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This is a 50-patient, Phase 2, double-blind, randomized, placebo-controlled, hybrid decentralized study to evaluate the safety and efficacy of daily subcutaneous (SC) injection of TXA127 in post-ischemic stroke patients. Subjects will receive either TXA127 0.5mg/kg or placebo for 12 weeks started 6 to 24 months post ischemic stroke, and they will have a 12 week follow up visit after treatment has ended. The primary efficacy outcome measure is individual patient absolute change from baseline in motor and sensory functions as measured by the Fugl-Meyer Assessment of Upper Extremity (FMA-UE) 12 weeks after start of treatment.
This is a safety, tolerability, and efficacy study in patients with sensorimotor deficits after confirmed middle cerebral artery ischemic stroke. The study will be double-blinded and placebo-controlled and conducted over a period of approximately 6 months, with treatment starting 6-24 months after stroke. After obtaining informed consent, eligibility will be determined by review of medical history and assessments of patient's condition. To establish a baseline, all assessments will be completed prior to administration of the first dose of study drug.
Patients will be randomized (1:1) to receive either subcutaneous (SC) placebo or TXA127 (0.5 mg/kg) injections once daily for 12 weeks. In addition to receiving either the study drug or placebo, patients will be required to undergo physical therapy (PT) or occupational therapy (OT) at least twice a week. Patients will be followed up for 12 weeks after end of treatment.
Throughout the study, study visits will be conducted at the medical center and the patient's home. At certain planned study visits, patients will undergo a brief physical examination, and blood will be drawn for safety evaluation and for measuring biomarkers. At the Screening, Week 12, and Week 24 visits, patients will rate their disability and health-related quality of life using the Stroke Impact Scale. In addition, upper and lower extremity motor and sensory function (FMA-UE/LE), and gait velocity (Timed Up and Go) will be evaluated. Patients will be asked to report of any safety events throughout the study and follow up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| talfirastide (TXA127) | Experimental | TXA127 will be given daily for 12 weeks at a dose of 0.5.mg/kg via SC injection. |
|
| placebo | Placebo Comparator | Placebo will be given daily for 12 weeks via SC injection. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| talfirastide | Drug | TXA127, a pharmaceutically formulated angiotensin (1-7) heptapeptide, identical to the endogenously produced, non-hypertensive derivative of angiotensin II (Ang II) is a sterile solution containing angiotensin (1-7) [A(1-7)], supplied in a 3 mL, single-use, stoppered vial. |
| Measure | Description | Time Frame |
|---|---|---|
| Fugl-Meyer Assessment of Upper Extremity (FM-UE) | Individual patient absolute change from baseline in motor and sensory functions as measured by the Fugl-Meyer Assessment of Upper Extremity (FMA-UE) 12 weeks after start of treatment. | 12 weeks |
| Adverse Events | Incidence of adverse events (AEs) assessed according to CTCAE v5.0 | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Fugl-Meyer Assessment of Lower Extremity (FMA-LE) | Individual patient absolute change from baseline in motor and sensory functions as measured by the Fugl-Meyer Assessment of Lower Extremity (FMA-LE) 12 weeks after start of treatment. | 12 weeks |
| Time Up and Go |
| Measure | Description | Time Frame |
|---|---|---|
| Brain-derived neurotrophic factor (BDNF) | change in serum brain-derived neurotrophic factor | 12 weeks |
| Neurofilament light chain (NfL) | change in serum neurofilament light chain |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Richard L Franklin, MD, PhD | Contact | 1-617-245-0289 | 101 | rfranklin@constanttherapeutics.com |
| Elizabeth Wagner, MS, MBA | Contact | 1-617-245-0289 | 102 | ewagner@constanttherapeutics.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sheba Medical Center | Recruiting | Ramat Gan | Israel |
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C118790 | angiotensin I (1-7) |
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|
|
| Placebo | Drug | Placebo is a sterile solution containing supplied in a 3 mL, single-use, stoppered vial. |
|
Percent change from baseline gait velocity as measured by Timed Up and Go 12 weeks after start of treatment |
| 12 weeks |
| Stroke Impact Scale | Absolute change from patient's baseline self-assessment as measured by Stroke Impact Scale 12 weeks after start of treatment, scored 0 to 100 with higher scores indicating higher quality of life | 12 weeks |
| Durability of Fugl-Meyer | Absolute change in motor and sensory function as measured by the Fugl-Meyer Assessment of Upper and lower Extremity (FMA-UE & FMA-LE) | 24 weeks |
| Durability of Time Up and Go | Percent change in gait velocity as measured by Timed Up and Go | 24 weeks |
| Durability of Stroke Impact Scale | Absolute change in patient self-assessment as measured by Stroke Impact Scale over the 12-week follow-up period (12-24 weeks after the start of treatment); scored 0 to 100 with higher scores indicating higher quality of life | 24 weeks |
| 12 weeks |
| D009422 |
| Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |