Study of Adrenocorticotropic Hormone on Children With Frequent Relapse or Steroid-dependent Nephrotic Syndrome: a Prospective, Multicenter, Randomized，Open-label Clinical Trial.

NCT06079788 | Recruiting Phase 3

• 1 other identifier: STAIR
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 8

Brief Summary

Primary nephrotic syndrome accounts for approximately 90% of the total number of nephrotic syndrome in childhood and it is the most common glomerular disease in children. Although treatment with steroids is useful for primary nephrotic syndrome, proving to cause frequent relapse/steroid-dependent nephrotic syndrome after treatment and the usage of immunosuppressive agents has become a new choice for the treatment of such patients. This study is a prospective, multicenter, randomized，open-label clinical trial, evaluating the efficacy and safety of steroid combined with adrenocorticotrophic hormone（ACTH） to children who with frequently relapsing or steroid-dependent nephrotic syndrome, all we wish to obtain the proper drug choice and individualized treatment options for children with nephrotic syndrome.

Conditions

Nephrotic Syndrome in Children

Keywords

Nephrotic Syndrome; Frequently Relapsing Nephrotic Syndrome; Steroid Dependent Nephrotic Syndrome; Adrenocorticotropic Hormone

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival time(day) within 48 weeks

  Recurrence-free survival time(day) within 48 weeks

  Within 48 weeks after randomization

Secondary Outcomes (8)

• Number of relapses during 48 weeks follow up

  Within 48 weeks after randomization

• The first time to relapse

  Within 48 weeks after randomization

• Cumulative prednisone dosage (milligrams per kilogram per year)

  Within 48 weeks after randomization

• Change in renal function of the patients

  Within 48 weeks after randomization

• Change in anthropometry and growth velocity during 48 weeks after randomization

  Within 48 weeks after randomization

Study Arms (2)

Adrenocorticotrophic Hormone Group

EXPERIMENTAL

ACTH 2 IU/kg/ day, qd,（the maximum dose ≤ 50 IU）, 28 days of continuous use for 5 days， for 24 weeks. Prednisone: 5mg；Oral tablets; 1.5-2 mg/kg, qod or 0.75-1mg/kg/day,qd

Drug: Adrenocorticotrophic Hormone

Steroid Group

ACTIVE COMPARATOR

Prednisone: 5mg；Oral tablets; 1.5-2 mg/kg, qod or 0.75-1mg/kg/day,qd, then gradually taper the steroid by 0.25mg/kg （qod） or 0.125mg/kg （qd） every 4 weeks.

Drug: Steroid

Interventions

Adrenocorticotrophic Hormone DRUG

For patients in complete remission, ACTH is given at a prednisone dose of 1.5-2mg/kg qod or 0.75-1mg/kg qd. ACTH 2 IU/kg/ day, qd,（the maximum dose ≤ 50 IU）, 28 days of continuous use for 5 days， for 24 weeks. Prednisone: 5mg；Oral tablets; 1.5-2 mg/kg, qod or 0.75-1mg/kg/day,qd, then gradually taper the steroid by 0.25mg/kg qod or 0.125mg/kg qd every 4 weeks.If stable, taper to 5mg qod (body surface area \> 1.0m2) and 2.5mg qod (body surface area \< 1.0m2) and maintain the dose until study completion.

Also known as: ACTH

Adrenocorticotrophic Hormone Group

Steroid DRUG

For patients in complete remission, Prednisone: 5mg；Oral tablets; 1.5-2 mg/kg, qod or 0.75-1mg/kg/day,qd, then gradually taper the steroid by 0.25mg/kg qod or 0.125mg/kg qd every 4 weeks. If stable, taper to 5mg qod (body surface area \> 1.0m2) and 2.5mg qod (body surface area \< 1.0m2) and maintain the dose until study completion.

Steroid Group

Eligibility Criteria

• Age: 2 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 2-14 years old;
• Sensitive but frequent relapses or steroids dependence nephrotic syndrome
• No severe hormonal side effects and/or low-dose steroids dependent idiopathic nephrotic syndrome in children (defined as two relapses with an average dose \< 0.5mg/kg/day or equivalent alternate-day dose)
• Normal renal function: eGFR≥90ml/min/1.73m2;
• Morning urine protein \<1+ or urine protein-creatinine ratio \<0.2g/g (\<20 mg/mmol) for 3 consecutive days and above when in enroll;
• Prednisone dose was 1.5-2 mg/kg per day before admission;
• No use of other immunosuppressants (such as tacrolimus, mortecophenolate, cyclosporin A, cyclophosphamide, levamisole, imidazole ribin, or tripterygium, etc.) within 3 months, and no use of rituximab or beliumab within 6 months.

You may not qualify if:

• Family history of nephrotic syndrome, chronic glomerulonephritis, uremia and other kidney diseases;
• Patients with congenital or acquired immunodeficiency, or with active tuberculosis, active CMV, EBV, hepatitis B, hepatitis C, HIV infection, deep fungal infection, or other active infections;
• Recurrent or persistent hypertension;
• Secondary nephrotic syndrome, such as nephrotic syndrome secondary to systemic lupus erythematosus, diabetes, drug poisoning and infection;
• Combined with other kidney diseases, such as polycystic kidney, ANCA vasculitis, urinary system malformations, etc.;
• Patients with hypertension, diabetes, tuberculosis, suppurative or fungal infection, gastric and duodenal ulcer disease and heart failure; Patients with other serious heart, liver and other important organs, blood system, endocrine system and other system lesions;
• Co-occurrence of other monogenic genetic diseases known to affect the condition of nephrotic syndrome;
• Patients with serious autoimmune diseases or tumors;
• Use of other immunosuppressants (such as tacrolimus, mortecophenolate, cyclosporin A, cyclophosphamide, levamisole, imidazole ribin, or tripterygium, etc.) within 3 months, and no use of rituximab or beliumab within 6 months;
• Patients who are known to be allergic to ACTH, glucocorticoids, or any of the components of these drugs, and patients with severe hormone-related side effects
• History of organ transplantation (excluding corneal and hair transplantation);
• Patients who had participated in other clinical trials within three months prior to enrollment;

Sponsors & Collaborators

• Mao Jianhua: lead
• Tongji Hospital: collaborator
• Children's Hospital affiliated to Capital Institute of Pediatrics: collaborator
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Children's Hospital of Nanjing Medical University: collaborator
• Kunming Children's Hospital: collaborator
• Yuying Childrens Hospital of Wenzhou Medical University: collaborator
• Ningbo Women & Children's Hospital: collaborator

Study Sites (8)

Tongji Hospital

Wuhan, Hubei, 430030, China

RECRUITING

Nanjing Children's Hospital

Nanjing, Jiangsu, 210008, China

RECRUITING

Kunming Children's Hospital

Kunming, Yunnan, 650000, China

RECRUITING

Children's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

Ningbo Women & Children's Hospital

Ningbo, Zhejiang, 315000, China

RECRUITING

Yuying Childrens Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

RECRUITING

Children's Hospital affiliated to Capital Institute of Pediatrics

Beijing, 100000, China

RECRUITING

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, 200000, China

RECRUITING

Related Publications (8)

• Wang CS, Greenbaum LA. Nephrotic Syndrome. Pediatr Clin North Am. 2019 Feb;66(1):73-85. doi: 10.1016/j.pcl.2018.08.006.

  PMID: 30454752 BACKGROUND

• Wong W. Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance study. J Paediatr Child Health. 2007 May;43(5):337-41. doi: 10.1111/j.1440-1754.2007.01077.x.

  PMID: 17489822 BACKGROUND

• Chakraborty R, Mehta A, Nair N, Nemer L, Jain R, Joshi H, Raina R. ACTH Treatment for Management of Nephrotic Syndrome: A Systematic Review and Reappraisal. Int J Nephrol. 2020 Jun 4;2020:2597079. doi: 10.1155/2020/2597079. eCollection 2020.

  PMID: 32566293 BACKGROUND

• Lieberman KV, Pavlova-Wolf A. Adrenocorticotropic hormone therapy for the treatment of idiopathic nephrotic syndrome in children and young adults: a systematic review of early clinical studies with contemporary relevance. J Nephrol. 2017 Feb;30(1):35-44. doi: 10.1007/s40620-016-0308-3. Epub 2016 Apr 16.

  PMID: 27084801 BACKGROUND

• Hladunewich MA, Cattran D, Beck LH, Odutayo A, Sethi S, Ayalon R, Leung N, Reich H, Fervenza FC. A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar(R) Gel) in nephrotic syndrome due to idiopathic membranous nephropathy. Nephrol Dial Transplant. 2014 Aug;29(8):1570-7. doi: 10.1093/ndt/gfu069. Epub 2014 Apr 8.

  PMID: 24714414 BACKGROUND

• Hogan J, Bomback AS, Mehta K, Canetta PA, Rao MK, Appel GB, Radhakrishnan J, Lafayette RA. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clin J Am Soc Nephrol. 2013 Dec;8(12):2072-81. doi: 10.2215/CJN.02840313. Epub 2013 Sep 5.

  PMID: 24009220 BACKGROUND

• Zand L, Canetta P, Lafayette R, Aslam N, Jan N, Sethi S, Fervenza FC. An Open-Label Pilot Study of Adrenocorticotrophic Hormone in the Treatment of IgA Nephropathy at High Risk of Progression. Kidney Int Rep. 2019 Oct 31;5(1):58-65. doi: 10.1016/j.ekir.2019.10.007. eCollection 2020 Jan.

  PMID: 31922061 BACKGROUND

• Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.

  PMID: 39513526 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

Adrenocorticotropic Hormone; Steroids

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• yi Xie

  Recruiting

  STUDY DIRECTOR

Central Study Contacts

jianhua Mao, MD

CONTACT

0571-87061007; maojh88@126.com

yi Xie

CONTACT

ylfx27@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: October 8, 2023
• First Posted: October 12, 2023
• Study Start: November 1, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 12, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (8)