MTX-001 for the Treatment of Non-Healing Venous Stasis Ulcers

DL-VSU-201 is a multi-center, two-part study in patients with VSU (n=80). The lead-in phase of the study (Part 1) enrolled 11 eligible patients. In Part 1, patients were allocated to receive active MTX-001 once weekly or once every two weeks with standard of care. After completion of Part 1, the data was reviewed to determine the administration frequency of Study Product in Part 2 of the Study.

In Part 2, approximately 70 patients will be randomized 1:1 to receive MTX-001 or placebo (0.9% NaCl) with standard of care. Patients will be administered study treatment weekly, as needed.

Patients will receive localized subcutaneous injection of MTX-001 or placebo into and/or around the wound bed during weekly clinic visits over a 12-week period and assessed for safety and efficacy measures at Screening, Baseline, and Weeks 4, 8, and 12. Percent reduction of the wound surface area will be formally collected at Baseline, Weeks 4, 8, and 12. To assess healing, the ulcer will be evaluated by assessing the change in the surface area from Baseline. Overall change in VAS from Baseline to Week 12 will be evaluated and total wound closure will be evaluated at Week 12.

Inclusion criteria

• Patients who voluntarily give written informed consent to participate in study
• Males and female patients aged 18 to 75 years inclusive at Screening (date the patient provides written informed consent to participate in study) for Part 1 only
• Males and female patients aged 18 to 90 years inclusive at Screening (date the patient provides written informed consent to participate in study) for Part 2 only
• Patients having a full thickness ulcer that meets the following criteria:

• Ulcer surface area ≥ 4 cm2 and < 25 cm2
• Ulcer surface area hasn't increased or decreased by 40% or more, as assessed within 28 days prior to Baseline
• Ulcer depth ≥ 0.2 cm at the deepest point of the wound, as measured by gently inserting a pre-moistened cotton tipped applicator into the deepest part of the wound.
• Ulcer age < 36 months (1095 days) prior to Baseline (for Part 2 only)
• Received ≥ 28 days of standard, conventional wound therapy with a therapeutic high-compression (≥40 mmHg), multilayer bandaging (e.g. compression hose, custom garments, commercial kits, etc.) prior to the Baseline visit. If clinically necessary, patients may have received other wound treatments as needed (e.g., surgical debridement, pressure offloading, negative pressure and/or hyperbaric oxygen therapy).
• Patient must have previously undergone venous hemodynamic correction via therapeutic compression (≥40 mmHg), surgical venous stripping, sclerotherapy, endovenous laser ablation, and/or endovenous radiofrequency ablation.
• Patient must have adequate circulation to the affected extremity as demonstrated by the most recently measured ankle-brachial index (ABI) greater than or equal to 0.8 and less than or equal to 1.2 or triphasic or biphasic Doppler arterial waveforms at the ankle of the affected leg (as applicable). If patient has undergone lower extremity stenting or bypass where ABI would be considered unreliable to assess microvascular circulation, patients must have transcutaneous oximetry (TcPO2) > 40 mmHg.
• Patient must have VSU caused by underlying venous reflux disease with physiological reflux lasting greater than or equal to 500 milliseconds for superficial veins OR 1.0 seconds for deep veins, as confirmed by most recent Doppler ultrasound venous mapping from Baseline; historical results/confirmation within the previous three years allowed.
• Patients who agree to follow the specified precautions to avoid pregnancy as follows:

• Patients who are female of childbearing potential include any female patient who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months). For female patients of childbearing potential, a negative urine pregnancy test is required at Screening and Baseline prior to initiating Study Product. Female patients of childbearing potential must follow 1 of the following approaches:
• Practice actual abstinence from intercourse
• Have a partner with a vasectomy
• Have an intrauterine device
• Must use 2 different forms of highly effective contraception for the duration of the study, and for at least 48 hours after discontinuing study drug. Medically acceptable forms of effective contraception include approved hormonal contraceptives (such as birth control pills) or barrier methods (such as a condom or diaphragm).
• Male patients with a partner of childbearing potential must use a condom during intercourse for the duration of the study, and for 48 hours after discontinuing study drug.
• Patients who, in the opinion of the Investigator, are capable of communicating effectively with study personnel and are considered reliable, willing, and likely to be cooperative with protocol requirements and attend all required study visits.
• Patients who have the capability to answer surveys and questionnaires written in English.

Exclusion criteria

• Patient must not be currently receiving topical antimicrobials and ulcer must not be infected as determined by clinical assessment according to The International Wound Infection Institute (IWII) criteria (e.g. odor, color, visual appearance) rather than culture.
• Ulcer must not have exposed bone, tendon, or ligament.
• Patient must not have another ulcer within 2 cm from the ulcer receiving investigational treatment.
• Female patients who are pregnant, lactating, or planning to become pregnant during the study.
• Patients actively receiving or received any skin graft substitute within 30 days prior to Baseline.
• Patients receiving oral, systemically administered, or lower extremity injectable corticosteroid therapy within 60 days prior to Baseline.
• Patients with angiographic or clinical signs of peripheral arterial disease (PAD)
• Patients with underlying osteomyelitis.
• Patients with an active infection or condition that would interfere with interpretation of study assessments.
• Patients with an HbA1c > 7.0% (Part 1 only) or HbA1c > 10.0% (Part 2 only), as collected at Screening or in the previous 90 days prior to Screening.
• Patients with current deep vein thrombosis (DVT) (Part 2 only)
• Patients with chronic musculoskeletal disorder or any other disease that would limit ambulation.
• Patients with a history of alcohol abuse or illicit drug abuse within 6 months of Baseline which, in the Investigator's opinion, would make the patient inappropriate for enrollment in a clinical study.
• Patients with any other concomitant disease with life expectancy of <12 months from Baseline
• Patients with an unstable psychiatric condition or those not capable of understanding the objectives, nature, or consequences of the study, or who have any condition which, in the Investigator's opinion, would constitute an unacceptable risk to the patient's safety.
• Patients who are currently receiving an investigational drug, have an investigational device in place, or who have participated in an investigational drug or device study within 90 days prior to Baseline. Participation in an observational study within 90 days prior to Baseline does not disqualify a patient from enrolling.
• Patients who have received another regenerative therapy within 30 days prior to Baseline.
• Patients with a Body Mass Index (BMI) > 45 (Part 2 only) or other clinical symptoms (e.g. edema) that do not allow for adequate therapeutic compression.