ACTHAR Gel for Drug REsistant Nephrotic Syndrome in Children

Steroid-Resistant Nephrotic Syndrome Clinical Trial

— ADRENL  

Official title:

ADRENL - ACTHAR Gel for Drug REsistant Nephrotic Syndrome in Children, Pilot Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03408405
• Other study ID #: 1050945-5
• Status: Withdrawn
• Phase: Phase 4
• Start date: June 2018
• Est. completion date: July 2021

Study information

• Verified date: April 2019
• Source: Rhode Island Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We propose to study the use of purified porcine Acthar Gel (ACTHAR, Mallinckrodt Pharmaceuticals) for treatment of steroid resistance nephrotic syndrome (SRNS) in a prospective pilot study. We plan to enroll 25 children between the ages of 2 to 21 years. Children fulfilling strict inclusion criteria, whose parents agree to written informed consent after institutional IRB approval for the study, will be enrolled. Purified porcine Acthar Gel will be administered SQ to all children using a defined treatment protocol for a period of six months. Renal function, urine protein excretion, serum albumin levels, blood pressure and growth parameters will be monitored closely on all patients. Baseline urine protein excretion will be compared to end of treatment levels to determine successful response to therapy. There will be an 18 month enrollment period, 6 month treatment period and a 12 month follow-up period.

Description:

Treatment Protocol:

Patients who fulfill inclusion criteria and who agree to participate after signing informed consent and assent forms will be treated with the following protocol:

Acthar Gel will be dosed by body surface area (BSA) using the Dubois Method. The dose of Acthar Gel will be 80 units/1.73 m2 per dose administered subcutaneously (SQ) twice a week on Mondays and Thursdays.

Week 1 to 2:

During week 1, patients will receive 50% of initial calculated dose twice a week.

During week 2, patients will receive 75% of initial calculated dose twice a week.

Week 3 to 6 Months:

Patients will receive the full dose of Acthar Gel (80 units/1.73 m2 per dose) administered subcutaneously (SQ) twice a week on Mondays and Thursdays.

During this period, the treating physician will have the discretion of reducing the dose of Acthar Gel by 25-50% based on response with respect to reduction in proteinuria and tolerability of side-effects (uncontrolled hypertension, excessive weight gain, severe acne, hyperglycemia, etc.)

Patients will have the option of remaining on Acthar Gel after the 6 month study period based on clinical response at discretion of the co-PI. Study drug will be provided free of cost to patients in the first 6 months only.

Concomitant Treatments:

1. Amlodipine 0.1 mg/kg PO in one or two divided doses will be given to all patients who develop elevated blood pressure (>95th percentile) starting after 14 days of initiation of Acthar Gel therapy and will continue till 6 months. Dose can be increased up to 0.5 mg/kg divided bid as needed to achieve goal BP <95th percentile. If Amlodipine is not covered by the participants insurance, then an alternate calcium channel blocker will be started at the clinical discretion of the PI/co-PI that is covered by insurance. If the participant is not covered by any insurance the participant will have to pay out of pocket

2. If BP remains elevated despite maximum calcium channel therapy as described in the study protocol above, the choice and dose of additional anti-hypertensive agents will be at the discretion of the study investigator on an individualized and as needed basis.

3. Patients on prednisone on initiation of study will be tapered off over 2-4 weeks. Non-steroidal immunosuppression may be tapered off over four weeks after the start of Acthar Gel therapy at the discretion of the PI/Co-PI.

4. Additional standard of care therapy (statins, vitamin D, antacids, etc.) can be continued and modified based on the discretion and clinical judgment of the study PI/Co-PIs.

Quality of Life Assessment:

Quality of life will be measured using the patient and parent self-report versions of the Pediatric Quality of Life Inventory, ESRD, Acute Version. The PedsQL 3.0 ESRD Scales measure physical, emotional, social and role (i.e. school) dimensions. Scores are derived for physical functioning and psychological functioning, in addition to a total score, which enables comparison against healthy populations. Scales are rated on a 5-point Likert scale (0 = never, 1= almost never, 2 = sometimes, 3 = often, 4 = almost always), with scores linearly transformed to range from 0 - 100, with higher scores indicating fewer problems or symptoms.

Surveys will be administered by trained study personnel at enrollment (baseline), six months, 12 months, and 18 months.

Laboratory Testing:

Baseline and then once a month till the end of the treatment period (6 months): Serum electrolytes, BUN, creatinine, albumin, ACTH level, glucose, random cortisol, calcium, magnesium, phosphorus, ALT, AST, total and direct bilirubin, fasting cholesterol, triglycerides, HDL, LDL, urine protein to creatinine ratio. During the 12 month follow-up period laboratory evaluation will be performed every third month. (11 total blood draws). A urine pregnancy test shall be sent on all female patients of child-bearing potential at the beginning and end of treatment period.

All available biopsy slides will be reviewed by a blinded renal pathologist to insure accuracy and to confirm the initial histologic diagnosis.

Telephone Contact One, two and three weeks after initial dose. Phone contacts will screen for: adverse events, and review dosing of ACTHAR GEL.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2021
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 21 Years

Eligibility

Inclusion Criteria:

1. Patients between the ages of 2-21 years who fail a minimum of 12 weeks of cumulative therapy with prednisone OR one other alternate immunosuppressive agent for treatment of nephrotic syndrome, will be eligible for inclusion. Nephrotic syndrome is defined as: Presence of edema, Edema, UP/C =2, =300mg/dl or 3+ protein on Albustix, and hypoalbuminemia =2.5 g/dL

2. Calculated GFR (eGFR) using modified Schwartz formula of > 50 mls/min/m2. (Modified Schwartz formula = 0.413 x height (cms) ÷ serum creatinine mg/dL)

3. A clinical or biopsy diagnosis of nephrotic syndrome within the last 3 years prior to enrollment in the study.

4. Renal biopsy (if available) consistent with a diagnosis of Minimal Change Disease, IgM nephropathy, Mesangioproliferative Glomerulonephritis, Primary Focal Segmental Glomerulosclerosis or C1q Nephropathy

Exclusion Criteria:

1. Patients with an inherited or genetic disorder presenting with nephrotic syndrome (eg:

NPHS 1 & 2 defects, WT-1 mutations, a actinin 4 mutation, TRP-6 mutation).

2. Presence of diabetes or severe (stage 2) uncontrolled hypertension.

3. Any metabolic condition that specifically precludes the use of Acthar Gel for treatment.

4. Pregnancy or unwilling to agree to contraception which may include abstinence.

5. eGFR <50 mls/min/m2

Related Conditions & MeSH terms

• Nephrosis
• Nephrotic Syndrome
• Steroid-Resistant Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• Acthar Gel 80 UNT/ML Injectable Solution
Participant will self inject 'Acthar Gel 80 UNT/ML Injectable Solution' 2 x per week for six months.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Rhode Island Hospital	Mallinckrodt, Medalytics, University of Minnesota, MN

References & Publications (8)

Berg AL, Arnadottir M. ACTH-induced improvement in the nephrotic syndrome in patients with a variety of diagnoses. Nephrol Dial Transplant. 2004 May;19(5):1305-7. — View Citation

Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012;36(1):58-67. doi: 10.1159/000339287. Epub 2012 Jun 19. — View Citation

Bomback AS, Tumlin JA, Baranski J, Bourdeau JE, Besarab A, Appel AS, Radhakrishnan J, Appel GB. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011 Mar 14;5:147-53. doi: 10.2147/DDDT.S17521. — View Citation

Coppo R. Non-steroidal and non-cytotoxic therapies for nephrotic syndrome. Nephrol Dial Transplant. 2008 Jun;23(6):1793-6. doi: 10.1093/ndt/gfn211. Epub 2008 Apr 25. — View Citation

LAUSON HD, FORMAN CW, McNAMARA H, MATTAR G, BARNETT HL. The effect of corticotropin (ACTH) on glomerular permeability to albumin in children with the nephrotic syndrome. J Clin Invest. 1954 Apr;33(4):657-64. — View Citation

Mackay MT, Weiss SK, Adams-Webber T, Ashwal S, Stephens D, Ballaban-Gill K, Baram TZ, Duchowny M, Hirtz D, Pellock JM, Shields WD, Shinnar S, Wyllie E, Snead OC 3rd; American Academy of Neurology; Child Neurology Society. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. 2004 May 25;62(10):1668-81. Review. — View Citation

Ponticelli C, Passerini P, Salvadori M, Manno C, Viola BF, Pasquali S, Mandolfo S, Messa P. A randomized pilot trial comparing methylprednisolone plus a cytotoxic agent versus synthetic adrenocorticotropic hormone in idiopathic membranous nephropathy. Am J Kidney Dis. 2006 Feb;47(2):233-40. — View Citation

Rauen T, Michaelis A, Floege J, Mertens PR. Case series of idiopathic membranous nephropathy with long-term beneficial effects of ACTH peptide 1-24. Clin Nephrol. 2009 Jun;71(6):637-42. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Remission of proteinuria	Partial remission: Greater than or equal to 50% reduction in proteinuria when compared to baseline.; Complete remission: Greater than or equal to 90% reduction in proteinuria when compared to baseline or Urine Protein Creatinine ratio less than 0.5.	18 months
Secondary	Blood pressure	Blood pressure during study visit as measured in mm/Hg	18 months
Secondary	Serum Creatinine	Serum value in mg/dL	18 months
Secondary	BMI	Weight (kgs) and height (cms) will be combined to report BMI in kg/m^2	18 months
Secondary	Serum Glucose	Serum value in mg/dL	18 months
Secondary	Serum Lipids	Serum Value in mg/dL	18 months
Secondary	Quality of life measures obtained via survey	PedsQL 3.0 will be used as the standardized survey tool	18 months