Study of Acthar® Gel (Acthar) for Amyotrophic Lateral Sclerosis (ALS)

Study Overview
=================
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.

Official Title
-----------------
A Multicenter, Double Blind, Placebo Controlled Study to Assess the Efficacy and Safety of H.P. Acthar® Gel in the Treatment of Subjects With Amyotrophic Lateral Sclerosis

Conditions
-----------------
Amyotrophic Lateral Sclerosis

Intervention / Treatment
-----------------
* Drug: Acthar
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is 18-75 years of age at Screening Has ALS symptom onset within 2 years prior to Screening Has forced vital capacity (FVC) no higher than 60% at screening If taking riluzole, is on a stable dose for 4 weeks before Screening Exclusion Criteria: Has tracheostomy, diaphragm pacing, or an ongoing need for assisted ventilation of any type Has used any medication within a time period not allowed per protocol Has history of Type 1 or Type 2 diabetes mellitus, or any clinically significant infection Used edaravone less than 1 week before Screening Received any stem cell replacement therapy Used steroids within a time period not allowed per protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Treatment Period Acthar<br>Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar), 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. | Drug: Acthar<br>* Repository corticotropin for subcutaneous injection<br>* Other names: Generic name: repository corticotropin injection;|
| Placebo Comparator: Arm B: Treatment Period Placebo<br>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. | Drug: Placebo<br>* Matching placebo for subcutaneous injection<br>* Other names: Reference Product;|
| Experimental: Arm C: Extension Period Acthar-Acthar<br>Participants who receive Acthar during the treatment period and continue into the extension period do not go through the treatment-period tapering, but receive one 0.2 mL SC injection of Acthar, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months. | Drug: Acthar<br>* Repository corticotropin for subcutaneous injection<br>* Other names: Generic name: repository corticotropin injection;|
| Experimental: Arm D: Extension Period Placebo-Acthar<br>Participants who receive Placebo during the treatment period and continue into the extension period do not go through the treatment-period simulated tapering, but receive one 0.2 mL SC injection of Acthar, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months. | Drug: Acthar<br>* Repository corticotropin for subcutaneous injection<br>* Other names: Generic name: repository corticotropin injection;Drug: Placebo<br>* Matching placebo for subcutaneous injection<br>* Other names: Reference Product;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 36 | 
| 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. | by the end of the treatment period (within 36 Weeks) | 
| 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. | by the time of database lock (within 84 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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)]. | Baseline, Week 36 | 
| 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. | Baseline, Week 36 | 
| 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. | Baseline, Week 84 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ALS