Amyotrophic Lateral Sclerosis
Conditions
Keywords
regenerative, synapse, Amyotrophic Lateral Sclerosis, placebo-controlled
Brief summary
The objectives of this study are to examine the effects of tazbentetol on clinical measures of ALS, patient reported outcomes (PROs), long-term safety and tolerability.
Detailed description
This is a Phase 2B/3 adaptive design randomized, double-blind, placebo-controlled (DBPC) study to evaluate the efficacy, safety and tolerability of tazbentetol administered orally in participants with ALS. The study consists of 2 parts, as follows Phase 2 double-blind, placebo controlled (DBPC): Randomized, double-blind, placebo-controlled study. Participants will be randomized to receive tazbentetol or placebo for 36 weeks. Phase 3 double blind, placebo controlled (DBPC): Randomized, double-blind, placebo-controlled study. Participants will be randomized to receive the dose determined from Phase 2 or placebo for 36 weeks. Open-label extension: Eligible participants who complete 36 weeks in the DBPC of either Phase 2 or Phase 3 will be offered to enroll into the OLE, starting at the corresponding DBPC Week 36 visit, and receive tazbentetol for 36 weeks. The dose for this extension will be based on data from DBPC phases.
Interventions
DRUGTazbentetol
Participants in both Phase 2B and Phase 3 will be randomized to received study drug tazbentetol or placebo tablets. Participants in the open-label extension phase will receive the dose determined from Phase 2.
DRUGplacebo
participants in double blind placebo controlled phase will be randomized to received placebo tablets
Sponsors
Spinogenix
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-80 * ALS TRICALS risk score * Stable dose of standard of care treatment * Contraception use by men or women consistent with local regulations * Able and willing to provide written informed consent
Exclusion criteria
* Underlying physical or psychological condition prohibiting study completion * Clinically significant cardiac disease * Active or history of malignancy in the past 5 years * Serious infection within 1 month of screening * Acute illness within 30 days of Day 1 * History of suicidal behavior or suicidal ideation * Active cigarette smokers and users of nicotine-containing products * Neurodegenerative disease * External respiratory support or supplemental oxygen requirement * HIV, hepatitis B and hepatitis C positive * Vaccines within 14 days * Other investigational products within 30 days * Blood donation within 30 days * Plasma donation within 7 days * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Absolute change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) total score | 36 weeks | Questionnaire administered by a clinician that measures participants' ability to function in certain daily activities. Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Patients with higher scores have more physical function. |
| Phase 3: Absolute change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) total score | 36 weeks | Questionnaire administered by a clinician that measures participants' ability to function in certain daily activities. Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Patients with higher scores have more physical function. |
| OLE: Absolute change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) total score | 36 weeks | Questionnaire administered by a clinician that measures participants' ability to function in certain daily activities. Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Patients with higher scores have more physical function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Combined Assessment of Function and Survival (CAFS) scores | 36 weeks | This assessment ranks clinical outcome based on changes to ALSFRS-R score. A higher score indicates a better clinical outcome. |
| Phase 2: Change from baseline in Clinician Global Impression-Inhibitory (CGI-I) | 36 weeks | Change in clinician rated measures on scale of 1 to 7, higher value indicates more severe symptom presentation |
| Phase 2: Change from baseline in Edinburgh Cognitive and Behavioural ALS Screen (ECAS) | 36 weeks | Questionnaire to assesses cognitive and behavioral changes in people with (ALS) through a 136-point test covering language, verbal fluency, executive function, memory, and visuospatial cognitive domains. A lower score indicates worsening of symptoms. |
| Phase 2: Change from baseline in ALS Assessment Questionnaire 40 items (ALSAQ-40) | 36 weeks | The ALSAQ40 score is a measure of QoL for patients with ALS. The ALSAQ40 evaluates domains that include physical mobility, activities of daily living (ADL) and independence, eating and drinking, communication, and emotional reactions. A higher score indicates higher disability. |
| Phase 2: Change from baseline in Patient Global Impression (PGI) of Improvement | 36 weeks | This will measure all aspects of patient health and improvement or decline. A higher scale indicates greater disability. |
| Phase 2: Change from baseline in Rasch Overall ALS Disability (ROADS). | 36 weeks | This will measure patient reported outcomes of overall disability. A lower score indicates greater disability. |
| Phase 2: Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) | 36 weeks | This will assess the safety and tolerability of tazbentetol in of participants with ALS |
| Phase 3: Combined Assessment of Function and Survival (CAFS) scores | 36 weeks | This assessment ranks clinical outcome based on changes to ALSFRS-R score. A higher score indicates a better clinical outcome. |
| Phase 3: Change from baseline in Clinician Global Impression-Inhibitory (CGI-I) | 36 weeks | Change in clinician rated measures on scale of 1 to 7, higher value indicates more severe symptom presentation |
| Phase 3: Change from baseline in Edinburgh Cognitive and Behavioural ALS Screen (ECAS) | 36 weeks | Questionnaire to assesses cognitive and behavioral changes in people with (ALS) through a 136-point test covering language, verbal fluency, executive function, memory, and visuospatial cognitive domains. A lower score indicates worsening of symptoms. |
| Phase 3: Change from baseline in ALS Assessment Questionnaire 40 items (ALSAQ-40) | 36 weeks | The ALSAQ40 score is a measure of QoL for patients with ALS. The ALSAQ40 evaluates domains that include physical mobility, activities of daily living (ADL) and independence, eating and drinking, communication, and emotional reactions. A higher score indicates higher disability. |
| Phase 3: Change from baseline in Patient Global Impression (PGI) of Improvement | 36 weeks | This will measure all aspects of patient health and improvement or decline. A higher scale indicates greater disability. |
| Phase 3: Change from baseline in Rasch Overall ALS Disability (ROADS). | 36 weeks | This will measure patient reported outcomes of overall disability. A lower score indicates greater disability. |
| Phase 3: Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) | 36 weeks | This will assess the safety and tolerability of tazbentetol in of participants with ALS |
| OLE: Combined Assessment of Function and Survival (CAFS) scores | 36 weeks | This assessment ranks clinical outcome based on changes to ALSFRS-R score. A higher score indicates a better clinical outcome. |
| OLE: Change from baseline in Clinician Global Impression-Inhibitory (CGI-I) | 36 weeks | Change in clinician rated measures on scale of 1 to 7, higher value indicates more severe symptom presentation |
| OLE: Change from baseline in ALS Assessment Questionnaire 40 items (ALSAQ-40) | 36 weeks | The ALSAQ40 score is a measure of QoL for patients with ALS. The ALSAQ40 evaluates domains that include physical mobility, activities of daily living (ADL) and independence, eating and drinking, communication, and emotional reactions. A higher score indicates higher disability. |
| OLE: Change from baseline in Edinburgh Cognitive and Behavioural ALS Screen (ECAS) | 36 weeks | Questionnaire to assesses cognitive and behavioral changes in people with (ALS) through a 136-point test covering language, verbal fluency, executive function, memory, and visuospatial cognitive domains. A lower score indicates worsening of symptoms. |
| OLE: Change from baseline in Patient Global Impression (PGI) of Improvement | 36 weeks | This will measure all aspects of patient health and improvement or decline. A higher scale indicates greater disability. |
| OLE: Change from baseline in Rasch Overall ALS Disability (ROADS). | 36 weeks | This will measure patient reported outcomes of overall disability. A lower score indicates greater disability. |
| OLE: Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) | 36 weeks | This will assess the safety and tolerability of tazbentetol in of participants with ALS |
Contacts
CONTACTStudy Contact
Outcome results
None listed