Autologous Stem Cells for the Treatment of No Option Critical Limb Ischemia

NCT03455335 | Completed Phase 1 DMC

• 1 other identifier: 2013-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The trial is a phase 1b, open label, uncontrolled, non-randomized dose-escalation study of autologous bone marrow-derived MSCs. Following informed consent, patients who meet the criteria will be screened and enrolled. Up to 100 mls of bone marrow will be harvested from the participant from which MSCs will be culture expanded. In this dose escalation study, 3 participants on each cohort will be treated with a targeted dose of either 20 million hMSC; 40 million hMSC; or 80 million hMSC. The cells will be administered to the ischemic leg by 20 intramuscular injections of approximately 0.5ml per injection . Treatment groups will be completed sequentially, beginning with the lowest dose group.

Conditions

Critical Limb Ischemia

Outcome Measures

Primary Outcomes (2)

• The number of Serious Adverse Events that are attributable to the treatment

  The number of Serious Adverse Events that are attributable to the MScs

  12 months

• The severity of Serious Adverse Events that are attributable to the treatment

  The number of Serious Adverse Events that are attributable to the MScs

  12 months

Secondary Outcomes (8)

• Amputation free survival

  12 months

• median time to amputation,

  12 months

• Change in Transcutaneous Pressure of Oxygen TcPO2

  12 months

• Change in Ankle Brachial Index

  12 months

• Collateral vessel formation

  12 months

Study Arms (3)

low dose cohort

EXPERIMENTAL

20 million hMSCs .

Drug: 20 million hMSCs

mid dose cohort

EXPERIMENTAL

40 million hMSCs

Drug: 40 million hMSCs

high dose cohort

EXPERIMENTAL

80 million hMSCs .

Drug: 80 million hMSCs

Interventions

20 million hMSCs DRUG

Also known as: 20 million hMSCs intramuscularly

low dose cohort

40 million hMSCs DRUG

Also known as: 40 million hMSCs intramuscularly

mid dose cohort

80 million hMSCs DRUG

Also known as: 80 million hMSCs intramuscularly

high dose cohort

Eligibility Criteria

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

You may qualify if:

• Men and women between the ages of 18 and 85
• Voluntary written informed consent, given before performance of any study-related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care
• Presented with CLI with rest pain or ulceration with no option for revascularization agreed by an expert panel including an interventional radiologist and vascular surgeon; CLI defined as persistent ischemic rest pain for greater than or equal to 2 weeks and/or ulceration or gangrene of the toe or foot
• Estimated life expectancy \> 6 months as deemed by patient's clinician and/or investigator
• Suitable candidate for a bone marrow aspiration, deemed by Consultant Haematologist
• Chronic critical limb ischaemia with rest pain (Rutherford Class 4) or mild-to-moderate tissue loss (Rutherford Class 5) who are not candidates for revascularisation
• Medically fit to undergo bone marrow harvest and stem cell intramuscular injection
• One of the following haemodynamic parameters: ankle systolic pressure \< 70 mmHg or ABI \<0.9 TBI \<0 .6 TcPO2 \<60mmHg on room air

You may not qualify if:

• Has received prior therapy with MSCs
• Has had previous amputation of the talus or above
• Has failed revascularization within 2 weeks before entry to the study
• Known Aortoiliac disease with \> 50% stenosis
• Contraindication to intramuscular procedure, including active infection in the affected limb, or wet gangrene or exposed bone or tendon in lower limb with CLI, or in the opinion of the attending clinician, is unsuitable for intramuscular procedure
• Severe co-morbidity limiting 6 month survival of patients
• Abnormal liver function as defined by AST and ALT \> 2.5 fold the ULN and total bilirubin \> 1.5 ULN
• Significant cognitive impairment (Mini Mental Status Examination \<22)
• Presence of proliferative retinopathy (in participants with diabetes mellitus only)
• Presence of poorly controlled diabetes mellitus with HbAIc \> 10% within previous 3 months
• HIV or HBsAg positive
• Presence of acute coronary syndrome
• Patient has known active malignancy
• Pregnancy
• Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel

Sponsors & Collaborators

• National University of Ireland, Galway, Ireland: lead
• University Hospital of Limerick: collaborator

Study Sites (1)

Galway University Hospital

Galway, Galway, 0, Ireland

Location

Related Publications (2)

• Mohamed SA, Howard L, McInerney V, Hayat A, Krawczyk J, Naughton S, Finnerty A, Holohan M, Duffy A, Moloney T, Kavanagh E, Burke P, Liew A, Tubassam M, Walsh SR, O'Brien T. Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities. Cytotherapy. 2020 Jun;22(6):313-321. doi: 10.1016/j.jcyt.2020.02.007. Epub 2020 Apr 6.

  PMID: 32273232 BACKGROUND

• EU Clinical Trials Register Clinical trial results 2013-003447-37 version 1 EU-CTR publication date: of 21 01 January 2021

  BACKGROUND

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

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

Study Officials

• Timothy O Brien, PhD

  NUIG

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Tim o Brien

Model Details: Advanced Therapeutic Medicinal Product ( ATMP) Bone Marrow Derived Mesenchymal Stem Cells

Study Record Dates

• First Submitted: February 16, 2018
• First Posted: March 6, 2018
• Study Start: March 23, 2015
• Primary Completion: October 31, 2019
• Study Completion: October 31, 2019
• Last Updated: March 4, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)