Trial Outcomes & Findings for Acthar for Treatment of Proteinuria in Diabetic Nephropathy Patients (NCT NCT01601236)

NCT ID: NCT01601236

Last Updated: 2019-11-18

Results Overview

Percent change in eGFR at Visit 12 (Week 36) compared to average baseline eGFR obtained during screening

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

34 participants

Primary outcome timeframe

Visit 12 (Week 36)

Results posted on

2019-11-18

Participant Flow

Initial recruitment target was 40 subjects.

Adaptive design mandated closure of groups 5 \& 6 with re-assignment of subjects to groups 3 \& 4 if pre-defined tolerability criteria were met in 2 of first 6 patients.

Participant milestones

Participant milestones
Measure	Group 1: Acthar 8 U (0.1 mL) Daily H.P. Acthar Gel (repository corticotropin injection) administered via daily subcutaneous (SC) injection for 36 weeks	Group 2: Placebo (0.1 mL) Daily Placebo: contains the same inactive ingredients as H.P. Acthar Gel without the active pharmaceutical ingredient (API)administered via daily SC injection for 36 weeks	Group 3: Acthar 16 U (0.2 mL) Daily H.P. Acthar Gel (repository corticotropin injection) administered via daily SC injection for 36 weeks	Group 4: Placebo (0.2 mL) Daily Placebo: contains the same inactive ingredients as H.P. Acthar Gel without the API administered via daily SC injection for 36 weeks	Group 5: Acthar 32 U (0.4 mL) Daily H.P. Acthar Gel (repository corticotropin injection) administered via daily SC injection for 36 weeks	Group 6: Placebo (0.4 mL) Daily Placebo: contains the same inactive ingredients as H.P. Acthar Gel without the API administered via daily SC injection for 36 weeks
Overall Study COMPLETED	2	2	8	4	0	0
Overall Study STARTED	7	3	14	6	3	1
Overall Study NOT COMPLETED	5	1	6	2	3	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Acthar for Treatment of Proteinuria in Diabetic Nephropathy Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: Acthar 8 U (0.1 mL) Daily n=7 Participants Repository Corticotropin Injection Repository Corticotropin Injection: H.P. Acthar Gel (repository corticotropin injection) is administered via daily SC injection for 36 weeks in the three dose groups \[8 U (0.1 mL), 16 U (0.2 mL), or 32 U (0.4 mL)\].	Group 2: Placebo (0.1 mL) Daily n=3 Participants Placebo Placebo: Placebo contains the same inactive ingredients as H.P. Acthar Gel without the active pharmaceutical ingredient (API). Placebo is administered via daily SC injection for 36 weeks in equal volumes as the Acthar comparator volumes.	Group 3: Acthar 16 U (0.2 mL) Daily n=14 Participants Repository Corticotropin Injection Repository Corticotropin Injection: H.P. Acthar Gel (repository corticotropin injection) is administered via daily SC injection for 36 weeks in the three dose groups \[8 U (0.1 mL), 16 U (0.2 mL), or 32 U (0.4 mL)\].	Group 4: Placebo (0.2 mL) Daily n=6 Participants Placebo Placebo: Placebo contains the same inactive ingredients as H.P. Acthar Gel without the active pharmaceutical ingredient (API). Placebo is administered via daily SC injection for 36 weeks in equal volumes as the Acthar comparator volumes.	Group 5: Acthar 32 U (0.4 mL) Daily n=3 Participants Repository Corticotropin Injection Repository Corticotropin Injection: H.P. Acthar Gel (repository corticotropin injection) is administered via daily SC injection for 36 weeks in the three dose groups \[8 U (0.1 mL), 16 U (0.2 mL), or 32 U (0.4 mL)\].	Group 6: Placebo (0.4 mL) Daily n=1 Participants Placebo Placebo: Placebo contains the same inactive ingredients as H.P. Acthar Gel without the active pharmaceutical ingredient (API). Placebo is administered via daily SC injection for 36 weeks in equal volumes as the Acthar comparator volumes.	Total n=34 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants	5 Participants n=4 Participants	2 Participants n=21 Participants	0 Participants n=8 Participants	24 Participants n=8 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	10 Participants n=8 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	0 Participants n=7 Participants	9 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	15 Participants n=8 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=8 Participants	19 Participants n=8 Participants
Region of Enrollment United States	7 participants n=5 Participants	3 participants n=7 Participants	14 participants n=5 Participants	6 participants n=4 Participants	3 participants n=21 Participants	1 participants n=8 Participants	34 participants n=8 Participants

PRIMARY outcome

Timeframe: Visit 12 (Week 36)

Population: This trial had an adaptive design that pre-specified the closure of the 32 U (units) (Group 5) in the event Acthar was not well tolerated at that dose. Based on tolerability, all patients initially included in the 32 U arm were combined with the 16 U arm (Group 3).

Percent change in eGFR at Visit 12 (Week 36) compared to average baseline eGFR obtained during screening

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Groups 2, 4, 6	Acthar 8 Units n=7 Participants Group 1	Acthar 16 Units n=16 Participants Groups 3, 5
Percent Change in Estimated Glomerular Filtration Rate (eGFR) at Visit 12	-24.927 percent change Standard Error 5.4198	-20.563 percent change Standard Error 6.8126	-17.447 percent change Standard Error 4.3473

SECONDARY outcome

Timeframe: Visit 17 (Week 52)

Population: This trial had an adaptive design that pre-specified the closure of the 32 U arm (Group 5) in the event Acthar was not well tolerated at that dose. Based on tolerability, all patients initially included in the 32 U arm were combined with the 16 U arm (Group 3).

Percent change in eGFR at Visit 17 (Week 52) compared to baseline eGFR obtained during screening

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Groups 2, 4, 6	Acthar 8 Units n=6 Participants Group 1	Acthar 16 Units n=10 Participants Groups 3, 5
Percent Change in eGFR at Visit 17	-20.407 percent change Standard Error 6.0183	-37.456 percent change Standard Error 7.8387	-22.097 percent change Standard Error 5.4619

SECONDARY outcome

Timeframe: Visit 12 (Week 36) and Visit 17 (Week 52)

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Groups 2, 4, 6	Acthar 8 Units n=7 Participants Group 1	Acthar 16 Units n=16 Participants Groups 3, 5
Frequency of Patients With a Doubling of Serum Creatinine, Progression to End-stage Renal Disease (ESRD), or Death Visit 17 (Week 52) · No	10 Participants	6 Participants	14 Participants
Frequency of Patients With a Doubling of Serum Creatinine, Progression to End-stage Renal Disease (ESRD), or Death Visit 12 (Week 36) · Yes	0 Participants	1 Participants	1 Participants
Frequency of Patients With a Doubling of Serum Creatinine, Progression to End-stage Renal Disease (ESRD), or Death Visit 12 (Week 36) · No	10 Participants	6 Participants	15 Participants
Frequency of Patients With a Doubling of Serum Creatinine, Progression to End-stage Renal Disease (ESRD), or Death Visit 17 (Week 52) · Yes	0 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Visit 12 (Week 36) and Visit 17 (Week 52)

Proportion of patients with complete remission (PCR 0.5 g/g) or partial remission (reduction in PCR of \>50% from baseline, plus PCR≤2.5 g/g but \>0.5 g/g) of proteinuria at Visit 12 (Week 36) and/or at Visit 17 (Week 52)

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Groups 2, 4, 6	Acthar 8 Units n=3 Participants Group 1	Acthar 16 Units n=8 Participants Groups 3, 5
Complete or Partial Remission of Proteinuria Visit 12 (Week 36) · Complete remission	0 Participants	0 Participants	1 Participants
Complete or Partial Remission of Proteinuria Visit 12 (Week 36) · Partial remission	1 Participants	0 Participants	0 Participants
Complete or Partial Remission of Proteinuria Visit 12 (Week 36) · No remission	8 Participants	3 Participants	7 Participants
Complete or Partial Remission of Proteinuria Visit 17 (Week 52) · Complete remission	0 Participants	0 Participants	1 Participants
Complete or Partial Remission of Proteinuria Visit 17 (Week 52) · Partial remission	0 Participants	0 Participants	0 Participants
Complete or Partial Remission of Proteinuria Visit 17 (Week 52) · No remission	6 Participants	2 Participants	7 Participants

SECONDARY outcome

Timeframe: Visit 12 (Week 36) and Visit 17 (Week 52)

Percent change in eGFR calculated using cystatin C compared to baseline obtained at Visit 2.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Groups 2, 4, 6	Acthar 8 Units n=3 Participants Group 1	Acthar 16 Units n=8 Participants Groups 3, 5
Percent Change in eGFR Calculated Using Cystatin C Visit 12 (Week 36)	-14.25 percent change Standard Deviation 17.155	-11.49 percent change Standard Deviation 10.334	-10.24 percent change Standard Deviation 22.066
Percent Change in eGFR Calculated Using Cystatin C Visit 17 (Week 52)	1.14 percent change Standard Deviation 21.155	-35.90 percent change Standard Deviation 1.509	-12.43 percent change Standard Deviation 20.522

SECONDARY outcome

Timeframe: Visit 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17

Percent change from baseline in eGFR by visit

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Groups 2, 4, 6	Acthar 8 Units n=7 Participants Group 1	Acthar 16 Units n=16 Participants Groups 3, 5
Percent Change From Baseline in eGFR by Visit Baseline to Visit 3	-6.19 percent change Standard Deviation 16.494	1.82 percent change Standard Deviation 11.347	0.86 percent change Standard Deviation 11.659
Percent Change From Baseline in eGFR by Visit Baseline to Visit 4	-11.76 percent change Standard Deviation 14.131	4.39 percent change Standard Deviation 9.133	-2.69 percent change Standard Deviation 11.252
Percent Change From Baseline in eGFR by Visit Baseline to Visit 5	-8.42 percent change Standard Deviation 14.942	-10.11 percent change Standard Deviation 9.614	-12.01 percent change Standard Deviation 14.395
Percent Change From Baseline in eGFR by Visit Baseline to Visit 6	-12.73 percent change Standard Deviation 8.881	-9.36 percent change Standard Deviation 14.723	-14.20 percent change Standard Deviation 16.300
Percent Change From Baseline in eGFR by Visit Baseline to Visit 7	-12.30 percent change Standard Deviation 6.888	-25.42 percent change Standard Deviation 10.079	-17.33 percent change Standard Deviation 21.629
Percent Change From Baseline in eGFR by Visit Baseline to Visit 8	-11.64 percent change Standard Deviation 6.539	-27.46 percent change Standard Deviation 11.435	-17.58 percent change Standard Deviation 23.071
Percent Change From Baseline in eGFR by Visit Baseline to Visit 9	-14.46 percent change Standard Deviation 8.535	-21.04 percent change Standard Deviation 8.414	-23.25 percent change Standard Deviation 18.344
Percent Change From Baseline in eGFR by Visit Baseline to Visit 10	-15.75 percent change Standard Deviation 10.914	-28.73 percent change Standard Deviation 6.789	-20.57 percent change Standard Deviation 23.747
Percent Change From Baseline in eGFR by Visit Baseline to Visit 11	-14.71 percent change Standard Deviation 12.052	-26.13 percent change Standard Deviation 3.041	-19.05 percent change Standard Deviation 20.996
Percent Change From Baseline in eGFR by Visit Baseline to Visit 12	-26.09 percent change Standard Deviation 11.687	-23.54 percent change Standard Deviation 7.853	-18.32 percent change Standard Deviation 22.929
Percent Change From Baseline in eGFR by Visit Baseline to Week 36 Endpoint	-24.96 percent change Standard Deviation 11.581	-20.27 percent change Standard Deviation 15.818	-17.55 percent change Standard Deviation 19.655
Percent Change From Baseline in eGFR by Visit Baseline to Visit 13	-17.94 percent change Standard Deviation 14.297	-29.37 percent change Standard Deviation 10.193	-23.46 percent change Standard Deviation 25.490
Percent Change From Baseline in eGFR by Visit Baseline to Visit 14	-21.88 percent change Standard Deviation 11.695	-33.99 percent change Standard Deviation 20.993	-29.96 percent change Standard Deviation 18.970
Percent Change From Baseline in eGFR by Visit Baseline to Visit 15	-17.40 percent change Standard Deviation 14.334	-38.05 percent change Standard Deviation 8.677	-19.95 percent change Standard Deviation 18.899
Percent Change From Baseline in eGFR by Visit Baseline to Visit 16	-19.16 percent change Standard Deviation 18.686	-40.18 percent change Standard Deviation 5.668	-27.33 percent change Standard Deviation 16.709
Percent Change From Baseline in eGFR by Visit Baseline to Visit 17	-18.43 percent change Standard Deviation 12.893	-42.70 percent change Standard Deviation 15.255	-24.55 percent change Standard Deviation 22.322
Percent Change From Baseline in eGFR by Visit Baseline to Week 52 Endpoint	-20.69 percent change Standard Deviation 12.433	-36.50 percent change Standard Deviation 11.573	-22.44 percent change Standard Deviation 20.669

SECONDARY outcome

Timeframe: Visits 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17

Percent change from baseline in PCR

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Groups 2, 4, 6	Acthar 8 Units n=7 Participants Group 1	Acthar 16 Units n=16 Participants Groups 3, 5
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 4	0.3837 percent change Standard Error 31.26202	44.7508 percent change Standard Error 78.75623	32.5701 percent change Standard Error 71.34201
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 5	-13.6630 percent change Standard Error 25.57771	47.4429 percent change Standard Error 54.03221	2.0594 percent change Standard Error 59.12062
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 6	-8.3326 percent change Standard Error 36.44142	72.1740 percent change Standard Error 85.20350	-1.6086 percent change Standard Error 47.69994
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 7	2.4621 percent change Standard Error 43.42213	55.9950 percent change Standard Error 42.92855	-10.6879 percent change Standard Error 50.13402
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 8	12.6601 percent change Standard Error 51.03925	53.2134 percent change Standard Error 43.68087	-8.5381 percent change Standard Error 65.06657
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 9	27.1483 percent change Standard Error 60.72960	82.7319 percent change Standard Error 67.83831	3.6409 percent change Standard Error 54.51979
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 10	8.2594 percent change Standard Error 45.36335	18.9898 percent change	-6.7500 percent change Standard Error 64.47765
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 11	15.1205 percent change Standard Error 92.21718	69.8646 percent change Standard Error 63.88789	0.4566 percent change Standard Error 71.78576
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 12	21.3540 percent change Standard Error 98.45289	59.8357 percent change Standard Error 55.64981	14.4619 percent change Standard Error 66.58000
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Week 36 Endpoint	19.1847 percent change Standard Error 93.07542	34.8848 percent change Standard Error 25.06961	50.2732 percent change Standard Error 85.87435
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 14	1.1894 percent change Standard Error 44.40008	11.7663 percent change Standard Error 5.63288	-16.4956 percent change Standard Error 52.71778
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 15	0.6294 percent change Standard Error 34.89553	4.3807 percent change Standard Error 6.70067	0.0091 percent change Standard Error 81.37129
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 16	0.0025 percent change Standard Error 47.25812	21.7536 percent change	3.6555 percent change Standard Error 74.40718
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Visit 17	20.8644 percent change Standard Error 88.18113	19.1625 percent change Standard Error 40.46023	-6.2356 percent change Standard Error 72.81798
Percent Change From Baseline in Protein to Creatinine Ratio (PCR) Baseline to Week 52 Endpoint	32.9735 percent change Standard Error 78.62621	66.7698 percent change Standard Error 84.63637	12.1049 percent change Standard Error 87.56153

SECONDARY outcome

Timeframe: Visit 12 (Week 36) and Visit 17 (Week 52)

Proportion of subjects whose best response was complete remission (PCR 0.5 g/g) or partial remission (reduction in PCR of \>50% from baseline, plus PCR≤2.5 g/g but \>0.5 g/g) of proteinuria

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Groups 2, 4, 6	Acthar 8 Units n=7 Participants Group 1	Acthar 16 Units n=16 Participants Groups 3, 5
Proportion of Subjects Whose Best Response Was Complete or Partial Remission of Proteinuria Week 36 · Complete remission	0 Participants	0 Participants	1 Participants
Proportion of Subjects Whose Best Response Was Complete or Partial Remission of Proteinuria Week 36 · Partial remission	1 Participants	0 Participants	3 Participants
Proportion of Subjects Whose Best Response Was Complete or Partial Remission of Proteinuria Week 36 · No remission	9 Participants	7 Participants	12 Participants
Proportion of Subjects Whose Best Response Was Complete or Partial Remission of Proteinuria Between Week 36 and Week 52 · Complete remission	0 Participants	0 Participants	1 Participants
Proportion of Subjects Whose Best Response Was Complete or Partial Remission of Proteinuria Between Week 36 and Week 52 · Partial remission	0 Participants	0 Participants	2 Participants
Proportion of Subjects Whose Best Response Was Complete or Partial Remission of Proteinuria Between Week 36 and Week 52 · No remission	8 Participants	2 Participants	5 Participants

SECONDARY outcome

Timeframe: Visit 6, 9, 12, and 17

Percent change from baseline of serum total cholesterol, triglycerides, LDL, HDL, Lp(a), albumin, and cortisol

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Groups 2, 4, 6	Acthar 8 Units n=7 Participants Group 1	Acthar 16 Units n=16 Participants Groups 3, 5
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Total cholesterol - Baseline to Visit 6	-7.2 percent change Standard Deviation 8.15	34.1 percent change Standard Deviation 23.94	10.1 percent change Standard Deviation 29.82
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Total cholesterol - Baseline to Visit 9	13.9 percent change Standard Deviation 22.90	20.3 percent change Standard Deviation 27.82	14.2 percent change Standard Deviation 25.95
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Total cholesterol - Baseline to Visit 12	3.4 percent change Standard Deviation 22.97	11.1 percent change Standard Deviation 24.57	11.1 percent change Standard Deviation 32.58
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Total cholesterol - Baseline to Week 36 Endpoint	3.9 percent change Standard Deviation 21.74	26.4 percent change Standard Deviation 28.05	12.9 percent change Standard Deviation 24.22
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Total cholesterol - Baseline to Visit 17	6.3 percent change Standard Deviation 20.82	-12.1 percent change Standard Deviation 1.57	9.6 percent change Standard Deviation 33.08
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Total cholesterol - Baseline to Week 52 Endpoint	6.3 percent change Standard Deviation 20.82	26.8 percent change Standard Deviation 45.79	9.4 percent change Standard Deviation 30.28
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Triglycerides - Baseline to Visit 6	1.6 percent change Standard Deviation 32.24	30.0 percent change Standard Deviation 34.97	20.5 percent change Standard Deviation 58.06
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Triglycerides - Baseline to Visit 9	18.4 percent change Standard Deviation 34.74	7.9 percent change Standard Deviation 36.59	31.0 percent change Standard Deviation 65.70
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Triglycerides - Baseline to Visit 12	8.3 percent change Standard Deviation 40.39	-7.1 percent change Standard Deviation 25.12	29.2 percent change Standard Deviation 61.09
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Triglycerides - Baseline to Week 36 Endpoint	8.9 percent change Standard Deviation 38.12	48.8 percent change Standard Deviation 141.71	19.9 percent change Standard Deviation 38.54
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Triglycerides - Baseline to Visit 17	22.6 percent change Standard Deviation 62.47	-37.4 percent change Standard Deviation 18.78	27.7 percent change Standard Deviation 63.00
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Triglycerides - Baseline to Week 52 Endpoint	22.6 percent change Standard Deviation 62.47	33.5 percent change Standard Deviation 76.59	18.2 percent change Standard Deviation 59.15
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol LDL-C - Baseline to Visit 6	-4.8 percent change Standard Deviation 28.04	47.4 percent change Standard Deviation 35.40	8.1 percent change Standard Deviation 42.39
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol LDL-C - Baseline to Visit 9	16.9 percent change Standard Deviation 33.30	36.1 percent change Standard Deviation 50.37	24.5 percent change Standard Deviation 48.65
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol LDL-C - Baseline to Visit 12	16.0 percent change Standard Deviation 45.78	23.2 percent change Standard Deviation 45.40	26.4 percent change Standard Deviation 74.60
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol LDL-C - Baseline to Week 36 Endpoint	15.9 percent change Standard Deviation 43.16	42.0 percent change Standard Deviation 48.66	12.4 percent change Standard Deviation 54.63
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol LDL-C - Baseline to Visit 17	7.4 percent change Standard Deviation 23.12	-9.9 percent change Standard Deviation 12.73	25.9 percent change Standard Deviation 86.13
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol LDL-C - Baseline to Week 52 Endpoint	7.4 percent change Standard Deviation 23.12	43.2 percent change Standard Deviation 66.57	24.1 percent change Standard Deviation 76.69
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol HDL-C - Baseline to Visit 6	-3.2 percent change Standard Deviation 14.03	11.8 percent change Standard Deviation 8.94	18.1 percent change Standard Deviation 35.97
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol HDL-C - Baseline to Visit 9	0.0 percent change Standard Deviation 11.52	9.8 percent change Standard Deviation 4.12	3.4 percent change Standard Deviation 11.34
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol HDL-C - Baseline to Visit 12	3.7 percent change Standard Deviation 26.98	11.4 percent change Standard Deviation 2.70	-6.9 percent change Standard Deviation 13.21
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol HDL-C - Baseline to Week 36 Endpoint	2.8 percent change Standard Deviation 25.59	6.7 percent change Standard Deviation 7.83	19.0 percent change Standard Deviation 58.40
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol HDL-C - Baseline to Visit 17	-5.0 percent change Standard Deviation 7.15	3.0 percent change Standard Deviation 12.26	-9.2 percent change Standard Deviation 15.91
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol HDL-C - Baseline to Week 52 Endpoint	-5.0 percent change Standard Deviation 7.15	-0.2 percent change Standard Deviation 17.50	-3.2 percent change Standard Deviation 21.37
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Lp(a) - Baseline to Visit 6	-7.2 percent change Standard Deviation 14.30	35.9 percent change Standard Deviation 95.42	22.7 percent change Standard Deviation 41.97
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Lp(a) - Baseline to Visit 9	1.9 percent change Standard Deviation 20.24	1.2 percent change Standard Deviation 9.32	28.0 percent change Standard Deviation 67.60
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Lp(a) - Baseline to Visit 12	6.1 percent change Standard Deviation 31.56	23.3 percent change Standard Deviation 20.74	10.7 percent change Standard Deviation 41.39
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Lp(a) - Baseline to Week 36 Endpoint	7.5 percent change Standard Deviation 30.07	49.2 percent change Standard Deviation 85.05	16.9 percent change Standard Deviation 48.51
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Lp(a) - Baseline to Visit 17	28.5 percent change Standard Deviation 57.71	19.9 percent change Standard Deviation 24.25	21.7 percent change Standard Deviation 65.09
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Lp(a) - Baseline to Week 52 Endpoint	28.5 percent change Standard Deviation 57.71	55.6 percent change Standard Deviation 85.65	21.2 percent change Standard Deviation 58.11
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Serum albumin - Baseline to Visit 6	-1.92 percent change Standard Deviation 4.848	-9.79 percent change Standard Deviation 7.256	-3.78 percent change Standard Deviation 9.721
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Serum albumin - Baseline to Visit 9	-2.49 percent change Standard Deviation 6.685	-7.77 percent change Standard Deviation 8.638	-3.75 percent change Standard Deviation 10.749
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Serum albumin - Baseline to Visit 12	-0.89 percent change Standard Deviation 6.798	-2.67 percent change Standard Deviation 14.597	-4.09 percent change Standard Deviation 4.507
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Serum albumin - Baseline to Week 36 Endpoint	-1.42 percent change Standard Deviation 6.629	-5.96 percent change Standard Deviation 10.357	-7.23 percent change Standard Deviation 6.083
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Serum albumin - Baseline to Visit 17	-0.22 percent change Standard Deviation 9.002	8.06 percent change Standard Deviation 15.119	-2.33 percent change Standard Deviation 5.898
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Serum albumin - Baseline to Week 52 Endpoint	-1.77 percent change Standard Deviation 8.822	-6.15 percent change Standard Deviation 14.379	-2.75 percent change Standard Deviation 6.207
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Cortisol - Baseline to Visit 6	-5.86 percent change Standard Deviation 28.676	45.08 percent change Standard Deviation 151.882	180.70 percent change Standard Deviation 237.206
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Cortisol - Baseline to Visit 9	-11.23 percent change Standard Deviation 22.791	14.44 percent change Standard Deviation 26.399	50.08 percent change Standard Deviation 135.687
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Cortisol - Baseline to Visit 12	-9.44 percent change Standard Deviation 39.280	17.72 percent change Standard Deviation 35.704	52.77 percent change Standard Deviation 97.269
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Cortisol - Baseline to Week 36 Endpoint	-8.36 percent change Standard Deviation 37.189	63.46 percent change Standard Deviation 125.208	64.32 percent change Standard Deviation 187.125
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Cortisol - Baseline to Visit 17	-13.11 percent change Standard Deviation 31.825	84.26 percent change Standard Deviation 88.861	7.09 percent change Standard Deviation 24.739
Percent Change From Baseline of Serum Total Cholesterol, Triglycerides, LDL, HDL, Lp(a), Albumin, and Cortisol Cortisol - Baseline to Week 52 Endpoint	-8.53 percent change Standard Deviation 28.727	51.82 percent change Standard Deviation 91.328	30.21 percent change Standard Deviation 89.880

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 36

Change from baseline mean HbA1c (%) to Week 36

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Groups 2, 4, 6	Acthar 8 Units n=3 Participants Group 1	Acthar 16 Units n=8 Participants Groups 3, 5
Change in Mean HbA1c	-0.22 %HbA1c Standard Deviation 0.694	-0.33 %HbA1c Standard Deviation 1.429	-0.25 %HbA1c Standard Deviation 0.729

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Acthar 8 Units

Serious events: 1 serious events

Other events: 6 other events

Deaths: 1 deaths

Acthar 16 Units

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Overall

Serious events: 5 serious events

Other events: 30 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=10 participants at risk Groups 2, 4, 6	Acthar 8 Units n=7 participants at risk Group 1	Acthar 16 Units n=17 participants at risk Groups 3, 5; This trial had an adaptive design that pre-specified the closure of the 32 U arm (Group 5) in the event Acthar was not well tolerated at that dose. Based on tolerability, all patients initially included in the 32 U arm were combined with the 16 U arm (Group 3). Thus, Adverse Events were not collected separately for these Arms.	Overall n=34 participants at risk Groups 1, 2, 3, 4, 5, 6
Gastrointestinal disorders Gastric antral vascular ectasia	10.0% 1/10 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/7 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/17 • Adverse event data displayed was collected during the 36 week treatment period.	2.9% 1/34 • Adverse event data displayed was collected during the 36 week treatment period.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	10.0% 1/10 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/7 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/17 • Adverse event data displayed was collected during the 36 week treatment period.	2.9% 1/34 • Adverse event data displayed was collected during the 36 week treatment period.
Gastrointestinal disorders Duodenitis	0.00% 0/10 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/7 • Adverse event data displayed was collected during the 36 week treatment period.	5.9% 1/17 • Adverse event data displayed was collected during the 36 week treatment period.	2.9% 1/34 • Adverse event data displayed was collected during the 36 week treatment period.
Cardiac disorders Acute myocardial infarction	0.00% 0/10 • Adverse event data displayed was collected during the 36 week treatment period.	14.3% 1/7 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/17 • Adverse event data displayed was collected during the 36 week treatment period.	2.9% 1/34 • Adverse event data displayed was collected during the 36 week treatment period.
Cardiac disorders Cardiac failure congestive	0.00% 0/10 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/7 • Adverse event data displayed was collected during the 36 week treatment period.	5.9% 1/17 • Adverse event data displayed was collected during the 36 week treatment period.	2.9% 1/34 • Adverse event data displayed was collected during the 36 week treatment period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 1/10 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/7 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/17 • Adverse event data displayed was collected during the 36 week treatment period.	2.9% 1/34 • Adverse event data displayed was collected during the 36 week treatment period.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/10 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/7 • Adverse event data displayed was collected during the 36 week treatment period.	5.9% 1/17 • Adverse event data displayed was collected during the 36 week treatment period.	2.9% 1/34 • Adverse event data displayed was collected during the 36 week treatment period.
Renal and urinary disorders Acute kidney injury	0.00% 0/10 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/7 • Adverse event data displayed was collected during the 36 week treatment period.	5.9% 1/17 • Adverse event data displayed was collected during the 36 week treatment period.	2.9% 1/34 • Adverse event data displayed was collected during the 36 week treatment period.
Vascular disorders Deep vein thrombosis	0.00% 0/10 • Adverse event data displayed was collected during the 36 week treatment period.	0.00% 0/7 • Adverse event data displayed was collected during the 36 week treatment period.	5.9% 1/17 • Adverse event data displayed was collected during the 36 week treatment period.	2.9% 1/34 • Adverse event data displayed was collected during the 36 week treatment period.

Other adverse events

Additional Information

Medical Information Call Center

Mallinckrodt

Phone: 800-556-3314

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A sole participant institution shall not, without Sponsor's prior written consent, independently publish or otherwise disclose any results of this multicenter study prior to a "multicenter" publication, or 12 months after completion of the study, whichever occurs first. Institution and Principal Investigator shall have the right to publish and present the results of Institution's and Principal Investigator's activities solely in accordance with the Sponsor's written provisions.
Publication restrictions are in place

Restriction type: OTHER