Acthar Gel for Active Systemic Lupus Erythematosus (SLE)

• ClinicalTrials.gov Identifier: NCT02953821
• Recruitment Status: Completed
• First Posted: November 3, 2016
• Results First Posted: August 20, 2020
• Last Update Posted: August 20, 2020
• Sponsor: Mallinckrodt
• Information provided by (Responsible Party): Mallinckrodt

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Lupus Erythematosus, Systemic
• Interventions: Drug: Acthar Gel; Drug: Placebo Gel
• Enrollment: 172

Participant Flow

Recruitment Details
Pre-assignment Details	Of 293 who signed informed consent, 172 were randomized into treatment groups

Arm/Group Title	Placebo Gel	Acthar Gel
Arm/Group Description	Participants receive Placebo Gel every other day for 4 weeks, and then twice per week for 20 weeks Placebo Gel: 1 mL (0 Units) given by a shot under the skin (via subcutaneous injection)	Participants receive Acthar Gel every other day for 4 weeks, and then twice per week for 20 weeks Acthar Gel: 1 mL (80 Units) given by a shot under the skin (via subcutaneous injection)
Period Title: Overall Study
Started	86	86
Safety Population	86	86
Modified Intent to Treat (mITT) Populati	85	84
Per Protocol (PP) Population	72	75
Completed Week 16 Visit	76	77
Completed Study Treatment (Week 24)	73	76
Completed [1]	71	73
Not Completed	15	13
Reason Not Completed
Adverse Event	0	4
Death	1	0
Progressive Disease	5	1
Lost to Follow-up	2	0
Physician Decision	1	1
Withdrawal by Subject	3	3
Change of address	0	1
Lack of Efficacy	1	0
Out of state for indeterminate time	0	1
No improvement	0	1
Refused follow-up visit	2	1
[1] including follow-up

Baseline Characteristics

Arm/Group Title		Placebo Gel	Acthar Gel	Total
Arm/Group Description		Participants receive Placebo Gel every other day for 4 weeks, and then twice per week for 20 weeks Placebo Gel: 1 mL (0 Units) given by a shot under the skin (via subcutaneous injection)	Participants receive Acthar Gel every other day for 4 weeks, and then twice per week for 20 weeks Acthar Gel: 1 mL (80 Units) given by a shot under the skin (via subcutaneous injection)	Total of all reporting groups
Overall Number of Baseline Participants		86	86	172
Baseline Analysis Population Description		Safety Population (except for study-specific measures)
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	86 participants	86 participants	172 participants
		39.3 (12.99)	40.1 (12.45)	39.7 (12.69)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	86 participants	86 participants	172 participants
	Female	82 95.3%	76 88.4%	158 91.9%
	Male	4 4.7%	10 11.6%	14 8.1%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	86 participants	86 participants	172 participants
	American Indian or Alaska Native	19 22.1%	19 22.1%	38 22.1%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	8 9.3%	9 10.5%	17 9.9%
	White	30 34.9%	33 38.4%	63 36.6%
	More than one race	29 33.7%	25 29.1%	54 31.4%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Physician's Global Assessment (PGA)
Description	PGA is a 100 mm visual analogue scale where higher scores indicate more severe disease activity. Lower scores indicate improvement.
Time Frame	Baseline, Week 16, Week 24

Outcome Measure Data

Analysis Population Description

mITT population with score at the given week

Arm/Group Title		Placebo Gel	Acthar Gel
Arm/Group Description:		Participants receive Placebo Gel every other day for 4 weeks, and then twice per week for 20 weeks Placebo Gel: 1 mL (0 Units) given by a shot under the skin (via subcutaneous injection)	Participants receive Acthar Gel every other day for 4 weeks, and then twice per week for 20 weeks Acthar Gel: 1 mL (80 Units) given by a shot under the skin (via subcutaneous injection)
Overall Number of Participants Analyzed		85	84
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	Number Analyzed	85 participants	84 participants
		58.8 (15.81)	60.6 (16.69)
Week 16	Number Analyzed	76 participants	77 participants
		33.2 (18.77)	30.2 (14.89)
Week 24	Number Analyzed	73 participants	76 participants
		26.9 (17.76)	25.5 (17.22)

2. Primary Outcome

Title	British Isles Lupus Assessment Group 2004 (BILAG 2004)
Description	BILAG records disease activity occurring over the past 4 weeks, and is used to determine whether different course of treatment is required. The BILAG-2004 index covers 97 signs/symptoms across 9 organ systems. Each question is answered as 0-not present, 1-improving, 2-same, 3-worse, or 4-new. The BILAG-2004 index categorizes disease activity in each organ system into five different levels from A to E. Grade A represents very active disease, Grade B represents moderate disease activity, Grade C indicates mild stable disease, and grade D implies no disease activity, but suggests the organ system had previously been affected. Grade E indicates no current or previous disease activity. A score is applied to each grade of each organ system using coding scheme of A=12, B=8, C=1, and D/E=0 and is summarized as a total score ranging 0-108. Higher scores indicate more severe disease activity.
Time Frame	Baseline, Week 16, Week 24

Outcome Measure Data

Analysis Population Description

mITT population with a score at the given week

Arm/Group Title		Placebo Gel	Acthar Gel
Arm/Group Description:		Participants receive Placebo Gel every other day for 4 weeks, and then twice per week for 20 weeks Placebo Gel: 1 mL (0 Units) given by a shot under the skin (via subcutaneous injection)	Participants receive Acthar Gel every other day for 4 weeks, and then twice per week for 20 weeks Acthar Gel: 1 mL (80 Units) given by a shot under the skin (via subcutaneous injection)
Overall Number of Participants Analyzed		85	84
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	Number Analyzed	85 participants	84 participants
		18.2 (5.15)	18.0 (5.45)
Week 16	Number Analyzed	76 participants	77 participants
		9.7 (6.57)	7.7 (5.91)
Week 24	Number Analyzed	73 participants	76 participants
		8.0 (6.21)	6.9 (5.87)

3. Primary Outcome

Title	Number of Participants With at Least a 4 Point Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K)
Description	The SLEDAI-2K is a modified version of a composite score based on the presence or absence of clinical signs, clinical symptoms, and immunologic laboratory results taken within 10 days of the evaluations. Each of the descriptors has a weighted score and the total score of SLEDAI-2K is the sum of all 24 descriptor scores. The total SLEDAI-2K score falls between 0 and 105, with higher scores representing higher disease activity. Decrease from baseline indicates improvement.
Time Frame	Week 16, Week 24

Outcome Measure Data

Analysis Population Description

modified Intent to Treat (mITT)

Arm/Group Title	Placebo Gel	Acthar Gel
Arm/Group Description:	Participants receive Placebo Gel every other day for 4 weeks, and then twice per week for 20 weeks Placebo Gel: 1 mL (0 Units) given by a shot under the skin (via subcutaneous injection)	Participants receive Acthar Gel every other day for 4 weeks, and then twice per week for 20 weeks Acthar Gel: 1 mL (80 Units) given by a shot under the skin (via subcutaneous injection)
Overall Number of Participants Analyzed	85	84
Measure Type: Count of Participants; Unit of Measure: Participants
Week 16	40 47.1%	41 48.8%
Week 24	46 54.1%	44 52.4%

4. Secondary Outcome

Title	Number of Participants With Severe Flare, Based on the SELENA Flare Index (SFI) at Week 16
Description	Among some adults, having a period of SLE symptoms-called flares-may happen every so often, sometimes even years apart, and go away at other times-called remission. The SFI categorizes SLE flares as mild, moderate or severe.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Placebo Gel	Acthar Gel
Arm/Group Description:	Participants receive Placebo Gel	Participants receive Acthar Gel
Overall Number of Participants Analyzed	85	84
Measure Type: Count of Participants; Unit of Measure: Participants
	3 3.5%	0 0.0%

5. Secondary Outcome

Title	Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score
Description	The CLASI total activity score reflects ongoing inflammation that can be treated, with points given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Mild, moderate, and severe disease correspond with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Higher scores indicate more disease activity, lower scores indicate improvement.
Time Frame	at Baseline and Weeks 4, 8, and 16

Outcome Measure Data

Analysis Population Description

mITT population with scores at the given week

Arm/Group Title		Placebo Gel	Acthar Gel
Arm/Group Description:		Participants receive Placebo Gel	Participants receive Acthar Gel
Overall Number of Participants Analyzed		85	84
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	Number Analyzed	84 participants	82 participants
		7.1 (6.53)	7.9 (7.48)
Week 4	Number Analyzed	82 participants	81 participants
		5.8 (5.57)	5.6 (5.30)
Week 8	Number Analyzed	82 participants	78 participants
		5.0 (5.19)	5.0 (5.41)
Week 12	Number Analyzed	77 participants	78 participants
		4.5 (5.41)	4.0 (4.08)
Week 16	Number Analyzed	75 participants	75 participants
		3.8 (4.36)	3.4 (3.77)

6. Secondary Outcome

Title	Mean Number of Swollen or Tender Joints on the 28-Joint Count
Description	The 28 Joint Count includes assessment of swelling and tenderness in the shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and knees. The investigator counts how many of the 28 joints are swollen or tender at the given week.
Time Frame	at Baseline and at Weeks 4, 8, 12 and 16

Outcome Measure Data

Analysis Population Description

mITT population with tender and swollen joints at the given week

Arm/Group Title		Placebo Gel	Acthar Gel
Arm/Group Description:		Participants receive Placebo Gel	Participants receive Acthar Gel
Overall Number of Participants Analyzed		85	84
Overall Number of Units Analyzed; Type of Units Analyzed: Joints		28	28
Mean (Standard Deviation); Unit of Measure: Joints
Baseline	Number Analyzed	28 Joints [1]	28 Joints [2]
		7.2 (4.98)	8.2 (5.85)
Week 4	Number Analyzed	28 Joints [3]	28 Joints [2]
		4.9 (4.77)	4.2 (4.24)
Week 8	Number Analyzed	28 Joints [3]	28 Joints [4]
		3.8 (4.97)	2.9 (3.42)
Week 12	Number Analyzed	28 Joints [5]	28 Joints [4]
		2.9 (4.40)	2.3 (3.00)
Week 16	Number Analyzed	28 Joints [6]	28 Joints [6]
		2.8 (3.67)	1.9 (3.20)

[1]

84 participants

[2]

81 participants

[3]

82 participants

[4]

78 participants

[5]

77 participants

[6]

75 participants

7. Secondary Outcome

Title	Number of Participants With Decrease in Prednisone Dose to < 7.5 mg/Day at Week 20 and Week 24
Description	[Not Specified]
Time Frame	Week 20, Week 24

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Placebo Gel	Acthar Gel
Arm/Group Description:	Participants receive Placebo Gel	Participants receive Acthar Gel
Overall Number of Participants Analyzed	85	84
Measure Type: Count of Participants; Unit of Measure: Participants
Week 20	5 5.9%	3 3.6%
Week 24	6 7.1%	4 4.8%

Adverse Events

Time Frame	24 Weeks
Adverse Event Reporting Description	A Treatment-Emergent Adverse Event (TEAE) is defined as an undesirable event that begins or worsens after the first dose of study drug and no later than follow up visit date or no more than 28 days after the last dose of study drug if the follow up visit date is missing. TEAEs were collected in the safety population.
Arm/Group Title	Placebo Gel		Acthar Gel
Arm/Group Description	Participants receive Placebo Gel		Participants receive Acthar Gel
All-Cause Mortality
	Placebo Gel		Acthar Gel
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/86 (1.16%)		0/86 (0.00%)
Serious Adverse Events
	Placebo Gel		Acthar Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/86 (9.30%)		4/86 (4.65%)
Blood and lymphatic system disorders
Thrombocytopenia † 1	1/86 (1.16%)		0/86 (0.00%)
Infections and infestations
Appendicitis † 1	1/86 (1.16%)		0/86 (0.00%)
Gastroenteritis † 1	1/86 (1.16%)		0/86 (0.00%)
Herpes zoster † 1	0/86 (0.00%)		1/86 (1.16%)
Peritonitis † 1	1/86 (1.16%)		0/86 (0.00%)
Pneumonia † 1	1/86 (1.16%)		0/86 (0.00%)
Pyelonephritis † 1	1/86 (1.16%)		0/86 (0.00%)
Soft tissue infection † 1	1/86 (1.16%)		0/86 (0.00%)
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus † 1	1/86 (1.16%)		2/86 (2.33%)
Psychiatric disorders
Drug abuse † 1	1/86 (1.16%)		0/86 (0.00%)
Renal and urinary disorders
Nephrotic syndrome † 1	0/86 (0.00%)		1/86 (1.16%)
1 Term from vocabulary, MedDRA (19.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo Gel		Acthar Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/86 (26.74%)		31/86 (36.05%)
Infections and infestations
Nasopharyngitis † 1	6/86 (6.98%)	6	3/86 (3.49%)	3
Upper respiratory tract infection † 1	1/86 (1.16%)	1	9/86 (10.47%)	10
Urinary tract infection † 1	10/86 (11.63%)	13	6/86 (6.98%)	6
Nervous system disorders
Headache † 1	5/86 (5.81%)	6	6/86 (6.98%)	9
Psychiatric disorders
Insomnia † 1	4/86 (4.65%)	4	7/86 (8.14%)	7
Vascular disorders
Hypertension † 1	0/86 (0.00%)	0	6/86 (6.98%)	6
1 Term from vocabulary, MedDRA (19.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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.

Results Point of Contact

• Name/Title: Medical Information Call Center
• Organization: Mallinckrodt
• Phone: 800-556-3314 ext 5
• EMail: clinicaltrials@mnk.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Askanase AD, Zhao E, Zhu J, Bilyk R, Furie RA. Repository Corticotropin Injection for Persistently Active Systemic Lupus Erythematosus: Results from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Rheumatol Ther. 2020 Dec;7(4):893-908. doi: 10.1007/s40744-020-00236-1. Epub 2020 Sep 29.

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT02953821
• Other Study ID Numbers: MNK14304067
• First Submitted: November 1, 2016
• First Posted: November 3, 2016
• Results First Submitted: July 8, 2020
• Results First Posted: August 20, 2020
• Last Update Posted: August 20, 2020