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The Efficacy and Safety of REX-001 to Treat Ischemic Ulcers in Subjects With CLI Rutherford Category 5 and DM

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ClinicalTrials.gov Identifier: NCT03174522
Recruitment Status : Recruiting
First Posted : June 2, 2017
Last Update Posted : August 31, 2018
Sponsor:
Collaborator:
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Information provided by (Responsible Party):
Rexgenero Limited

Tracking Information
First Submitted Date  ICMJE May 31, 2017
First Posted Date  ICMJE June 2, 2017
Last Update Posted Date August 31, 2018
Actual Study Start Date  ICMJE April 25, 2017
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2017)
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 Rexmyelocel-T or placebo.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03174522 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Efficacy and Safety of REX-001 to Treat Ischemic Ulcers in Subjects With CLI Rutherford Category 5 and DM
Official Title  ICMJE 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
Brief 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 limb.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Peripheral Arterial Disease (PAD)
  • Diabetes Mellitus (DM)
  • Diabetes Mellitus, Type 1
  • Diabetes Mellitus, Type 2
  • Cardiovascular Disease
  • Critical Limb Ischemia (CLI)
Intervention  ICMJE
  • Drug: REX-001
    REX-001 is administered through an intra-arterial catheter.
  • Drug: Placebo
    Placebo is administered through an intra-arterial catheter.
Study Arms  ICMJE
  • Experimental: REX-001
    REX-001 is a cell suspension of autologous bone marrow mononuclear cells (BM-MNCs) composed of several mature cell types.
    Intervention: Drug: REX-001
  • Placebo Comparator: Placebo
    The final formulation of the placebo will be a diluted suspension of red blood cells.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 1, 2017)
78
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2021
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  1. Aged ≥ 18 to ≤ 85 years.
  2. Diagnosis of Type I or II DM, established more than one year ago.
  3. Glycosylated hemoglobin (HbA1c) < 9%.
  4. 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
    • 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.

  5. 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.
  6. 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.

EXCLUSION CRITERIA:

Subjects meeting any of the following criteria must not be enrolled in the trial:

  1. 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.
  2. CLI Rutherford Category 4.
  3. Uncontrolled or untreated proliferative retinopathy.
  4. Failed surgical or endovascular revascularization on the index leg within 10 days after the procedure.
  5. 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).
  6. 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.
  7. At screening, the presence of only neuropathic ulcers on the index leg.
  8. Amputation at or above the talus on the index leg.
  9. Planned major amputation within the first month after randomization.
  10. 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.
  11. Blood clotting disorder not caused by medication (e.g., thrombophilia).
  12. Severe hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. (34)
  13. A platelet count < 50,000/μL.
  14. 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.
  15. Evidence of moderate to severe hepatocellular dysfunction according to the treating physician.
  16. Positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus (HBV), hepatitis C virus (HCV) or Treponema pallidum.
  17. 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:

    1. Concurrent severe congestive heart failure (New York Heart Association Classes III and IV).
    2. 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.
    3. Coronary artery bypass grafting or percutaneous coronary intervention within one month before screening.
    4. A renal and/or carotid revascularization procedure within one month of screening.
    5. Transient ischemic attack within three months prior to screening.
    6. Deep vein thrombosis within three months prior to screening.
    7. Subjects with immunocompromised conditions, organ transplant recipients and/or subjects in need of immunosuppressive therapy.
    8. Neurological dementia (i.e., Alzheimer's Disease).
  18. Subjects who participate in another clinical interventional trial.
  19. Subjects who have been treated with experimental medication within 30 days of screening.
  20. Subjects who participated in other cell therapy trials for CLI.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Edwin Wagena, PhD +31 6 15859687 edwin.wagena@rexgenero.com
Contact: Karen Reitsma, PhD karen.reitsma@rexgenero.com
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03174522
Other Study ID Numbers  ICMJE REX-001-004_CLI 5
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Rexgenero Limited
Study Sponsor  ICMJE Rexgenero Limited
Collaborators  ICMJE Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Investigators  ICMJE
Study Director: Edwin Wagena, PhD Rexgenero Limited
PRS Account Rexgenero Limited
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP