Phase 1/2, Open label & double-blind randomized placebo-controlled study to assess the feasibility of BGC101 (EnEPC) in the treatment of peripheral arterial disease (PAD) with critical limb ischemia (CLI)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biogencell Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

23 Jan 2024 → ongoing

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BioGenCell Ltd

External identifiers

EU CT number

2024-516665-36-00

EudraCT number

2017-000993-12

ClinicalTrials.gov

NCT02805023

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate the feasibility, safety and efficacy of BGC101 in the treatment of patients suffering from PAD with CLI, who have not responded to the standard of care (SOC) including prior limb revascularization and do not have the option of further revascularization treatment.

Secondary objectives 1

1. To further assess the safety and efficacy of BGC101 versus placebo on clinical symptoms, clinical signs, and rate of amputation.

Conditions and MedDRA coding

Peripherial arterial disease (PAD) & Chronic-Limb Threatening Ischemia (CLTI) patients who have not responded to standard pharmacological treatment or control of risk factors, and/or had a revascularisation with continued presence of smaller vessel (microvasculature) disease, and do not have the option of a revascularization treatment.

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female patient able to complete the study and comply with instructions
2. Capable of understanding the purpose of the study and the contents of the informed consent form
3. Aged at least 18 years
4. Non-pregnant and non-lactating female patients
5. Have the clinical indications diagnostic of CLI based on Rutherford category 4-5
6. Have at least one of the hemodynamic indicators of severe peripheral arterial occlusive disease (WIfI ischemia grade ≥2): • Toe pressure <40 mmHg • Ankle pressure <70 mmHg • TcPO2 < 40mmHg
7. Meeting one of the following conditions: a. Poor candidate for standard revascularization treatment for peripheral arterial disease due to unfavorable anatomy or high surgical/intervention risk based on the patient’s underlying comorbidities. b. After undergoing clinically ineffective revascularization. c. Four weeks or more after a revascularization failure

Exclusion criteria 29

1. Severe, uncorrected aorto-iliac and/or common femoral artery disease, i.e. absent femoral pulse or monophasic common femoral artery Doppler waveform
2. Concurrent therapy that, in the Investigator’s opinion, would interfere with the evaluation of the feasibility of the study medication
3. Treatment with any investigational product within the last 6 months or enrollment in any active study involving the use of investigational devices or drugs
4. Presence of any other condition or circumstance that, in the judgment of the investigator, might negatively impact the outcomes of the treatment under investigation
5. Prognosis of a major amputation (below or above the knee), within 4 weeks after screening
6. Severe wound (WIfI wound grade 2 or 3)
7. Significant ongoing infection (WIfI infection grade 2 or 3)
8. Relative or absolute contraindications for intramuscular injections at the intended treatment site, in cases such as severe skin lesions, severe edema or morbid obesity, based on clinician opinion
9. Patient suffering from active vasculitis
10. Blood transfusions during the preceding 4 weeks (to exclude the potential of non-autologous cells in the harvested blood)
11. Hemoglobin (Hb) less than 9 g/dL
12. Patient with HbA1C > 8.5%
13. Myocardial infarction, cerebral infarction, uncontrolled myocardial ischemia or persistent severe heart failure (ejection fraction [EF] < 25%) during the preceding 3 months
14. Heart failure (New York Heart Association [NYHA] 3-4)
15. Significant valvular disease or less than 4 weeks after valve replacement or repair
16. Renal failure (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m², chronic kidney damage stage 4-5)
17. Liver failure, Model for End-stage Liver Disease (MELD) scores 15 and higher
18. Liver function tests more than three times normal upper limit (normal limits being defined in each local laboratory) (glutamic-oxaloacetic transaminase [GOT], glutamic-pyruvic transaminase [GPT], alkaline phosphatase [AlkP], gammaglutamyl transferase [GGT], lactate dehydrogenase [LDH])
19. Abnormal coagulation tests when not under warfarin (normalized prothrombin time [PT INR] >2)
20. Pregnant or lactating women at entry of study
21. People who are unwilling to agree to use acceptable methods of contraception during the study
22. Malignancy within the preceding 3 years, except basal cell carcinoma
23. Concurrent acute infectious disease with septicemia
24. Chronic infectious disease (human immunodeficiency virus-1 [HIV-1], human immunodeficiency virus-2 [HIV-2], hepatitis B virus [HBV], hepatitis C virus [HCV])
25. Immunodeficiency syndrome
26. Raynaud’s syndrome
27. Systemic treatment with cytotoxic and/or immunosuppressive treatment
28. Inability to communicate (that may interfere with the clinical evaluation of the patient)
29. Patient unlikely to be available for follow-up

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary safety endpoints will consist of: • Incidence and proportion of incidence between treatment arms of adverse events of specific interest (AESI) and injection-related AE • Incidence of serious adverse events (SAEs) including SAEs related or probably related to the treatment • Vital signs and physical examination • Safety laboratory values of hematology, blood chemistry, and urinalysis • Local tolerability (injection site reaction)
2. The primary efficacy endpoints will consist of: • Major amputation (below or above the knee) rate at Month 12 • Major amputation-free survival (AFS) rate at Month 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biogencell Ltd.

Sponsor organisation

Biogencell Ltd.

Address

16, Divrei Khayim

City

Netanya

Postcode

4244916

Country

Israel

Scientific contact point

Organisation

Biogencell Ltd.

Contact name

BioGenCell Contact

Public contact point

Organisation

Biogencell Ltd.

Contact name

BioGenCell Contact

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications