ACTHAR Gel for Drug REsistant Nephrotic Syndrome in Children

NCT03408405 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: 1050945-5
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Steroid-Resistant Nephrotic Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Blood pressure

  18 months

• Serum Creatinine

  18 months

• BMI

  18 months

• Serum Glucose

  18 months

• Serum Lipids

  18 months

Study Arms (1)

Acthar Gel treatment group

EXPERIMENTAL

Participants will be treated with 'Acthar Gel 80 UNT/ML Injectable Solution'. Initial dose for week 1 will be 50% of 80 units, injected twice per week. Week 2 is 75% of 80 units, week 3 and throughout treatment period (6 months in total) will be 80 units/ml twice per week.

Drug: Acthar Gel 80 UNT/ML Injectable Solution

Interventions

Acthar Gel 80 UNT/ML Injectable Solution DRUG

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

Also known as: H.P. Acthar gel

Acthar Gel treatment group

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Calculated GFR (eGFR) using modified Schwartz formula of \> 50 mls/min/m2. (Modified Schwartz formula = 0.413 x height (cms) ÷ serum creatinine mg/dL)
• A clinical or biopsy diagnosis of nephrotic syndrome within the last 3 years prior to enrollment in the study.
• Renal biopsy (if available) consistent with a diagnosis of Minimal Change Disease, IgM nephropathy, Mesangioproliferative Glomerulonephritis, Primary Focal Segmental Glomerulosclerosis or C1q Nephropathy

You may not qualify if:

• Patients with an inherited or genetic disorder presenting with nephrotic syndrome (eg: NPHS 1 \& 2 defects, WT-1 mutations, α actinin 4 mutation, TRP-6 mutation).
• Presence of diabetes or severe (stage 2) uncontrolled hypertension.
• Any metabolic condition that specifically precludes the use of Acthar Gel for treatment.
• Pregnancy or unwilling to agree to contraception which may include abstinence.
• eGFR \<50 mls/min/m2

Sponsors & Collaborators

• Rhode Island Hospital: lead
• Mallinckrodt: collaborator
• University of Minnesota: collaborator
• Medalytics: collaborator

Related Publications (8)

• 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. No abstract available.

  PMID: 18441003 BACKGROUND

• 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. doi: 10.1212/01.wnl.0000127773.72699.c8.

  PMID: 15159460 BACKGROUND

• 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. doi: 10.5414/cnp71637.

  PMID: 19473632 BACKGROUND

• 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. doi: 10.1053/j.ajkd.2005.10.016.

  PMID: 16431252 BACKGROUND

• 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. doi: 10.1093/ndt/gfh110. No abstract available.

  PMID: 15102969 BACKGROUND

• 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.

  PMID: 21448451 BACKGROUND

• 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.

  PMID: 22722778 BACKGROUND

• 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. doi: 10.1172/JCI102936. No abstract available.

  PMID: 13152205 BACKGROUND

MeSH Terms

Conditions

Nephrotic Syndrome

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Mohammed K Faizan, MD

  Rhode Island Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: January 24, 2018
• Study Start: June 1, 2018
• Primary Completion: January 1, 2021
• Study Completion: July 1, 2021
• Last Updated: April 23, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share