1, B1 and B2):
1. 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.
2. 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.)
3. 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.
4. 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.
5. Adequate lipid lowering therapy, as evaluated by the investigator.
6. Capability and willingness to provide valid, voluntary written informed consent for the study.
7. 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.
8. Males must refrain from sperm donation while on study treatment.
Inclusion Criteria (Part A2):
1. 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.
2. Diagnosed with a. PAOD classification Fontaine stage IIa and IIb, b. not prescheduled for endovascular revascularization within 90 days of first APAC administration.
3. Moderate to severe arterial disease, ABI \< 0.7.
4. Patients should be capable of performing evaluable treadmill exercise test.
5. 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.
6. Adequate lipid lowering therapy, as evaluated by the investigator.
7. Capability and willingness to provide valid, voluntary written informed consent for the study.
8. 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); IUD; IUS; bilateral tubal occlusion; vasectomized partner; and sexual abstinence.
9. Males must refrain from sperm donation while on study treatment.
Exclusion Criteria:
1. 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.
2. Acute limb-threatening ischemia (e.g., thromboembolic disease).
3. Medical history of, or an existing aneurysm.
4. Endovascular revascularization intervention is done from the contralateral side using cross-over access (Part B1 and B2).
5. 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.
6. 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)
7. Patients treated with combined antiplatelet agents: aspirin + P2Y12 antagonist (clopidogrel, ticagrelor, prasugrel).
8. 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.
9. Body mass index \> 35 kg/m\^2.
10. Patients with clinically significant acute infection, as judged by the investigator.
11. 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.
12. Use of selective serotonin reuptake inhibitor (SSRI) medication within 2 weeks prior to the first dose of APAC or during the treatment period.
13. Peroral use of glycosaminoglycans or omega 3 or related products within 28 days before IMP treatment.
14. 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.
15. Uncontrolled arterial hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg).
16. Blood hemoglobin concentration \<120 g/L or \> 170 g/L (men) and \<110 g/L or \>160 g/L (women) at screening.
17. Blood platelet count \<150 x 10\^9/L or \> 450 x10\^9/L and/or leukocyte count in the lower reference range or not above \>12 x 10\^9/L.
18. Clinically significantly prolonged plasma PT (\> 1.2-fold) or a value of less than 50% (when normal reference range is 70-130%).
19. APTT above the upper limit of the reference range.
20. Patients with a medical history of heparin-induced thrombocytopenia.
21. Patients with known significant liver disease, incl. an alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) level \> 2.5 x the upper limit of normal (ULN) at screening.
22. A diagnosis of severe chronic kidney disease, defined as having an eGFR category 4 or 5 (eGFR \< 30 mL/min/1.73 m2 as per calculation of Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\]) or albuminuria stage A3 (uACR \>300 mg/g).
23. Patients with an active malignancy, or who have received treatment for any malignancy including bone marrow transplantation within 5 years before the screening visit, except for localized basal cell or squamous cell skin cancer that has been cured at least 90 days before screening.
24. Previous treatment with APAC.
25. Patients with known allergy or hypersensitivity to heparin, or heparin products, APAC, and/or antiplatelet agents (e.g., aspirin or clopidogrel), and protamine sulphate, the reversal agent for APAC.
26. Participation in an investigational drug or device study within 90 days prior to screening.
27. Patients who have ever received treatment with a gene therapy.
28. Patients with known antiphospholipid antibody syndrome or other known significant thrombophilia (homozygosity for FV Leiden or FIIG20210A mutation, or phospholipid antibody syndrome, deficiency of antithrombin, protein C or protein S or combined thrombophilia).
29. Any concomitant disease or condition or treatment that could interfere with, or the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the patient in this study as judged by the investigator.
30. Patients with severe comorbidities and limited life expectancy as judged by the investigator.
31. Patients unable or unwilling to comply with the protocol or to cooperate fully with the investigator or site personnel.
32. Patients with current and/or history of drug abuse (defined as illicit drug use) or alcohol abuse (defined as daily consumption of more than 23-24 and 12-16 alcoholic drinks per week in males and females, respectively).
