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

• Sponsor: Mallinckrodt (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03068754
• Collaborator: (none)
• Enrollment: 143
• Locations: 69
• Arms: 4
• Actual Duration (Months): 29.1
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: Acthar; Drug: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 143 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.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 (Participant, 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.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jun 22, 2017
• Actual Primary Completion Date: Nov 25, 2019
• Actual Study Completion Date: Nov 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Treatment Period Acthar 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; Repository corticotropin for subcutaneous injection; Other Names: Trade name: Acthar® Gel Generic name: repository corticotropin injection
Placebo Comparator: Arm B: Treatment Period 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.	Drug: Placebo; Matching placebo for subcutaneous injection; Other Names: Matching Placebo Reference Product
Experimental: Arm C: Extension Period Acthar-Acthar 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; Repository corticotropin for subcutaneous injection; Other Names: Trade name: Acthar® Gel Generic name: repository corticotropin injection
Experimental: Arm D: Extension Period Placebo-Acthar 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; Repository corticotropin for subcutaneous injection; Other Names: Trade name: Acthar® Gel Generic name: repository corticotropin injection ; Drug: Placebo; Matching placebo for subcutaneous injection; Other Names: Matching Placebo Reference Product

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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)].

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neuromuscular Research Center	Phoenix	Arizona	United States	85028
2	Mayo Clinic - Arizona	Scottsdale	Arizona	United States	85259
3	University of California San Diego	La Jolla	California	United States	92037
4	Loma Linda University Health System, Department of Neurology	Loma Linda	California	United States	92354
5	Keck School of Medicine, University of Southern California	Los Angeles	California	United States	90033
6	University of California Los Angeles	Los Angeles	California	United States	90095
7	University of California Irvine Medical Center	Orange	California	United States	92868
8	California Pacific Medical Center	San Francisco	California	United States	94115
9	University of California San Francisco	San Francisco	California	United States	94143
10	Colorado Springs Neurological Associates	Colorado Springs	Colorado	United States	80907
11	Georgetown University	Washington	District of Columbia	United States	20007
12	George Washington University	Washington	District of Columbia	United States	20037
13	University of Florida - McKnight Brain Institute	Gainesville	Florida	United States	32611
14	University of South Florida	Tampa	Florida	United States	33612
15	Emory University	Atlanta	Georgia	United States	30322
16	Augusta University	Augusta	Georgia	United States	30912
17	Indiana University-Neuroscience Center of Excellence/Goodman Hall	Indianapolis	Indiana	United States	46202
18	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
19	University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536
20	John Hopkins Outpatient Center	Baltimore	Maryland	United States	21287
21	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
22	Mercy Health- Saint Mary's	Grand Rapids	Michigan	United States	49503
23	Neurology Associates	Lincoln	Nebraska	United States	68510
24	University of Nebraska Medical Center - Physicians Clinical Neurosciences Center	Omaha	Nebraska	United States	68198
25	Las Vegas Clinic	Las Vegas	Nevada	United States	89145
26	Jersey Shore University Medical Center	Neptune	New Jersey	United States	07753
27	Columbia Presbyterian Hospital	New York	New York	United States	10032
28	Providence ALS Center	Portland	Oregon	United States	97213
29	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
30	Temple University School of Medicine	Philadelphia	Pennsylvania	United States	19140
31	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
32	Wesley Neurology Clinic	Cordova	Tennessee	United States	38018
33	Austin Neuromuscular Center	Austin	Texas	United States	78756
34	Texas Neurology, P.A.	Dallas	Texas	United States	75214
35	The Methodist Hospital	Houston	Texas	United States	77030
36	University of Vermont Medical Center	Colchester	Vermont	United States	05401
37	VCU Medical Center	Richmond	Virginia	United States	23298
38	Swedish Neuroscience Institute	Seattle	Washington	United States	98122
39	Medical College of Wisconsin/Froedtert Hospital	Milwaukee	Wisconsin	United States	53226
40	IADIN	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1015ABR
41	STAT Research	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1023AAB
42	DIABAID	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1061ABD
43	INEBA	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1192AAW
44	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1199ABB
45	Hospital Español	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1209AAB
46	Hospital Británico de Buenos Aires	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1280AEB
47	ILAIM	Ciudad de Córdoba	Córdoba	Argentina	X5000BNB
48	Fundación Scherbovsky	Ciudad de Mendoza	Mendoza	Argentina	CP 5500
49	Instituto de Neurología y Neurorrehabilitación del Litoral (INNeL )	Ciudad De Santa Fe	Santa Fe	Argentina	S3000ASL
50	Edmonton Kaye Clinic	Edmonton	Alberta	Canada	T6G 1Z1
51	Recherche Sepmus inc	Greenfield Park	Quebec	Canada	J4V 2J2
52	Centre de recherché du Centre Hospitalier de l'Universite de Montreal (CRCHUM)	Montréal	Quebec	Canada	H2XOA9
53	Montreal Neurological Institute & Hospital	Montréal	Quebec	Canada	H3A 2B4
54	Centro de Trastornos del Movimiento (CETRAM)	Santiago	Región Metropolitana	Chile	8380815
55	Clinica Dávila	Santiago	Región Metropolitana	Chile	8431657
56	Biomedica Research Group AV Salvador 149, oficina 1101	Santiago		Chile	7500710
57	Centro de Investigaciones Clínicas SAS	Cali		Colombia	760036
58	Clinical Research Institute Saltillo S.A. de C.V.	Saltillo	Coahuila	Mexico	25020
59	Hospital Universitario "Dr. José Eleuterio González"	Monterrey	Nuevo Leon	Mexico	64460
60	SMIQ BRCR Global México	Querétaro City	Querétaro	Mexico	76090
61	Clinical Research Institute S.C.	San Lucas Tepetlacalco	Tlalnepantla De Baz	Mexico	54055
62	Centro Especializado en Investigación Clínica S.C.	Boca Del Río	Veracruz	Mexico	94290
63	Phylasis Clinicas Research	Mexico City		Mexico	54769
64	FAICIC Clinical Researc	Veracruz		Mexico	91900
65	Hospital Nivel IV Carlos Alberto Seguin Escobedo	Arequipa		Peru	04001
66	Hospital Nacional IV Alberto Sabogal Sologuren	Callao		Peru	07016
67	Hospital Almenara	Lima		Peru	15033
68	Instituto Neuro Cardiovascular de las Américas	Lima		Peru	15074
69	Hospital Nacional Cayetano Heredia	Lima		Peru	15102

Sponsors and Collaborators

• Mallinckrodt

Investigators

• Study Director: Clinical Team Leader, Mallinckrodt

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 11, 2017

More Information

Publications

None provided.

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT03068754
• Other Study ID Numbers: MNK14042068
• First Posted: Mar 3, 2017
• Last Update Posted: Oct 14, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mallinckrodt: ALS
• Additional relevant MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Adrenocorticotropic Hormone

Study Results

Participant Flow

Pre-assignment Detail	Of 207 potential participants screened, 143 were randomized to begin treatment

Arm/Group Title	Arm A: Randomized Treatment Period (RTP) Acthar Gel	Arm B: RTP Placebo	Arm C: Open Label Extension Period (OLE) Acthar Gel-Acthar Gel	Arm D: OLE Placebo-Acthar Gel
Arm/Group Description	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 had 3 weeks of tapering off the drug, ending their participation by Week 39.	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 had 3 weeks of simulated tapering, ending their participation by Week 39.	Participants who received Acthar Gel 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 Gel, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.	Participants who received 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.
Period Title: Randomized Treatment Period (RTP)
STARTED	95	48	0	0
Intention to Treat (ITT) Population	95	48	0	0
Safety Population	95	47	0	0
Modified ITT (mITT)	93	46	0	0
Completed Taper	58	28	0	0
Completed 36 Weeks of Treatment	28	9	0	0
Completed RTP	27	9	0	0
Enrolled in OLE Period	25	8	0	0
COMPLETED	28	9	0	0
NOT COMPLETED	67	39	0	0
Period Title: Randomized Treatment Period (RTP)
STARTED	0	0	25	8
Completed Taper	0	0	19	7
Completed OLE Period	0	0	3	2
Completed Treatment in OLE	0	0	4	2
COMPLETED	0	0	4	2
NOT COMPLETED	0	0	21	6

Baseline Characteristics

Arm/Group Title	Arm A: RTP Acthar Gel	Arm B: RTP Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	95	47	142
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.9 (10.80)	56.3 (10.68)	56.0 (10.72)
Sex: Female, Male (Count of Participants)
Female	35 36.8%	21 44.7%	56 39.4%
Male	60 63.2%	26 55.3%	86 60.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	38 40%	19 40.4%	57 40.1%
Not Hispanic or Latino	57 60%	28 59.6%	85 59.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	5 5.3%	2 4.3%	7 4.9%
Asian	1 1.1%	1 2.1%	2 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 2.1%	0 0%	2 1.4%
White	72 75.8%	33 70.2%	105 73.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	15 15.8%	11 23.4%	26 18.3%

Outcome Measures

1. Primary Outcome

Title	Treatment Period: Scores on a Scale for Telephone-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Arm A: RTP Acthar Gel	Arm B: RTP Placebo
Arm/Group Description	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.	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.
Measure Participants	95	47
Baseline	34.7 (6.01)	34.3 (5.84)
Week 36	26.4 (9.34)	30.8 (7.55)

2. Primary Outcome

Title	Number of Participants Experiencing an Adverse Event During the Treatment Period
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Arm A: RTP Acthar Gel	Arm B: RTP Placebo
Arm/Group Description	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.	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.
Measure Participants	95	47
Serious Treatment Emergent Adverse Events	13 13.7%	6 12.8%
Non-serious Treatment-Emergent Adverse Events	74 77.9%	40 85.1%
Death	2 2.1%	3 6.4%

3. Primary Outcome

Title	Number of Participants Experiencing an Adverse Event by the End of the Trial in the OLE Period
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Arm C: OLE Acthar Gel-Acthar Gel	Arm D: OLE Placebo-Acthar Gel
Arm/Group Description	Participants who receive Acthar Gel 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 Gel, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.	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.
Measure Participants	25	8
Serious Treatment Emergent Adverse Events	4 4.2%	2 4.3%
Non-serious Treatment-Emergent Adverse Events	20 21.1%	7 14.9%

4. Secondary Outcome

Title	Treatment Period: Spirometry (%)
Description	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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Arm A: RTP Acthar Gel	Arm B: RTP Placebo
Arm/Group Description	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.	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.
Measure Participants	95	47
FVC at Baseline	85.0 (18.31)	82.1 (17.60)
FVC at Week 36	61.4 (27.37)	63.8 (26.05)
FEV1 at Baseline	79.3 (18.78)	77.8 (18.52)
FEV1 at Week 36	59.1 (27.37)	54.3 (26.79)

5. Secondary Outcome

Title	Treatment Period: Scores on a Scale for Investigator-administered ALSFRS-R
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population, with an actual score at the given time point

Arm/Group Title	Arm A: RTP Acthar Gel	Arm B: RTP Placebo
Arm/Group Description	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.	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.
Measure Participants	95	47
Baseline	35.8 (6.05)	35.4 (6.23)
Week 36	28.0 (9.50)	30.9 (7.18)

6. Secondary Outcome

Title	Extension Period: Scores on a Scale for Investigator-administered ALSFRS-R
Description	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

Outcome Measure Data

Analysis Population Description

OLE population with scores at the given week; baseline is defined as the value at randomization (week 0)

Arm/Group Title	Arm C: OLE Acthar Gel-Acthar Gel	Arm D: OLE Placebo-Acthar Gel
Arm/Group Description	Participants who receive Acthar Gel 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 Gel, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.	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.
Measure Participants	25	7
Baseline	36.8 (5.33)	39.6 (1.81)
Week 84	27.4 (5.41)	21.5 (4.95)

Adverse Events

Time Frame	From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84)
Adverse Event Reporting Description	Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Arm/Group Title	Arm A: RTP Acthar Gel		Arm B: RTP Placebo		Arm C: OLE Acthar Gel-Acthar Gel		Arm D: OLE Placebo-Acthar Gel
Arm/Group Description	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.		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.		Participants who receive Acthar Gel 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 Gel, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.		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.
All Cause Mortality
	Arm A: RTP Acthar Gel		Arm B: RTP Placebo		Arm C: OLE Acthar Gel-Acthar Gel		Arm D: OLE Placebo-Acthar Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/95 (2.1%)		3/47 (6.4%)		1/25 (4%)		2/8 (25%)
Serious Adverse Events
	Arm A: RTP Acthar Gel		Arm B: RTP Placebo		Arm C: OLE Acthar Gel-Acthar Gel		Arm D: OLE Placebo-Acthar Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/95 (13.7%)		6/47 (12.8%)		4/25 (16%)		2/8 (25%)
Gastrointestinal disorders
Constipation	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
General disorders
Gait disturbance	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Infections and infestations
Pneumonia	6/95 (6.3%)	6	0/47 (0%)	0	1/25 (4%)	1	1/8 (12.5%)	1
Cellulitis staphylococcal	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Empyema	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Gastroenteritis	0/95 (0%)	0	1/47 (2.1%)	1	0/25 (0%)	0	0/8 (0%)	0
Pyelonephritis acute	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Respiratory tract infection	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Urosepsis	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Injury, poisoning and procedural complications
Procedural pain	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Rib fracture	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Fall	0/95 (0%)	0	0/47 (0%)	0	1/25 (4%)	1	0/8 (0%)	0
Femur fracture	0/95 (0%)	0	0/47 (0%)	0	1/25 (4%)	1	0/8 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Failure to thrive	0/95 (0%)	0	1/47 (2.1%)	1	0/25 (0%)	0	0/8 (0%)	0
Nervous system disorders
Amyotrophic lateral sclerosis	0/95 (0%)	0	1/47 (2.1%)	1	1/25 (4%)	1	1/8 (12.5%)	1
Cerebellar infarction	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Psychiatric disorders
Anxiety	0/95 (0%)	0	1/47 (2.1%)	1	0/25 (0%)	0	0/8 (0%)	0
Depression	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Mental status changes	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Suicidal ideation	0/95 (0%)	0	0/47 (0%)	0	1/25 (4%)	1	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/95 (2.1%)	2	1/47 (2.1%)	1	0/25 (0%)	0	0/8 (0%)	0
Respiratory failure	2/95 (2.1%)	2	1/47 (2.1%)	1	1/25 (4%)	1	0/8 (0%)	0
Pneumonia aspiration	1/95 (1.1%)	1	1/47 (2.1%)	1	0/25 (0%)	0	0/8 (0%)	0
Pulmonary embolism	2/95 (2.1%)	2	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Respiratory arrest	1/95 (1.1%)	1	1/47 (2.1%)	1	0/25 (0%)	0	0/8 (0%)	0
Dyspnoea	0/95 (0%)	0	1/47 (2.1%)	1	0/25 (0%)	0	0/8 (0%)	0
Haemothorax	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Pleural effusion	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Vascular disorders
Deep vein thrombosis	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Hypertensive emergency	1/95 (1.1%)	1	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A: RTP Acthar Gel		Arm B: RTP Placebo		Arm C: OLE Acthar Gel-Acthar Gel		Arm D: OLE Placebo-Acthar Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/95 (74.7%)		34/47 (72.3%)		18/25 (72%)		7/8 (87.5%)
Cardiac disorders
Tachycardia	0/95 (0%)	0	0/47 (0%)	0	2/25 (8%)	2	0/8 (0%)	0
Ear and labyrinth disorders
Excessive cerumen production	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Gastrointestinal disorders
Constipation	13/95 (13.7%)	15	4/47 (8.5%)	5	2/25 (8%)	3	2/8 (25%)	2
Dry Mouth	5/95 (5.3%)	5	0/47 (0%)	0	1/25 (4%)	1	1/8 (12.5%)	1
Dysphagia	5/95 (5.3%)	5	5/47 (10.6%)	5	0/25 (0%)	0	1/8 (12.5%)	1
Nausea	5/95 (5.3%)	6	2/47 (4.3%)	2	2/25 (8%)	2	1/8 (12.5%)	1
Salivary hypersecretion	5/95 (5.3%)	6	1/47 (2.1%)	1	0/25 (0%)	0	1/8 (12.5%)	1
Diarrhoea	0/95 (0%)	0	0/47 (0%)	0	1/25 (4%)	1	1/8 (12.5%)	1
Gastrooesophageal reflux disease	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	2/8 (25%)	2
Inflammatory bowel disease	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Vomiting	0/95 (0%)	0	0/47 (0%)	0	2/25 (8%)	2	0/8 (0%)	0
General disorders
Asthenia	6/95 (6.3%)	7	4/47 (8.5%)	5	1/25 (4%)	1	1/8 (12.5%)	1
Fatigue	13/95 (13.7%)	14	6/47 (12.8%)	8	3/25 (12%)	3	1/8 (12.5%)	1
Injection site bruising	13/95 (13.7%)	16	4/47 (8.5%)	6	0/25 (0%)	0	0/8 (0%)	0
Oedema	5/95 (5.3%)	5	1/47 (2.1%)	1	0/25 (0%)	0	0/8 (0%)	0
Oedema peripheral	17/95 (17.9%)	24	2/47 (4.3%)	2	2/25 (8%)	2	2/8 (25%)	2
Chest pain	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Pain	0/95 (0%)	0	0/47 (0%)	0	2/25 (8%)	2	1/8 (12.5%)	1
Infections and infestations
Gastroenteritis viral	2/95 (2.1%)	2	3/47 (6.4%)	3	0/25 (0%)	0	0/8 (0%)	0
Urinary tract infection	8/95 (8.4%)	12	2/47 (4.3%)	2	4/25 (16%)	6	0/8 (0%)	0
Bronchitis	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Nasopharyngitis	0/95 (0%)	0	0/47 (0%)	0	2/25 (8%)	2	0/8 (0%)	0
Oral candidiasis	0/95 (0%)	0	0/47 (0%)	0	3/25 (12%)	4	0/8 (0%)	0
Sinusitis	0/95 (0%)	0	0/47 (0%)	0	1/25 (4%)	1	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Contusion	9/95 (9.5%)	14	2/47 (4.3%)	4	2/25 (8%)	2	0/8 (0%)	0
Fall	18/95 (18.9%)	28	14/47 (29.8%)	33	6/25 (24%)	11	1/8 (12.5%)	1
Laceration	1/95 (1.1%)	1	3/47 (6.4%)	3	0/25 (0%)	0	0/8 (0%)	0
Limb injury	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Investigations
Blood pressure increased	5/95 (5.3%)	7	1/47 (2.1%)	1	0/25 (0%)	0	1/8 (12.5%)	1
Weight decreased	3/95 (3.2%)	3	5/47 (10.6%)	6	1/25 (4%)	1	1/8 (12.5%)	1
Metabolism and nutrition disorders
Increased appetite	5/95 (5.3%)	6	0/47 (0%)	0	0/25 (0%)	0	0/8 (0%)	0
Abnormal loss of weight	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Decreased appetite	0/95 (0%)	0	0/47 (0%)	0	2/25 (8%)	2	0/8 (0%)	0
Diabetes mellitus	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	8/95 (8.4%)	16	4/47 (8.5%)	8	0/25 (0%)	0	1/8 (12.5%)	1
Muscle atrophy	2/95 (2.1%)	3	3/47 (6.4%)	5	3/25 (12%)	3	0/8 (0%)	0
Muscle spasms	15/95 (15.8%)	16	3/47 (6.4%)	3	2/25 (8%)	3	0/8 (0%)	0
Muscular weakness	22/95 (23.2%)	35	9/47 (19.1%)	14	3/25 (12%)	3	2/8 (25%)	2
Musculoskeletal pain	4/95 (4.2%)	6	7/47 (14.9%)	7	0/25 (0%)	0	0/8 (0%)	0
Neck Pain	5/95 (5.3%)	5	1/47 (2.1%)	1	0/25 (0%)	0	1/8 (12.5%)	1
Pain in extremity	3/95 (3.2%)	3	3/47 (6.4%)	4	1/25 (4%)	1	2/8 (25%)	2
Back pain	0/95 (0%)	0	0/47 (0%)	0	1/25 (4%)	1	2/8 (25%)	2
Bursitis	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Mobility decreased	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Nervous system disorders
Dizziness	7/95 (7.4%)	7	3/47 (6.4%)	3	0/25 (0%)	0	1/8 (12.5%)	1
Dysarthria	9/95 (9.5%)	12	4/47 (8.5%)	5	0/25 (0%)	0	0/8 (0%)	0
Headache	11/95 (11.6%)	14	1/47 (2.1%)	6	1/25 (4%)	1	2/8 (25%)	2
Muscle contractions involuntary	3/95 (3.2%)	3	3/47 (6.4%)	3	2/25 (8%)	2	0/8 (0%)	0
Tremor	0/95 (0%)	0	0/47 (0%)	0	2/25 (8%)	2	0/8 (0%)	0
Psychiatric disorders
Anxiety	6/95 (6.3%)	6	2/47 (4.3%)	3	1/25 (4%)	1	1/8 (12.5%)	1
Depression	3/95 (3.2%)	4	3/47 (6.4%)	3	0/25 (0%)	0	0/8 (0%)	0
Insomnia	7/95 (7.4%)	7	1/47 (2.1%)	1	2/25 (8%)	3	2/8 (25%)	2
Renal and urinary disorders
Dysuria	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	9/95 (9.5%)	10	6/47 (12.8%)	8	1/25 (4%)	1	2/8 (25%)	2
Chronic respiratory failure	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Cough	0/95 (0%)	0	0/47 (0%)	0	3/25 (12%)	3	2/8 (25%)	2
Dyspnoea exertional	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Increased viscosity of upper respiratory secretion	0/95 (0%)	0	0/47 (0%)	0	2/25 (8%)	2	0/8 (0%)	0
Respiratory disorder	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Ecchymosis	5/95 (5.3%)	5	2/47 (4.3%)	3	0/25 (0%)	0	0/8 (0%)	0
Blister	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Rash	0/95 (0%)	0	0/47 (0%)	0	1/25 (4%)	1	1/8 (12.5%)	1
Skin discolouration	0/95 (0%)	0	0/47 (0%)	0	0/25 (0%)	0	1/8 (12.5%)	1
Vascular disorders
Hypertension	8/95 (8.4%)	10	1/47 (2.1%)	1	1/25 (4%)	1	1/8 (12.5%)	1
Hot flush	0/95 (0%)	0	0/47 (0%)	0	2/25 (8%)	2	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.