Efficacy and Safety of Tazbentetol in ALS Participants

A Phase 2B/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Tazbentetol in Participants With Amyotrophic Lateral Sclerosis (ALS)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: placebo; Drug: Tazbentetol

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.

• Study Type: Interventional
• Enrollment (Estimated): 430
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 503 915 1400; Email: contact@spinogenix.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Drug: placebo; participants in double blind placebo controlled phase will be randomized to received placebo tablets
Experimental: tazbentetol; synthetic small molecule	Drug: Tazbentetol; 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.; Other Names: SPG302

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Absolute change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) total score	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.	36 weeks
Phase 3: Absolute change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) total score	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.	36 weeks
OLE: Absolute change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) total score	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.	36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Combined Assessment of Function and Survival (CAFS) scores	This assessment ranks clinical outcome based on changes to ALSFRS-R score. A higher score indicates a better clinical outcome.	36 weeks
Phase 2: Change from baseline in Clinician Global Impression-Inhibitory (CGI-I)	Change in clinician rated measures on scale of 1 to 7, higher value indicates more severe symptom presentation	36 weeks
Phase 2: Change from baseline in Edinburgh Cognitive and Behavioural ALS Screen (ECAS)	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.	36 weeks
Phase 2: Change from baseline in ALS Assessment Questionnaire 40 items (ALSAQ-40)	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.	36 weeks
Phase 2: Change from baseline in Patient Global Impression (PGI) of Improvement	This will measure all aspects of patient health and improvement or decline. A higher scale indicates greater disability.	36 weeks
Phase 2: Change from baseline in Rasch Overall ALS Disability (ROADS).	This will measure patient reported outcomes of overall disability. A lower score indicates greater disability.	36 weeks
Phase 2: Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)	This will assess the safety and tolerability of tazbentetol in of participants with ALS	36 weeks
Phase 3: Combined Assessment of Function and Survival (CAFS) scores	This assessment ranks clinical outcome based on changes to ALSFRS-R score. A higher score indicates a better clinical outcome.	36 weeks
Phase 3: Change from baseline in Clinician Global Impression-Inhibitory (CGI-I)	Change in clinician rated measures on scale of 1 to 7, higher value indicates more severe symptom presentation	36 weeks
Phase 3: Change from baseline in Edinburgh Cognitive and Behavioural ALS Screen (ECAS)	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.	36 weeks
Phase 3: Change from baseline in ALS Assessment Questionnaire 40 items (ALSAQ-40)	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.	36 weeks
Phase 3: Change from baseline in Patient Global Impression (PGI) of Improvement	This will measure all aspects of patient health and improvement or decline. A higher scale indicates greater disability.	36 weeks
Phase 3: Change from baseline in Rasch Overall ALS Disability (ROADS).	This will measure patient reported outcomes of overall disability. A lower score indicates greater disability.	36 weeks
Phase 3: Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)	This will assess the safety and tolerability of tazbentetol in of participants with ALS	36 weeks
OLE: Combined Assessment of Function and Survival (CAFS) scores	This assessment ranks clinical outcome based on changes to ALSFRS-R score. A higher score indicates a better clinical outcome.	36 weeks
OLE: Change from baseline in Clinician Global Impression-Inhibitory (CGI-I)	Change in clinician rated measures on scale of 1 to 7, higher value indicates more severe symptom presentation	36 weeks
OLE: Change from baseline in ALS Assessment Questionnaire 40 items (ALSAQ-40)	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.	36 weeks
OLE: Change from baseline in Edinburgh Cognitive and Behavioural ALS Screen (ECAS)	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.	36 weeks
OLE: Change from baseline in Patient Global Impression (PGI) of Improvement	This will measure all aspects of patient health and improvement or decline. A higher scale indicates greater disability.	36 weeks
OLE: Change from baseline in Rasch Overall ALS Disability (ROADS).	This will measure patient reported outcomes of overall disability. A lower score indicates greater disability.	36 weeks
OLE: Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)	This will assess the safety and tolerability of tazbentetol in of participants with ALS	36 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: ALSFRS-R total score rate of decline	To further assess the effect of tazbentetol on the progression of ALS	36 weeks
Phase 2: Proportion of patients alive and survival time	To further assess the effect of tazbentetol on the progression of ALS	36 weeks
Phase 2 substudy: To compare electroencephalogram (EEG) outcomes of two dose levels of tazbentetol to placebo in participants with ALS	To measure the change from baseline in EEG delta and power bands at resting state at Weeks 8, 24, and 36	36 weeks
Phase 3: ALSFRS-R total score rate of decline	To further assess the effect of tazbentetol on the progression of ALS	36 weeks
Phase 3: Proportion of patients alive and survival time	To further assess the effect of tazbentetol on the progression of ALS	36 weeks
OLE: ALSFRS-R total score rate of decline	To further assess the effect of tazbentetol on the progression of ALS	36 weeks
OLE: Proportion of patients alive and survival time	To further assess the effect of tazbentetol on the progression of ALS	36 weeks

Collaborators and Investigators

• Sponsor: Spinogenix

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: January 6, 2026
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; placebo-controlled; regenerative; synapse
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: SPG302-ALS-003 (SPARK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No