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This is a study of Kamlanoflast in patients with ALS. Kamlanoflast is orally administered over 24 weeks. Its effects on inflammatory and functional parameters will be studied. Information on safety and tolerability will be collected.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Cohort A | Experimental | Low dose Kamlanoflast by oral administration |
|
| Dose Cohort B | Experimental | High dose Kamlanoflast by oral administration |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kamlanoflast | Drug | Low dose Kamlanoflast by oral administration |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety] | Safety: Defined as the occurrence of serious and non-serious treatment-emergent adverse events (TEAEs) and clinically significant treatment-emergent abnormalities in clinical and laboratory values, in ALS subjects treated with study treatment. | From drug initiation through study completion, an average of 28 weeks |
| Incidence of Completing Study Treatment [Tolerability] | Tolerability: Defined as percentage of ALS subjects who complete the 24 weeks of study treatment (survival), without study drug-attributed intolerable AEs that lead to early permanent drug discontinuation. | From drug initiation through study completion, an average of 24 weeks |
| Biological Efficacy | Biological Efficacy: Changes from baseline over 24 weeks (longitudinal assessments) in blood neuroinflammatory marker levels following oral study drug treatment. | From enrollment through the end of study treatment at the Week 24 visit (longitudinal assessments) |
| ALS Functional Rating Scale Revised (ALSFRS-R) total and sub-domain scores | Changes from baseline over 6 month period (longitudinal monthly assessments) in ALS Functional Rating Scale Revised (ALSFRS-R) total and sub-domain scores. The 12 domains included in the ALSFRS-R are rated on a 5-point scale, 0 to 4, with a maximum score of 48 indicating the highest level of functioning. | From enrollment to the end of study treatment at the Week 24 Visit (longitudinal assessments) |
| Slow vital capacity (SVC) | Changes from baseline over 24 weeks in SVC (longitudinal assessments). | From enrollment to the end of study treatment at the Week 24 Visit (longitudinal assessments) |
| Measure | Description | Time Frame |
|---|---|---|
| Systemic Exposure | Systemic Exposure: Defined as blood study drug level measurement over 24 weeks of treatment (longitudinal assessments). | From enrollment to end of study treatment at the Week 24 Visit (longitudinal assessments) |
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Inclusion Criteria:
i. a reduction of 0.5 points per month or greater on the ALS Functional Rating Scale-Revised (ALSFRS-R), which will be calculated based on (most recent ALSFRS-R at least 12 weeks from screening - ALSFRS-R at screening)/time interval; or ii. a calculated progression rate: (48 - ALSFRS-R at "time of diagnosis") / duration from onset to diagnosis (month) that is 0.5 points per month or greater.
e) Plasma NfL levels ≥ 2 times the upper limit of the age-specific reference values for normal at the measuring laboratory at screening.
f) Capable of providing informed consent. g) Capable and willing to follow study protocol. h) Ability to swallow pills and liquids at the time of the screening visit and, in the investigator's opinion have the ability to swallow for the duration of the study OR can be fed via a Gastrostomy (G) tube or Percutaneous Endoscopic capacity (PEG) tube.
i) Slow vital capacity (SVC) > 65% of predicted value for gender, height, and age (participants perform SVC for three trials and the best SVC will be used).
j) Females of childbearing potential must agree to abstain from sex or use adequate method of contraception for the duration of the study period and for 28 days after the last dose of study drug.
k) Males must agree to abstain from sex or use adequate method of contraception for the duration of the study period and for 28 days after the last dose of study drug.
l) If an approved therapy for ALS is used during the study, a steady dose must be used as follows: i. Participants who do not currently receive riluzole and do not plan to receive riluzole during the study period. Participants receiving riluzole are on a stable dose for at least 4 weeks before enrollment. Participants receiving riluzole are expected to remain on the same dose throughout the duration of the study.
ii. Participants who do not currently receive edaravone and do not plan to receive edaravone during the study period. Participants receiving edaravone must have completed at least 1 cycle of treatment before enrollment and are expected to continue edaravone treatment throughout the duration of the study.
Exclusion Criteria:
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| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| D016472 | Motor Neuron Disease |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
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| Kamlanoflast |
| Drug |
High dose Kamlanoflast by oral administration |
|
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |