Amyotrophic Lateral Sclerosis
Conditions
Brief summary
A phase 2 double-blind, placebo-controlled study of AL001 in participants with C9orf72-associated ALS.
Detailed description
This is a phase 2 double-blind, placebo-controlled trial to test the safety, tolerability, pharmacokinetics, and pharmacodynamics of AL001 in participants with C9orf72-associated Amyotrophic Lateral Sclerosis.
Interventions
DRUGAL001
Administered via intravenous (IV) infusion
DRUGPlacebo
Administered via intravenous (IV) infusion
Sponsors
Alector Inc.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmation of C9orf72 mutation * Diagnosis of ALS by revised El Escorial criteria * Time since onset of muscle weakness due to ALS ≤36 months at the time of the Screening Visit * Slow Vital Capacity (VC) ≥50% of predicted capacity at the time of the Screening Visit * If taking riluzole, must be on a stable dose of riluzole for at least 30 days prior to the Screening Visit. Riluzole naive participants are allowed. * If taking edaravone, must have completed at least one cycle of edaravone prior to the Screening Visit and plan to continue edaravone during the study. Edaravone naive participants are allowed. * Females must not be pregnant, breastfeeding or planning to conceive within the study period. Males must agree to use acceptable contraception * Capable of providing informed consent at the Screening visit and complying with study procedures throughout the study
Exclusion criteria
* Clinically significant, unstable, medical condition (other than ALS) * Clinically significant heart disease, liver disease or kidney disease * Cognitive impairment or dementia * Current uncontrolled hypertension * History of unresolved cancer * Any experimental gene therapy * Any experimental vaccine (any vaccine against COVID-19 either approved or administered under an Emergency Use Authorization is allowed)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Safety and Tolerability of AL001 Measured by Number of Subjects With Adverse Events | 24 weeks | Count of participants with adverse events during the study treatment period |
| Immunogenicity of AL001 | Week 24 | Count of participants positive for Anti-drug Antibodies (ADAs) to AL001 at week 24 |
| Pharmacokinetics (PK) of AL001 in Serum | Week 24 | Concentration of AL001 in Serum at week 24 |
| Pharmacokinetics (PK) of AL001 in CSF | Week 24 | Concentration of AL001 in Cerebrospinal fluid (CSF) at week 24 |
| Change From Baseline in Plasma Progranulin | 24 weeks | Evaluate the change from baseline to week 24 in plasma progranulin levels |
| Change From Baseline in CSF Progranulin | 24 weeks | Evaluate the change from baseline to week 24 in Cerebrospinal fluid (CSF) progranulin levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Neurofilament Light Chain | 24 weeks | Evaluate the change from baseline to week 24 in plasma neurofilament light chain levels |
| Change From Baseline in CSF Neurofilament Light Chain | 24 weeks | Evaluate change from baseline to week 24 in Cerebrospinal fluid (CSF) neurofilament light chain levels |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AL001 AL001 every 4 weeks
AL001: Administered via intravenous (IV) infusion | 3 |
| Placebo Placebo every 4 weeks
Placebo: Administered via intravenous (IV) infusion | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | AL001 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 2 / 3 | 2 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
Change From Baseline in CSF Progranulin
Evaluate the change from baseline to week 24 in Cerebrospinal fluid (CSF) progranulin levels
Time frame: 24 weeks
Population: Due to early termination of the study and insufficient sample size, no population-level analysis (within-group and between-group) was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AL001 | Change From Baseline in CSF Progranulin | 2.865 ng/mL | Standard Deviation 1.0677 |
| Placebo | Change From Baseline in CSF Progranulin | -0.385 ng/mL | Standard Deviation 0.3323 |
Primary
Change From Baseline in Plasma Progranulin
Evaluate the change from baseline to week 24 in plasma progranulin levels
Time frame: 24 weeks
Population: Due to early termination of the study and insufficient sample size, no population-level analysis (within-group and between-group) was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AL001 | Change From Baseline in Plasma Progranulin | 175 ng/mL | Standard Deviation 2.8284 |
| Placebo | Change From Baseline in Plasma Progranulin | -24.4 ng/mL | Standard Deviation 9.3338 |
Primary
Evaluation of Safety and Tolerability of AL001 Measured by Number of Subjects With Adverse Events
Count of participants with adverse events during the study treatment period
Time frame: 24 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AL001 | Evaluation of Safety and Tolerability of AL001 Measured by Number of Subjects With Adverse Events | 2 Participants |
| Placebo | Evaluation of Safety and Tolerability of AL001 Measured by Number of Subjects With Adverse Events | 2 Participants |
Primary
Immunogenicity of AL001
Count of participants positive for Anti-drug Antibodies (ADAs) to AL001 at week 24
Time frame: Week 24
Population: Due to early termination of the study and insufficient sample size, no population-level analysis (within-group and between-group) was performed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AL001 | Immunogenicity of AL001 | 1 Participants |
| Placebo | Immunogenicity of AL001 | 0 Participants |
Primary
Pharmacokinetics (PK) of AL001 in CSF
Concentration of AL001 in Cerebrospinal fluid (CSF) at week 24
Time frame: Week 24
Population: Due to early termination of the study and insufficient sample size, no population-level analysis (within-group and between-group) was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AL001 | Pharmacokinetics (PK) of AL001 in CSF | 547.5 ng/mL | Standard Deviation 395.2727 |
Primary
Pharmacokinetics (PK) of AL001 in Serum
Concentration of AL001 in Serum at week 24
Time frame: Week 24
Population: Due to early termination of the study and insufficient sample size, no population-level analysis (within-group and between-group) was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AL001 | Pharmacokinetics (PK) of AL001 in Serum | 705792.5 ng/mL | Standard Deviation 87387.7916 |
Secondary
Change From Baseline in CSF Neurofilament Light Chain
Evaluate change from baseline to week 24 in Cerebrospinal fluid (CSF) neurofilament light chain levels
Time frame: 24 weeks
Population: Due to early termination of the study and insufficient sample size, no population-level analysis (within-group and between-group) was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AL001 | Change From Baseline in CSF Neurofilament Light Chain | 995.5 pg/mL | Standard Deviation 95.4594 |
| Placebo | Change From Baseline in CSF Neurofilament Light Chain | -1250.5 pg/mL | Standard Deviation 825.1936 |
Secondary
Change From Baseline in Plasma Neurofilament Light Chain
Evaluate the change from baseline to week 24 in plasma neurofilament light chain levels
Time frame: 24 weeks
Population: Due to early termination of the study and insufficient sample size, no population-level analysis (within-group and between-group) was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AL001 | Change From Baseline in Plasma Neurofilament Light Chain | -0.35 pg/mL | Standard Deviation 3.3234 |
| Placebo | Change From Baseline in Plasma Neurofilament Light Chain | 1.9 pg/mL | Standard Deviation 2.8284 |