Clinical trial NCT06135103: Phase 2 Study of TXA127 in Post-ischemic Stroke Patients
Official title: A 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ischemic Stroke
Lead sponsor: Constant Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age: 18-85 years
2. BMI: 18.0-35.0 kg/m2
3. Patient suffered an ischemic stroke (caused by blockage of the middle cerebral artery) 6-24 months prior to enrollment and with no additional symptomatic stroke incidents since then.
4. Patient resides in Israel between Hedera and Gedera
5. Fugl-Meyer Assessment of Upper Extremity: 20-50 without reflex items
6. Patient suffers from hemiparesis as assessed by the study investigator
7. Premorbid disability does not impact physical and cognitive function to a degree that would limit completion of study activities and assessments, as assessed by the study investigator
8. Patient agrees to participate in two physical therapy or occupational therapy sessions per week
9. Patient is able to use a device for telemedicine meetings with a physician and to record study-related events in an electronic diary, either alone or with caregiver's assistance

Exclusion Criteria:

1. Woman of childbearing potential who is pregnant or planning to become pregnant, or not using birth control
2. Aphasia or dementia limiting ability of patient to comply with instructions as assessed by the study investigator
3. Current diagnosis of severe depression (NOTE: In case of doubt, a patient who is currently taking or has taken within the last 30 days second-line anti-depressants OR who has scored 12-15 points using the Geriatric Depression Scale, will be considered severely depressed and will not be eligible to participate in the study.)
4. Drug or alcohol abuse within the last year
5. Current or planned Botox administration for upper limb spasticity, strabismus, overactive bladder, migraine prevention, blepharospasm, cervical dystonia or other off-label uses including but not limited to: sialorrhea, post-herpetic neuralgia, Raynaud's disease, achalasia, or any use the investigator believes may interfere with an accurate neurological exam. Permitted uses - cosmetic (wrinkles), hyperhidrosis
6. Participation in a transcranial magnetic stimulation and/or other interventional stroke studies within 6 months of screening
7. History of cancer within three years of screening, with the exception of fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at least 6 months
8. Any medical condition that, in the opinion of the investigator, would preclude patient participation in the study and/or analysis of results
9. Significant disability prior to stroke that would impact execution of any of the functional assessments in the protocol

Primary outcomes:
measure: Fugl-Meyer Assessment of Upper Extremity (FM-UE)
timeFrame: 12 weeks
measure: Adverse Events
timeFrame: 12 weeks
Secondary outcomes:
measure: Fugl-Meyer Assessment of Lower Extremity (FMA-LE)
timeFrame: 12 weeks
measure: Time Up and Go
timeFrame: 12 weeks
measure: Stroke Impact Scale
timeFrame: 12 weeks
measure: Durability of Fugl-Meyer
timeFrame: 24 weeks
measure: Durability of Time Up and Go
timeFrame: 24 weeks
measure: Durability of Stroke Impact Scale
timeFrame: 24 weeks
Other outcomes:
measure: Brain-derived neurotrophic factor (BDNF)
timeFrame: 12 weeks
measure: Neurofilament light chain (NfL)
timeFrame: 12 weeks
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
References: