Acthar Gel in Participants With Pulmonary Sarcoidosis | NCT03320070

Label	Type	Description	Intervention Names
Acthar Gel in DBT Then Acthar Gel in OLE	Experimental	Participants received Acthar Gel as a 1 milliliter (mL) injection under the skin, twice weekly, for 24 weeks in the double-blind treatment (DBT) phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the optional open-label extension (OLE) phase.	Drug: Acthar Gel
Placebo in DBT Then Acthar Gel in OLE	Experimental	Participants received Acthar Gel matching placebo as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the optional OLE phase.	Drug: Acthar Gel Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Acthar Gel	Drug	Acthar Gel for subcutaneous (SC) injection (80 units per 1 mL)	Acthar Gel in DBT Then Acthar Gel in OLE Placebo in DBT Then Acthar Gel in OLE

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
DBT: Number of Participants in Each Category of Assessment Based on Forced Vital Capacity (FVC), a Pulmonary Function Test Parameter at Week 24	Forced vital capacity (FVC) is a pulmonary function test parameter that indicates the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It's measured by spirometry, which is a common breathing test to check lung function. Based on the absolute change of percent predicted, FVC was evaluated to determine if the condition is: Improved (+1) [≥ 5% absolute change] Unchanged (0) [>- 5% to < 5% absolute change], or Worse (-1) [≤ -5% absolute change] An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.	Week 24
OLE: Number of Participants in Each Category of Assessment Based on FVC, a Pulmonary Function Test Parameter at Week 48	Forced vital capacity (FVC) is a pulmonary function test parameter that indicates the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It's measured by spirometry, which is a common breathing test to check lung function. Based on the absolute change of percent predicted, FVC was evaluated to determine if the condition is: Improved (+1) [≥ 5% absolute change] Unchanged (0) [>- 5% to < 5% absolute change], or Worse (-1) [≤ -5% absolute change] An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.	Week 48
DBT: Number of Participants in Each Category of Assessment Based on the Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO), a Pulmonary Function Test Parameter at Week 24	The diffusing capacity of the lungs for carbon monoxide (DLCO) measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in the blood. Participants are asked to fully inhale a low concentration of carbon monoxide and an inert tracer gas. Based on the absolute change of percent predicted, DLCO was evaluated to determine if the condition is: Improved (+1) [≥ 5% absolute change] Unchanged (0) [>- 5% to < 5% absolute change], Worse (-1) [≤ -5% absolute change] An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

Name	Affiliation	Role
Clinical Team Leader	Mallinckrodt	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
UAB Lung Health Center		Birmingham	Alabama	35294	United States
David Geffen School of Medicine

PubMed Identifier	Type	Citation	Retractions
37072607	Derived	Mirsaeidi M, Baughman RP, Sahoo D, Tarau E. Results From a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis. Pulm Ther. 2023 Jun;9(2):237-253. doi: 10.1007/s41030-023-00222-2. Epub 2023 Apr 19.

ID	Title	Description
FG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 milliliter (mL) injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 18, 2020	Nov 11, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

DBT: Number of Participants in Each Category of Assessment Based on Forced Vital Capacity (FVC), a Pulmonary Function Test Parameter at Week 24

Forced vital capacity (FVC) is a pulmonary function test parameter that indicates the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It's measured by spirometry, which is a common breathing test to check lung function. Based on the absolute change of percent predicted, FVC was evaluated to determine if the condition is:

Improved (+1) [≥ 5% absolute change]
Unchanged (0) [>- 5% to < 5% absolute change], or
Worse (-1) [≤ -5% absolute change]

An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

The mITT population included all randomized participants who received at least 1 dose of the IMP and who contributed any efficacy data to the study.

Posted

Count of Participants

Participants

Week 24

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE	Participants received Acthar Gel matching placebo as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.

Units	Counts
Participants	OG00027 OG00128

Title

Denominators

Categories

Improved

Title	Measurements
	OG00010 OG0017

Unchanged

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Chi-squared		0.5076														Superiority

Primary

OLE: Number of Participants in Each Category of Assessment Based on FVC, a Pulmonary Function Test Parameter at Week 48

Improved (+1) [≥ 5% absolute change]
Unchanged (0) [>- 5% to < 5% absolute change], or
Worse (-1) [≤ -5% absolute change]

An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

Open-label safety population included participants who continued into the OLE phase and received at least one dose of IMP during the OLE phase

Posted

Count of Participants

Participants

Week 48

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE	Participants received Acthar Gel matching placebo as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.

Primary

DBT: Number of Participants in Each Category of Assessment Based on the Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO), a Pulmonary Function Test Parameter at Week 24

The diffusing capacity of the lungs for carbon monoxide (DLCO) measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in the blood. Participants are asked to fully inhale a low concentration of carbon monoxide and an inert tracer gas. Based on the absolute change of percent predicted, DLCO was evaluated to determine if the condition is:

Improved (+1) [≥ 5% absolute change]
Unchanged (0) [>- 5% to < 5% absolute change],
Worse (-1) [≤ -5% absolute change]

An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

The mITT population included all randomized participants who received at least 1 dose of the IMP and who contributed any efficacy data to the study.

Posted

Count of Participants

Participants

Week 24

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE	Participants received Acthar Gel matching placebo as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.

Primary

OLE: Number of Participants in Each Category of Assessment Based on the DLCO, a Pulmonary Function Test Parameter at Week 48

Improved (+1) [≥ 5% absolute change]
Unchanged (0) [>- 5% to < 5% absolute change],
Worse (-1) [≤ -5% absolute change]

An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

Open-label safety population included participants who continued into the OLE phase and received at least one dose of IMP during the OLE phase

Posted

Count of Participants

Participants

Week 48

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE	Participants received Acthar Gel matching placebo as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.

Primary

DBT: Number of Participants in Each Category of Assessment Based on High Resolution Computer Tomography (HRCT) at Week 24

High-resolution computer tomography (HRCT) is a type of computed tomography (CT) with specific techniques to enhance image resolution. It is used in the diagnosis of various health problems, most commonly for lung disease. These images show cross sections (slices) through the lungs. HRCT imaging was evaluated by the investigator/radiologist and the central reader to determine if the condition is improved (+1), unchanged (0), or worse (-1). An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

The mITT population included all randomized participants who received at least 1 dose of the IMP and who contributed any efficacy data to the study.

Posted

Count of Participants

Participants

Week 24

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE	Participants received Acthar Gel matching placebo as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.

Primary

OLE: Number of Participants in Each Category of Assessment Based on HRCT at Week 48

Open-label safety population included participants who continued into the OLE phase and received at least one dose of IMP during the OLE phase

Posted

Count of Participants

Participants

Week 48

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE	Participants received Acthar Gel matching placebo as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.

Primary

DBT: Number of Participants in Each Category of Assessment Based on the King's Sarcoidosis Questionnaire (KSQ) (General Health), a Quality of Life Parameter at Week 24

King's sarcoidosis questionnaire (KSQ) (General Health) is a 28-item questionnaire for participants to indicate the status of their sarcoidosis and treatment. Each item was answered on a 7-point scale where 1 means the participant experiences the symptom all the time and 7 means the participant does not experience the symptom at all. Higher scores indicate improvement, and a change of 4 points is considered clinically meaningful. The score on the scale was evaluated to determine if the condition is:

Improved (+1) based on a change of ≥ 4 points
Unchanged (0) based on a change of >- 4 to < 4 points
Worse (-1) based on a change of ≤ -4 points

An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

The mITT population included all randomized participants who received at least 1 dose of the IMP and who contributed any efficacy data to the study.

Posted

Count of Participants

Participants

Week 24

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE

Primary

OLE: Number of Participants in Each Category of Assessment Based on the KSQ (General Health), a Quality of Life Parameter at Week 48

Improved (+1) based on a change of ≥ 4 points
Unchanged (0) based on a change of >- 4 to < 4 points
Worse (-1) based on a change of ≤ -4 points

An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

Open-label safety population included participants who continued into the OLE phase and received at least one dose of IMP during the OLE phase.

Posted

Count of Participants

Participants

Week 48

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE

Primary

DBT: Number of Participants in Each Category of Assessment Based on the Fatigue Assessment Score (FAS), a Quality of Life Parameter at Week 24

The fatigue assessment score (FAS) is a 10-item checklist for participants to indicate the level of their fatigue. Each item was answered on a 5-point scale where 1 means the participant does not experience the symptom all and 5 means the participant experiences the symptom all the time. Lower scores indicate improvement (less fatigue) and a change of 4 points is considered clinically meaningful. The score on the scale was evaluated to determine if the condition is:

Improved (+1) based on a change of ≤ -4 points
Unchanged (0) based on a change of >- 4 to < 4 points
Worse (-1) based on a change of ≥ 4 points

An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

The mITT population included all randomized participants who received at least 1 dose of the IMP and who contributed any efficacy data to the study.

Posted

Count of Participants

Participants

Week 24

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE

Primary

OLE: Number of Participants in Each Category of Assessment Based on FAS, a Quality of Life Parameter at Week 48

Improved (+1) based on a change of ≤ -4 points
Unchanged (0) based on a change of >- 4 to < 4 points
Worse (-1) based on a change of ≥ 4 points

An additional category "Missing Assessment" indicates the participants who had a missing assessment for this outcome measure.

Open-label safety population included participants who continued into the OLE phase and received at least one dose of IMP during the OLE phase.

Posted

Count of Participants

Participants

Week 48

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
OG001	Placebo in DBT Then Acthar Gel in OLE

Primary

DBT: Number of Participants in Each Category of Assessment Based on Corticosteroid Taper Score in Participants Receiving Each Dose of Prednisone at Week 24

Corticosteroids are first line treatment for sarcoidosis. Concerns of corticosteroid toxicity led to efforts to taper dose sooner. Participants were clinically evaluated at each visit by investigator and categorized by their condition; dose was tapered using algorithm to take them off prednisone using incremental doses of 40,30,20,10,7.5,5,2.5,0 mg, as explained with each category below.

Improved: When condition improved, reduce dose by 1 level
Unchanged:
1. When stable condition without toxicity: At first stable visit they continue same dose; at second stable visit, reduce dose by 1 level
2. When stable condition with toxicity: toxicity is treated; reduce dose by 1 level
Deteriorate: When worsening condition, increase dose by 1 or 2 levels but not >40mg/day

Dose tapering was done based on the participant's clinical condition.

Category "Missing Assessment" indicates participants who had a missing assessment for this outcome measure.

The mITT population included all randomized participants who received at least 1 dose of the IMP and who contributed any efficacy data to the study.

Posted

Count of Participants

Participants

Week 24

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.

Primary

OLE: Number of Participants in Each Category of Assessment Based on Corticosteroid Taper Score in Participants Receiving Each Dose of Prednisone at Week 48

Improved: When condition improved, reduce dose by 1 level
Unchanged:
1. When stable condition without toxicity: At first stable visit they continue same dose; at second stable visit, reduce dose by 1 level
2. When stable condition with toxicity: toxicity is treated; reduce dose by 1 level
Deteriorate: When worsening condition, increase dose by 1 or 2 levels but not >40mg/day

Dose tapering was done based on the participant's clinical condition.

Category "Missing Assessment" indicates participants who had a missing assessment for this outcome measure.

Open-label safety population included participants who continued into the OLE phase and received at least one dose of IMP during the OLE phase.

Posted

Count of Participants

Participants

Week 48

ID	Title	Description
OG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Uveitis	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG0030 affected25 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Influenza	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0011 affected28 at risk EG0020 affected22 at risk EG003
Pelvic abscess	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0011 affected28 at risk EG0020 affected22 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0011 affected28 at risk EG0021 affected22 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0011 affected28 at risk EG0020 affected22 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0010 affected28 at risk EG0021 affected22 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0010 affected28 at risk EG0021 affected22 at risk EG003
Metastatic renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0010 affected28 at risk EG0021 affected22 at risk EG003
Idiopathic pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0010 affected28 at risk EG0021 affected22 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0010 affected28 at risk EG0021 affected22 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0010 affected28 at risk EG0021 affected22 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0010 affected28 at risk EG0021 affected22 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dry eye	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG0030 affected25 at risk
Ocular hyperaemia	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0010 affected28 at risk EG0022 affected22 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0022 affected22 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0011 affected28 at risk EG0021 affected22 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0012 affected28 at risk EG0023 affected22 at risk EG003
Chest discomfort	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0011 affected28 at risk EG0021 affected22 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0004 affected27 at risk EG0014 affected28 at risk EG0022 affected22 at risk EG003
Injection site bruising	General disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0015 affected28 at risk EG0021 affected22 at risk EG003
Injection site swelling	General disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Oedema peripheral	General disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected27 at risk EG0012 affected28 at risk EG0021 affected22 at risk EG003
Peripheral swelling	General disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Sarcoidosis	Immune system disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected27 at risk EG0011 affected28 at risk EG0020 affected22 at risk EG003
Bronchitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0012 affected28 at risk EG0023 affected22 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0011 affected28 at risk EG0020 affected22 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0012 affected28 at risk EG0020 affected22 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0005 affected27 at risk EG0012 affected28 at risk EG0021 affected22 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0011 affected28 at risk EG0020 affected22 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0003 affected27 at risk EG0011 affected28 at risk EG0020 affected22 at risk EG003
C-reactive protein increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0010 affected28 at risk EG0022 affected22 at risk EG003
Weight increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0011 affected28 at risk EG0021 affected22 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0006 affected27 at risk EG0011 affected28 at risk EG0021 affected22 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0012 affected28 at risk EG0020 affected22 at risk EG003
Obesity	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0018 affected28 at risk EG0022 affected22 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0013 affected28 at risk EG0021 affected22 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0013 affected28 at risk EG0020 affected22 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0010 affected28 at risk EG0022 affected22 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0012 affected28 at risk EG0020 affected22 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected27 at risk EG0011 affected28 at risk EG0021 affected22 at risk EG003
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0004 affected27 at risk EG0017 affected28 at risk EG0021 affected22 at risk EG003
Depression	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0022 affected22 at risk EG003
Polyuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0010 affected28 at risk EG0020 affected22 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0011 affected28 at risk EG0020 affected22 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0015 affected28 at risk EG0023 affected22 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0013 affected28 at risk EG0022 affected22 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0011 affected28 at risk EG0021 affected22 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected27 at risk EG0012 affected28 at risk EG0021 affected22 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0012 affected28 at risk EG0020 affected22 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected27 at risk EG0012 affected28 at risk EG0020 affected22 at risk EG003
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected27 at risk EG0011 affected28 at risk EG0020 affected22 at risk EG003

ID	Term
D017563	Lung Diseases, Interstitial
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D012507	Sarcoidosis
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D006968	Hypersensitivity, Delayed
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Title	Description
BG000	Acthar Gel in DBT Then Acthar Gel in OLE	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
BG001	Placebo in DBT Then Acthar Gel in OLE	Participants received Acthar Gel matching placebo as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase. Participants, who chose to continue into the optional OLE phase, then received Acthar Gel as a 1 mL injection under the skin, twice weekly, for another 24 weeks in the OLE phase.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	DBT: Acthar Gel 80 U (1 mL)	Participants received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase.	27	4	27	22	27
EG001	DBT: Placebo	Participants received Acthar Gel matching placebo as a 1 mL injection under the skin, twice weekly, for 24 weeks in the DBT phase.	28	3	28	25	28
EG002	OLE: Acthar Gel 80 U (1 mL) [Received Acthar in DBT]	Participants who received Acthar Gel in the DBT phase and opted to continue treatment in OLE phase, received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the OLE phase.	22	6	22	14	22
EG003	OLE: Acthar Gel 80 U (1 mL) [Received Placebo in DBT]	Participants who received Acthar Gel matching placebo in the DBT phase and opted to continue treatment in OLE phase, received Acthar Gel as a 1 mL injection under the skin, twice weekly, for 24 weeks in the OLE phase.	25	0	25	14	25