Peripheral Arterial Disease (PAD)Phase 3NCT03174522
The Efficacy and Safety of REX-001 to Treat Ischemic Ulcers in Subjects With CLI Rutherford Category 5 and DM
A Phase 3 study testing REX-001 in people with Peripheral Arterial Disease (PAD) and Diabetes Mellitus (DM), run by Ixaka Ltd at 15 sites in 6 countries.
Trial summary
This trial is a pivotal, placebo-controlled, double-blind, parallel-group, adaptive trial conducted in subjects with DM and CLI Rutherford Category 5. Minimisation will be used to assign eligible subjects in a 2:1 ratio to receive a single intra-arterial administration of REX-001 or matching placebo into the index… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Peripheral Arterial Disease (PAD), Diabetes Mellitus (DM), Diabetes Mellitus, Type 1
- What is being tested?
- REX-001
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 15 sitesin 6 countries
- Study dates
- 25 Apr 2017to 13 Feb 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥ 18 to ≤ 85 years.
- Diagnosis of Type I or II DM, established more than one year ago.
- Glycosylated hemoglobin (HbA1c) < 9%.
- Subjects with poor or no (surgical or endovascular) revascularization option classified as CLI Rutherford Category 5. For these patients, one of the following must be confirmed and documented at screening:
- Ankle systolic pressure < 70 mmHg, or
- Toe systolic pressure < 50 mmHg, or
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- TcpO2 < 30 mmHg (lying down). Subjects with non-compressible or calcified vessels must qualify on toe pressure or tcpO2.
- Poor or no revascularization option means that, in the opinion of the Investigator, revascularization using surgical or endovascular methods are not feasible due to for example the anatomy of existing vessels and/or existing comorbidity and/or previously failed surgical or endovascular revascularization.
- In the opinion of the Investigator, the subject is controlled on medical therapy indicated for CLI (unless there is a documented contraindication or intolerance) and pain management is optimized.
- Women of childbearing potential must have a negative pregnancy test at screening. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. Men and women who are sexually active shall use effective contraceptive methods for the duration of their participation in this study if the partner of the male participant, or if the female participant is of childbearing potential. Effective contraceptive methods are e.g.:
- 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,
- Vasectomised partner, or
- Sexual abstinence. The use of this contraceptive method should be continued for at least the duration of participation in the study, and should be continued thereafter as long as indicated by the study doctor.
Who cannot join
- Subjects meeting any of the following criteria must not be enrolled in the trial:
- Advanced CLI defined as presence of major tissue loss as significant ulceration/gangrene proximal to the metatarsal heads (CLI Rutherford Category 6). Significant ulceration/gangrene means any ulceration that extends beyond the subcutaneous tissue layer, or any gangrene or tissue necrosis proximal to the metatarsal heads.
- CLI Rutherford Category 4.
- Uncontrolled or untreated proliferative retinopathy.
- Failed surgical or endovascular revascularization on the index leg within 10 days after the procedure.
- Subjects in whom arterial insufficiency in the lower extremity is the result of acute limb ischemia or an immunological or inflammatory or non-atherosclerotic disorder (e.g., thromboangiitis obliterans (Buerger's Disease), systemic sclerosis (both limited and diffuse forms).
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- Clinical evidence of invasive infection on index leg defined as major tissue loss at the mid-foot or heel involving tendon and/or bone, and/or when intravenous antibiotics are required to treat the infection according to the Investigator.
- At screening, the presence of only neuropathic ulcers on the index leg.
- Amputation at or above the talus on the index leg.
- Planned major amputation within the first month after randomization.
- 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, nonstandard-of-care treatments to the index leg during the trial.
- Blood clotting disorder not caused by medication (e.g., thrombophilia).
- Severe hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. (34)
- A platelet count < 50,000/μL.
- International normalized ratio (INR) > 1.5. For patients on anticoagulant medication an INR > 1.5 is allowed, provided that the Investigator and the haematologist consider the patient eligible to collect BM.
- Evidence of moderate to severe hepatocellular dysfunction according to the treating physician.
- 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 including BM collection, or who are not expected to survive more than 12 months, or in whom results may be particularly difficult to assess, as assessed by the Investigator. For example:
- Concurrent severe congestive heart failure (New York Heart Association Classes III and IV).
- Life-threatening ventricular arrhythmias, unstable angina (characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration), and/or myocardial infarction within four weeks before screening.
- Coronary artery bypass grafting or percutaneous coronary intervention within one month before screening.
- A renal and/or carotid revascularization procedure within one month of screening.
- Transient ischemic attack within three months prior to screening.
- Deep vein thrombosis within three months prior to screening.
- Subjects with immunocompromised conditions, organ transplant recipients and/or subjects in need of immunosuppressive therapy.
- Neurological dementia (i.e., Alzheimer's Disease).
- Subjects who participate in another clinical interventional trial.
- Subjects who have been treated with experimental medication within 30 days of screening.
- Subjects who participated in other cell therapy trials for CLI.
Trial locations and contacts
15 sites in 6 countries.
15 sites in 6 countries
Spain7 sites
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona
Hospital Universitari Vall d'Hebron
Barcelona
Hospital Universitario Puerta del Mar
Cadiz
First site: Hospital Universitario Reina Sofía
Córdoba
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona
Hospital Regional Universitario
Málaga
Hospital General Universitario Morales Meseguer
Murcia
Portugal3 sites
Hospital Garcia de Orta, EPE
Almada
Centro Hospitalar Lisboa Norte, EPE
Lisbon
Centro Hospitalar de São João
Porto
Netherlands2 sites
Leids Universitair Medisch Centrum
Leiden
Maastricht Universitair Medisch Centrum
Maastricht
About this study
Official title: The Efficacy and Safety of Intra-arterial Administration of REX-001 to Treat Ischemic Ulcers in Subjects With Critical Limb Ischemia (CLI) Rutherford Category 5 and Diabetes Mellitus: A Pivotal, Placebo-controlled, Double-blind, Parallel-group, Adaptive Trial
This trial is a pivotal, placebo-controlled, double-blind, parallel-group, adaptive trial conducted in subjects with DM and CLI Rutherford Category 5. Minimisation will be used to assign eligible subjects in a 2:1 ratio to receive a single intra-arterial administration of REX-001 or matching placebo into the index limb.
- Conditions
- Peripheral Arterial Disease (PAD), Diabetes Mellitus (DM), Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Cardiovascular Disease, Critical Limb Ischemia (CLI)
- Being tested
- REX-001, Placebo
- Keywords
- Autologous, Bone Marrow-derived Mononuclear Cells (BM-MNCs), Advanced Therapy Medicinal Product (ATMP), Tissue-engineered Medicinal Product, Revascularization, Angiogenesis, Vasculogenesis, Arteriogenesis
- Medical subject headings
- Peripheral Arterial Disease, Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Chronic Limb-Threatening Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REX-001Drug
REX-001 is administered through an intra-arterial catheter.
PlaceboDrug
Placebo is administered through an intra-arterial catheter.
| Study group | Role | What they receive |
|---|---|---|
| REX-001 | Experimental | REX-001 is a cell suspension of autologous bone marrow mononuclear cells (BM-MNCs) composed of several mature cell types. Receives: Drug: REX-001 |
| Placebo | Placebo comparator | The final formulation of the placebo will be a diluted suspension of red blood cells. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete healing of all ischemic ulcers on the index leg.
Change in Rutherford classification from CLI Category 5 to Category 4 or lower 12 months. after administration of REX-001 or placebo.
Measured: The primary endpoint for this trial will be assessed at 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2017
- Study start25 Apr 2017
- Primary completion13 Feb 2023
- Study completion13 Feb 2023
Why it stopped: Independent Data Monitoring Committee recommendation to stop due to futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Arterial Disease (PAD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ixaka Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Andalusian Network for Design and Translation of Advanced Therapies
- Responsible party
- Sponsor
- Investigators
- Gilbert Wagener, MD, Study director, Ixaka Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03174522
- Sponsor's protocol ID
- REX-001-005
- Status last verified
- Mar 2023
- First submitted
- 31 May 2017
- Last updated
- 16 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Intra-arterial Administration of REX-001 to Treat Ischemic Ulcers in Subjects With Critical Limb Ischemia (CLI) Rutherford Category 5 and Diabetes Mellitus: A Pivotal, Placebo-controlled, Double-blind, Parallel-group, Adaptive Trial
- ClinicalTrials.gov ID
- NCT03174522
- Acronym / sponsor ID
- REX-001-005
- Conditions
- Peripheral Arterial Disease (PAD), Diabetes Mellitus (DM), Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Cardiovascular Disease, Critical Limb Ischemia (CLI)
- Keywords
- Autologous, Bone Marrow-derived Mononuclear Cells (BM-MNCs), Advanced Therapy Medicinal Product (ATMP), Tissue-engineered Medicinal Product, Revascularization, Angiogenesis, Vasculogenesis, Arteriogenesis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Independent Data Monitoring Committee recommendation to stop due to futility
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Ixaka LtdIndustry (pharma, biotech, devices)
- Collaborators
- Andalusian Network for Design and Translation of Advanced Therapies
- Study start
- 25 Apr 2017 (actual)
- Primary completion
- 13 Feb 2023 (actual)
- Study completion
- 13 Feb 2023 (actual)
- First posted
- 2 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is a pivotal, placebo-controlled, double-blind, parallel-group, adaptive trial conducted in subjects with DM and CLI Rutherford Category 5. Minimisation will be used to assign eligible subjects in a 2:1 ratio to receive a single intra-arterial administration of REX-001 or matching placebo into the index limb.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| REX-001 | Experimental | Drug: REX-001REX-001 is a cell suspension of autologous bone marrow mononuclear cells (BM-MNCs) composed of several mature cell types. |
| Placebo | Placebo comparator | Drug: PlaceboThe final formulation of the placebo will be a diluted suspension of red blood cells. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Aged ≥ 18 to ≤ 85 years.
- Diagnosis of Type I or II DM, established more than one year ago.
- Glycosylated hemoglobin (HbA1c) < 9%.
- Subjects with poor or no (surgical or endovascular) revascularization option classified as CLI Rutherford Category 5. For these patients, one of the following must be confirmed and documented at screening:
- Poor or no revascularization option means that, in the opinion of the Investigator, revascularization using surgical or endovascular methods are not feasible due to for example the anatomy of existing vessels and/or existing comorbidity and/or previously failed surgical or endovascular revascularization.
Key exclusion criteria (29 listed)
- Advanced CLI defined as presence of major tissue loss as significant ulceration/gangrene proximal to the metatarsal heads (CLI Rutherford Category 6). Significant ulceration/gangrene means any ulceration that extends beyond the subcutaneous tissue layer, or any gangrene or tissue necrosis proximal to the metatarsal heads.
- CLI Rutherford Category 4.
- Uncontrolled or untreated proliferative retinopathy.
- Failed surgical or endovascular revascularization on the index leg within 10 days after the procedure.
- Subjects in whom arterial insufficiency in the lower extremity is the result of acute limb ischemia or an immunological or inflammatory or non-atherosclerotic disorder (e.g., thromboangiitis obliterans (Buerger's Disease), systemic sclerosis (both limited and diffuse forms).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| REX-001REX-001 is administered through an intra-arterial catheter. | Drug | REX-001 |
| PlaceboPlacebo is administered through an intra-arterial catheter. | Drug | Placebo |
Primary outcome
Complete healing of all ischemic ulcers on the index leg.
Time frame: The primary endpoint for this trial will be assessed at 12 months.
Change in Rutherford classification from CLI Category 5 to Category 4 or lower 12 months. after administration of REX-001 or placebo.
Results and safety
The study was stopped early (reason given: Independent Data Monitoring Committee recommendation to stop due to futility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilbert Wagener, MD study director
Ixaka Limited
15 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing REX-001 in people with Peripheral Arterial Disease (PAD) and Diabetes Mellitus (DM), run by Ixaka Ltd at 15 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Spain, Portugal, Netherlands, Czechia, Hungary and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Independent Data Monitoring Committee recommendation to stop due to futility). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete healing of all ischemic ulcers on the index leg. (time frame: The primary endpoint for this trial will be assessed at 12 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2023.