Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS
Brief summary
About 213 people with ALS will participate in this study. There will be locations in North and South America. During the first part, participants will be randomly assigned to a group (like by flipping a coin). Out of every 3: * 2 will get the study drug * 1 will get a look-alike with no drug in it (placebo) During the second part, everyone will get the study drug. Participation will help doctors find out if Acthar can help or slow down the symptoms of ALS better than placebo.
Detailed description
This is a multicenter, multiple dose study to examine the effect of Acthar on functional decline in adult participants with ALS. Approximately 213 participants will be enrolled. Following a screening period of up to 28 days, participants with ALS and symptom onset (defined as first muscle weakness or dysarthria) ≤ 2 years prior to the Screening Visit will be randomized on a 2:1 basis to receive subcutaneous (SC) Acthar 0.2 mL (16 Units \[U\]) daily (QD) or SC matching placebo 0.2 mL QD for 36 weeks, followed by a 3-week taper. Participants who complete the 36 week double-blind treatment period are eligible to enter an Open Label Extension phase in which all participants will receive Acthar 0.2 mL (16 U) daily.
Interventions
DRUGActhar
Repository corticotropin for subcutaneous injection
DRUGPlacebo
Matching placebo for subcutaneous injection
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The Treatment Period is defined as Randomized (2:1, Arm A: Arm B), Double-blind (with care provider and outcomes assessor also blinded). The Extension Period has no masking, because all who participate receive open label study drug.
Intervention model description
Participants will be assigned to treatment group randomly (like flipping a coin). They will have a 2 out of 3 chance of receiving the study drug, and a 1 out of 3 chance of receiving placebo during the treatment period. All participants who continue into the extension period receive Acthar.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Is 18-75 years of age at Screening 2. Has ALS symptom onset within 2 years prior to Screening 3. Has forced vital capacity (FVC) no higher than 60% at screening 4. If taking riluzole, is on a stable dose for 4 weeks before Screening
Exclusion criteria
1. Has tracheostomy, diaphragm pacing, or an ongoing need for assisted ventilation of any type 2. Has used any medication within a time period not allowed per protocol 3. Has history of Type 1 or Type 2 diabetes mellitus, or any clinically significant infection 4. Used edaravone less than 1 week before Screening 5. Received any stem cell replacement therapy 6. Used steroids within a time period not allowed per protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Period: Scores on a Scale for Telephone-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Baseline, Week 36 | The ALSFRS-R is a validated questionnaire-based scale used extensively as a primary outcome measure in ALS clinical trials and is considered a predictor of survival. ALSFRS-R is a 12-item scale that measures 4 domains relevant for ALS (gross motor, fine motor, bulbar and respiratory) A trained, independent rater calls each participant (or the caregiver) to administer the questionnaire. The 12 functions are rated on a scale from 0 to 4, with a highest possible (summed) score of 48. Higher scores represent better function. |
| Number of Participants Experiencing an Adverse Event During the Treatment Period | by the end of the treatment period (within 36 Weeks) | Serious adverse events, non-serious treatment-emergent adverse events, and all-cause mortality are collected until the participant no longer participates in the study Clinically significant changes in safety measures are recorded as adverse events. |
| Number of Participants Experiencing an Adverse Event by the End of the Trial in the OLE Period | by the time of database lock (within 84 weeks) | Serious adverse events, non-serious treatment-emergent adverse events, and all-cause mortality are collected until the participant no longer participates in the study (estimated about 1 year for participants leaving after the treatment period, and two years for participants who participate also in the open label extension). Clinically significant changes in safety measures are recorded as adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Period: Spirometry (%) | Baseline, Week 36 | Spirometry (meaning the measuring of breath) is the most common of the lung function tests. It measures how much air can be inhaled \[Forced Vital Capacity (FVC)\] and exhaled \[(Forced Expiratory Volume in one second (FEV1)\]. |
| Treatment Period: Scores on a Scale for Investigator-administered ALSFRS-R | Baseline, Week 36 | The ALSFRS-R is a 12-item scale evaluating 4 domains relevant to ALS (gross motor, fine motor, bulbar and respiratory). The trained investigator (or designee) administers the ALSFRS-R questionnaire in person with the participant (or caregiver). The 12 functions are rated on a scale from 0 to 4, with a highest possible (summed) score of 48. Higher scores represent better function. |
| Extension Period: Scores on a Scale for Investigator-administered ALSFRS-R | Baseline, Week 84 | The ALSFRS-R is a 12-item scale evaluating 4 domains relevant to ALS (gross motor, fine motor, bulbar and respiratory). The trained investigator (or designee) administers the ALSFRS-R questionnaire in person with the participant (or caregiver). The 12 functions are rated on a scale from 0 to 4, with a highest possible score of 48. Higher scores represent better function. |
Countries
Argentina, Canada, Chile, Colombia, Mexico, Peru, United States
Participant flow
Pre-assignment details
Of 207 potential participants screened, 143 were randomized to begin treatment
Participants by arm
| Arm | Count |
|---|---|
| Arm A: RTP Acthar Gel Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks.
Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39. | 95 |
| Arm B: RTP Placebo Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks.
Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39. | 47 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Open Label Extension Period (OLE) | Adverse Event | 0 | 0 | 0 | 1 |
| Open Label Extension Period (OLE) | Death | 0 | 0 | 0 | 1 |
| Open Label Extension Period (OLE) | Disease progression | 0 | 0 | 3 | 1 |
| Open Label Extension Period (OLE) | Subject Discontinued for Non-efficacy | 0 | 0 | 1 | 0 |
| Open Label Extension Period (OLE) | Trial Terminated by Sponsor | 0 | 0 | 12 | 3 |
| Open Label Extension Period (OLE) | Withdrawal by Subject | 0 | 0 | 5 | 0 |
| Randomized Treatment Period (RTP) | Adverse Event | 1 | 3 | 0 | 0 |
| Randomized Treatment Period (RTP) | Death | 2 | 2 | 0 | 0 |
| Randomized Treatment Period (RTP) | Discontinued by Physician | 1 | 0 | 0 | 0 |
| Randomized Treatment Period (RTP) | Disease progression | 1 | 2 | 0 | 0 |
| Randomized Treatment Period (RTP) | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Randomized Treatment Period (RTP) | Subject Decision based on Compensation | 0 | 1 | 0 | 0 |
| Randomized Treatment Period (RTP) | Trial Terminated by Sponsor | 55 | 29 | 0 | 0 |
| Randomized Treatment Period (RTP) | Withdrawal by Subject | 6 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm B: RTP Placebo | Arm A: RTP Acthar Gel | Total |
|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 10.68 | 55.9 years STANDARD_DEVIATION 10.8 | 56.0 years STANDARD_DEVIATION 10.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 38 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 57 Participants | 85 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 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 | 11 Participants | 15 Participants | 26 Participants |
| Race (NIH/OMB) White | 33 Participants | 72 Participants | 105 Participants |
| Sex: Female, Male Female | 21 Participants | 35 Participants | 56 Participants |
| Sex: Female, Male Male | 26 Participants | 60 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 95 | 3 / 47 | 1 / 25 | 2 / 8 |
| other Total, other adverse events | 71 / 95 | 34 / 47 | 18 / 25 | 7 / 8 |
| serious Total, serious adverse events | 13 / 95 | 6 / 47 | 4 / 25 | 2 / 8 |
Outcome results
Primary
Number of Participants Experiencing an Adverse Event by the End of the Trial in the OLE Period
Serious adverse events, non-serious treatment-emergent adverse events, and all-cause mortality are collected until the participant no longer participates in the study (estimated about 1 year for participants leaving after the treatment period, and two years for participants who participate also in the open label extension). Clinically significant changes in safety measures are recorded as adverse events.
Time frame: by the time of database lock (within 84 weeks)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: RTP Acthar Gel | Number of Participants Experiencing an Adverse Event by the End of the Trial in the OLE Period | Serious Treatment Emergent Adverse Events | 4 Participants |
| Arm A: RTP Acthar Gel | Number of Participants Experiencing an Adverse Event by the End of the Trial in the OLE Period | Non-serious Treatment-Emergent Adverse Events | 20 Participants |
| Arm B: RTP Placebo | Number of Participants Experiencing an Adverse Event by the End of the Trial in the OLE Period | Serious Treatment Emergent Adverse Events | 2 Participants |
| Arm B: RTP Placebo | Number of Participants Experiencing an Adverse Event by the End of the Trial in the OLE Period | Non-serious Treatment-Emergent Adverse Events | 7 Participants |
Primary
Number of Participants Experiencing an Adverse Event During the Treatment Period
Serious adverse events, non-serious treatment-emergent adverse events, and all-cause mortality are collected until the participant no longer participates in the study Clinically significant changes in safety measures are recorded as adverse events.
Time frame: by the end of the treatment period (within 36 Weeks)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: RTP Acthar Gel | Number of Participants Experiencing an Adverse Event During the Treatment Period | Serious Treatment Emergent Adverse Events | 13 Participants |
| Arm A: RTP Acthar Gel | Number of Participants Experiencing an Adverse Event During the Treatment Period | Non-serious Treatment-Emergent Adverse Events | 74 Participants |
| Arm A: RTP Acthar Gel | Number of Participants Experiencing an Adverse Event During the Treatment Period | Death | 2 Participants |
| Arm B: RTP Placebo | Number of Participants Experiencing an Adverse Event During the Treatment Period | Serious Treatment Emergent Adverse Events | 6 Participants |
| Arm B: RTP Placebo | Number of Participants Experiencing an Adverse Event During the Treatment Period | Non-serious Treatment-Emergent Adverse Events | 40 Participants |
| Arm B: RTP Placebo | Number of Participants Experiencing an Adverse Event During the Treatment Period | Death | 3 Participants |
Primary
Treatment Period: Scores on a Scale for Telephone-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
The ALSFRS-R is a validated questionnaire-based scale used extensively as a primary outcome measure in ALS clinical trials and is considered a predictor of survival. ALSFRS-R is a 12-item scale that measures 4 domains relevant for ALS (gross motor, fine motor, bulbar and respiratory) A trained, independent rater calls each participant (or the caregiver) to administer the questionnaire. The 12 functions are rated on a scale from 0 to 4, with a highest possible (summed) score of 48. Higher scores represent better function.
Time frame: Baseline, Week 36
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: RTP Acthar Gel | Treatment Period: Scores on a Scale for Telephone-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Baseline | 34.7 score on a scale | Standard Deviation 6.01 |
| Arm A: RTP Acthar Gel | Treatment Period: Scores on a Scale for Telephone-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Week 36 | 26.4 score on a scale | Standard Deviation 9.34 |
| Arm B: RTP Placebo | Treatment Period: Scores on a Scale for Telephone-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Baseline | 34.3 score on a scale | Standard Deviation 5.84 |
| Arm B: RTP Placebo | Treatment Period: Scores on a Scale for Telephone-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Week 36 | 30.8 score on a scale | Standard Deviation 7.55 |
Secondary
Extension Period: Scores on a Scale for Investigator-administered ALSFRS-R
The ALSFRS-R is a 12-item scale evaluating 4 domains relevant to ALS (gross motor, fine motor, bulbar and respiratory). The trained investigator (or designee) administers the ALSFRS-R questionnaire in person with the participant (or caregiver). The 12 functions are rated on a scale from 0 to 4, with a highest possible score of 48. Higher scores represent better function.
Time frame: Baseline, Week 84
Population: OLE population with scores at the given week; baseline is defined as the value at randomization (week 0)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: RTP Acthar Gel | Extension Period: Scores on a Scale for Investigator-administered ALSFRS-R | Baseline | 36.8 units on a scale | Standard Deviation 5.33 |
| Arm A: RTP Acthar Gel | Extension Period: Scores on a Scale for Investigator-administered ALSFRS-R | Week 84 | 27.4 units on a scale | Standard Deviation 5.41 |
| Arm B: RTP Placebo | Extension Period: Scores on a Scale for Investigator-administered ALSFRS-R | Baseline | 39.6 units on a scale | Standard Deviation 1.81 |
| Arm B: RTP Placebo | Extension Period: Scores on a Scale for Investigator-administered ALSFRS-R | Week 84 | 21.5 units on a scale | Standard Deviation 4.95 |
Secondary
Treatment Period: Scores on a Scale for Investigator-administered ALSFRS-R
The ALSFRS-R is a 12-item scale evaluating 4 domains relevant to ALS (gross motor, fine motor, bulbar and respiratory). The trained investigator (or designee) administers the ALSFRS-R questionnaire in person with the participant (or caregiver). The 12 functions are rated on a scale from 0 to 4, with a highest possible (summed) score of 48. Higher scores represent better function.
Time frame: Baseline, Week 36
Population: Safety Population, with an actual score at the given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: RTP Acthar Gel | Treatment Period: Scores on a Scale for Investigator-administered ALSFRS-R | Baseline | 35.8 score on a scale | Standard Deviation 6.05 |
| Arm A: RTP Acthar Gel | Treatment Period: Scores on a Scale for Investigator-administered ALSFRS-R | Week 36 | 28.0 score on a scale | Standard Deviation 9.5 |
| Arm B: RTP Placebo | Treatment Period: Scores on a Scale for Investigator-administered ALSFRS-R | Baseline | 35.4 score on a scale | Standard Deviation 6.23 |
| Arm B: RTP Placebo | Treatment Period: Scores on a Scale for Investigator-administered ALSFRS-R | Week 36 | 30.9 score on a scale | Standard Deviation 7.18 |
Secondary
Treatment Period: Spirometry (%)
Spirometry (meaning the measuring of breath) is the most common of the lung function tests. It measures how much air can be inhaled \[Forced Vital Capacity (FVC)\] and exhaled \[(Forced Expiratory Volume in one second (FEV1)\].
Time frame: Baseline, Week 36
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: RTP Acthar Gel | Treatment Period: Spirometry (%) | FVC at Baseline | 85.0 liters | Standard Deviation 18.31 |
| Arm A: RTP Acthar Gel | Treatment Period: Spirometry (%) | FEV1 at Baseline | 79.3 liters | Standard Deviation 18.78 |
| Arm A: RTP Acthar Gel | Treatment Period: Spirometry (%) | FEV1 at Week 36 | 59.1 liters | Standard Deviation 27.37 |
| Arm A: RTP Acthar Gel | Treatment Period: Spirometry (%) | FVC at Week 36 | 61.4 liters | Standard Deviation 27.37 |
| Arm B: RTP Placebo | Treatment Period: Spirometry (%) | FEV1 at Week 36 | 54.3 liters | Standard Deviation 26.79 |
| Arm B: RTP Placebo | Treatment Period: Spirometry (%) | FVC at Baseline | 82.1 liters | Standard Deviation 17.6 |
| Arm B: RTP Placebo | Treatment Period: Spirometry (%) | FVC at Week 36 | 63.8 liters | Standard Deviation 26.05 |
| Arm B: RTP Placebo | Treatment Period: Spirometry (%) | FEV1 at Baseline | 77.8 liters | Standard Deviation 18.52 |