Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Placebo-Controlled, Double-Blind, Regimen Specific Appendix, Lou Gehrig's Disease, Trehalose, Seelos Therapeutics
Brief summary
The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. Regimen E will evaluate the safety and efficacy of a single study drug, SLS-005 (Trehalose injection, 90.5 mg/mL for intravenous infusion) in participants with ALS.
Detailed description
The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. This trial is designed as a perpetual platform trial. This means that there is a single Master Protocol dictating the conduct of the trial. The HEALEY ALS Platform Trial Master Protocol is registered as NCT04297683. Once a participant enrolls into the Master Protocol and meets all eligibility criteria, the participant will be eligible to be randomized into any currently enrolling regimen. All participants will have an equal chance of being randomized to any currently enrolling regimen. If a participant is randomized to Regimen E SLS-005 - Trehalose, the participant will complete a screening visit to assess additional Regimen E eligibility criteria. Once Regimen E eligibility criteria are confirmed, participants will complete a baseline assessment and be randomized in a 3:1 ratio to either active SLS-005 or matching placebo. Regimen E will enroll by invitation, as participants may not choose to enroll in Regimen E. Participants must first enroll into the Master Protocol and be eligible to participate in the Master Protocol before being able to be randomly assigned to Regimen E. For a list of enrolling sites, please see the HEALEY ALS Platform Trial Master Protocol under NCT04297683.
Interventions
DRUGSLS-005
Administration: Infusion Dose: 0.75 g/kg weekly
DRUGMatching Placebo
Administration: Infusion Dose: equivalent weight-based volume as described for trehalose
Sponsors
Seelos Therapeutics, Inc.
Merit E. Cudkowicz, MD
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
* No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT NCT04297683).
Exclusion criteria
* The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Progression as Assessed by the ALSFRS-R Slope | 24 Weeks | Change in disease severity over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). 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. |
| Mortality Event Rate | Baseline to 24 Weeks | Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row. The rate of mortality was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory Function | Baseline to 24 Weeks | Change in respiratory function over time as measured by Slow Vital Capacity (SVC). |
| Muscle Strength | Baseline to 24 Weeks | Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD). |
| Number of Participants That Experienced Death or Death Equivalent | Baseline to 24 Weeks | The number of participants who died or met the criterion for a death equivalent from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline). The death equivalent criterion is the use of permanent assisted ventilation (PAV) for more than 22 hours per day for more than 7 days in a row. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SLS-005 SLS-005 is administered via infusion once weekly for 24 weeks.
SLS-005: Administration: Infusion Dose: 0.75 g/kg weekly | 120 |
| Matching Placebo Matching placebo is administered via infusion once weekly for 24 weeks.
Matching Placebo: Administration: Infusion Dose: equivalent weight-based volume as described for trehalose | 41 |
| Total | 161 |
Baseline characteristics
| Characteristic | Matching Placebo | SLS-005 | Total |
|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 10.19 | 59.3 years STANDARD_DEVIATION 10.73 | 59.8 years STANDARD_DEVIATION 10.6 |
| ALS Diagnosis from R El Escorial Criteria Clinically Definite ALS | 17 Participants | 44 Participants | 61 Participants |
| ALS Diagnosis from R El Escorial Criteria Clinically Possible ALS | 3 Participants | 8 Participants | 11 Participants |
| ALS Diagnosis from R El Escorial Criteria Clinically Probable ALS | 13 Participants | 40 Participants | 53 Participants |
| ALS Diagnosis from R El Escorial Criteria Clinically Probable ALS - Laboratory Supported | 8 Participants | 28 Participants | 36 Participants |
| ALSFRS-R Total Score | 35.0 Points STANDARD_DEVIATION 6.71 | 35.8 Points STANDARD_DEVIATION 6.43 | 35.6 Points STANDARD_DEVIATION 6.49 |
| ALS Onset Location Bulbar | 11 Participants | 25 Participants | 36 Participants |
| ALS Onset Location Limb | 27 Participants | 93 Participants | 120 Participants |
| ALS Onset Location Multiple | 1 Participants | 2 Participants | 3 Participants |
| ALS Onset Location Respiratory | 2 Participants | 0 Participants | 2 Participants |
| Baseline Decline in ALSFRS-R | 0.76 points per month STANDARD_DEVIATION 0.504 | 0.76 points per month STANDARD_DEVIATION 0.608 | 0.76 points per month STANDARD_DEVIATION 0.582 |
| Baseline Edaravone Use No | 28 Participants | 84 Participants | 112 Participants |
| Baseline Edaravone Use Yes | 13 Participants | 36 Participants | 49 Participants |
| Baseline Riluzole Use No | 11 Participants | 33 Participants | 44 Participants |
| Baseline Riluzole Use Yes | 30 Participants | 87 Participants | 117 Participants |
| Body Mass Index | 26.8 kg/cm^2 STANDARD_DEVIATION 5.15 | 26.7 kg/cm^2 STANDARD_DEVIATION 6.47 | 26.7 kg/cm^2 STANDARD_DEVIATION 6.14 |
| Delay in ALS Symptom Onset and Diagnosis | 10.1 Months STANDARD_DEVIATION 4.82 | 10.7 Months STANDARD_DEVIATION 6.86 | 10.5 Months STANDARD_DEVIATION 6.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 115 Participants | 155 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| King Stage 1 Region with Neuromuscular Dysfunction | 8 Participants | 20 Participants | 28 Participants |
| King Stage 2 Region with Neuromuscular Dysfunction | 13 Participants | 38 Participants | 51 Participants |
| King Stage 3 Region with Neuromuscular Dysfunction | 5 Participants | 36 Participants | 41 Participants |
| King Stage 4a/b Nutritional/Respiratory Failure | 15 Participants | 26 Participants | 41 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 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 | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 39 Participants | 109 Participants | 148 Participants |
| Serum Creatinine Concentration | 0.7 mg/dL STANDARD_DEVIATION 0.16 | 0.7 mg/dL STANDARD_DEVIATION 0.19 | 0.7 mg/dL STANDARD_DEVIATION 0.18 |
| Serum NfL Concentration | 76.5 ng/L STANDARD_DEVIATION 38.45 | 76.9 ng/L STANDARD_DEVIATION 51.08 | 76.8 ng/L STANDARD_DEVIATION 48.09 |
| Sex: Female, Male Female | 24 Participants | 55 Participants | 79 Participants |
| Sex: Female, Male Male | 17 Participants | 65 Participants | 82 Participants |
| SVC | 77.9 percent predicted STANDARD_DEVIATION 16.54 | 74.5 percent predicted STANDARD_DEVIATION 18.81 | 75.4 percent predicted STANDARD_DEVIATION 18.26 |
| Time Since Symptom Onset at Baseline | 19.9 Months STANDARD_DEVIATION 8.2 | 19.6 Months STANDARD_DEVIATION 8.61 | 19.7 Months STANDARD_DEVIATION 8.48 |
| Weight | 76.8 kg STANDARD_DEVIATION 17.65 | 79.3 kg STANDARD_DEVIATION 21.44 | 78.6 kg STANDARD_DEVIATION 20.52 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 120 | 0 / 41 |
| other Total, other adverse events | 107 / 120 | 33 / 41 |
| serious Total, serious adverse events | 19 / 120 | 3 / 41 |
Outcome results
Primary
Disease Progression as Assessed by the ALSFRS-R Slope
Change in disease severity over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). 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.
Time frame: 24 Weeks
Population: Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A (NCT04436497), Regimen B (NCT04436510), Regimen C (NCT04414345) and Regimen D (NCT04615923) contributed placebo participants into the shared placebo cohort used for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SLS-005 | Disease Progression as Assessed by the ALSFRS-R Slope | -0.91 points per month | Standard Deviation 0.09 |
| Matching Placebo | Disease Progression as Assessed by the ALSFRS-R Slope | -1.06 points per month | Standard Deviation 0.091 |
95% CI: [0.665, 1.102]Bayesian shared-parameter model
Primary
Mortality Event Rate
Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row. The rate of mortality was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times.
Time frame: Baseline to 24 Weeks
Population: Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A (NCT04436497), Regimen B (NCT04436510), Regimen C (NCT04414345) and Regimen D (NCT04615923) contributed placebo participants into the shared placebo cohort used for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SLS-005 | Mortality Event Rate | 0.010 events per month | Standard Deviation 0.0025 |
| Matching Placebo | Mortality Event Rate | 0.012 events per month | Standard Deviation 0.0027 |
Secondary
Muscle Strength
Change in muscle strength over time as measured isometrically using hand-held dynamometry (HHD).
Time frame: Baseline to 24 Weeks
Population: Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A (NCT04436497), Regimen B (NCT04436510), Regimen C (NCT04414345) and Regimen D (NCT04615923) contributed placebo participants into the shared placebo cohort used for analysis. Two placebo participants from FAS were not analyzed due to missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLS-005 | Muscle Strength | -26.19 percent change | Standard Error 2.568 |
| Matching Placebo | Muscle Strength | -27.11 percent change | Standard Error 1.876 |
p-value: 0.773795% CI: [-5.37, 7.21]Mixed Models Analysis
Secondary
Number of Participants That Experienced Death or Death Equivalent
The number of participants who died or met the criterion for a death equivalent from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline). The death equivalent criterion is the use of permanent assisted ventilation (PAV) for more than 22 hours per day for more than 7 days in a row.
Time frame: Baseline to 24 Weeks
Population: Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A (NCT04436497), Regimen B (NCT04436510), Regimen C (NCT04414345) and Regimen D (NCT04615923) contributed placebo participants into the shared placebo cohort used for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SLS-005 | Number of Participants That Experienced Death or Death Equivalent | 10 Participants |
| Matching Placebo | Number of Participants That Experienced Death or Death Equivalent | 10 Participants |
p-value: 0.2137Log Rank
Secondary
Respiratory Function
Change in respiratory function over time as measured by Slow Vital Capacity (SVC).
Time frame: Baseline to 24 Weeks
Population: Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A (NCT04436497), Regimen B (NCT04436510), Regimen C (NCT04414345) and Regimen D (NCT04615923) contributed placebo participants into the shared placebo cohort used for analysis.One SLS-005 participant and 4 placebo participants from FAS were not analyzed due to missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLS-005 | Respiratory Function | -11.40 percent change | Standard Error 1.431 |
| Matching Placebo | Respiratory Function | -10.85 percent change | Standard Error 1.089 |
p-value: 0.760795% CI: [-4.06, 2.97]Mixed Models Analysis