Study of NM8074 in Patients With Immunoglobulin A Nephropathy (IgAN)

Официальное название

A Phase II, Open-Label Study of NM8074 in Patients With Immunoglobulin A Nephropathy (IgAN)

Обзор

This is a Phase II, open-label study designed to To evaluate the safety and efficacy of NM8074 in reducing proteinuria relative to baseline in IgAN patients after 99 days of treatment.

Подробное описание

The proposed study, NM8074-IgAN-601, will enroll a planned total of 10 patients as subjects for the trial. All subjects will be administered 17 mg/kg of NM8074 intravenously every week, for a total of 15 doses from Day 1 to Day 99 of the Treatment Period.

Вмешательства

• Препарат NM8074
  NM8074 will be administered as an intravenous infusion. All subjects will be administered 17 mg/kg of NM8074 intravenously weekly for a total of 15 doses from Day 1 to Day 99 of the Treatment Period.

Первичные конечные точки

• Change from Baseline or Percent Change from Baseline in urine protein to creatinine concentration ratio [Срок оценки: Up to Study Day 99]

Вторичные конечные точки (12)

• Change from Baseline or Percent Change from Baseline in eGFR [Срок оценки: Up to Study Day 155]
• Change from Baseline or Percent Change from Baseline in Serum Creatinine [Срок оценки: Up to Study Day 155]
• Change from Baseline or Percent Change from Baseline in Hematuria [Срок оценки: Up to Study Day 155]
• Change from Baseline or Percent Change from Baseline in Urine Albumin to Creatinine concentration ratio [Срок оценки: Up to Study Day 155]
• Change from Baseline or Percent Change from Baseline in Bb plasma levels [Срок оценки: Up to Study Day 155]
• Change from Baseline or Percent Change from Baseline in sC5b-9 plasma levels [Срок оценки: Up to Study Day 155]
• Change from Baseline or Percent Change from Baseline in UPCR [Срок оценки: Up to Study Day 155]
• Change from Baseline or Percent Change from Baseline in Tmax [Срок оценки: Up to Study Day 155]
• Change from Baseline or Percent Change from Baseline in Cmax [Срок оценки: Up to study Day 155]
• Change from Baseline or Percent Change from Baseline AUC0-t [Срок оценки: Up to study Day 155]
• Change from Baseline or Percent Change from Baseline in CLr [Срок оценки: Up to study Day 155]
• Change from Baseline or Percent Change from Baseline in quality of life (QoL) Assessed via the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale, Version 4. [Срок оценки: Up to study Day 155]

Критерии участия

Критерии включения

• Male and female patients ≥18 years of age at the time of consent.
• A body mass index (BMI) within the range of 15 - 38 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2.
• Confirmation of IgA Nephropathy verified by biopsy performed within the previous three years.
• All patients must be vaccinated prior to dosing with MenACWY Menactra® polysaccharide diphtheria toxoid conjugate vaccination against Neisseria meningitidis serogroups A, C, Y, and W-135. MenB meningococcal serogroup B vaccine (Bexsero®) will be administered per local guidelines.
• Hemoglobin ≥ 10g/dL and platelet count ≥ 100,000/mm3
• Female and male participates must agree to use contraceptives

Критерии исключения

• Evidence of severe urinary obstruction or difficulty in voiding; any urinary tract disorder other than IgAN at screening and before dosing with NM8074.
• Require dialysis or plasma exchange within 12 weeks prior to screening.
• Presence of crescent formation in ≥50% of glomeruli assessed on renal biopsy.
• History of bone marrow, hematopoietic stem cells, or solid organ transplantation.
• Use of other investigational drugs at the time of enrolment, or within 5 half-lives of enrolment or within 3 months to study day 1 whichever is longer.
• Severe concurrent co-morbidities not amenable to active treatment, e.g., patients with severe kidney disease (CKD stage 4, chronic dialysis).
• Clinically significant abnormal ECG during screening.
• Currently active systemic infection or suspicion of active bacterial, viral, or fungal infection within 2 weeks prior to first dose, or history of unexplained, recurrent bacterial infections.
• Has a currently active or known history of meningococcal disease or N. meningitidis infection.
• Clinically significant medical or psychological conditions or risk factors that, as per the Investigator's judgment, could hinder the patient's participation in the study, introduce additional risks for the patient, or complicate the evaluation of the patient or study outcomes.
• Pregnant, planning to become pregnant, or nursing female subjects.
• Females with a positive pregnancy test result at Screening or on Day 1.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Kim SJ, Koo HM, Lim BJ, Oh HJ, Yoo DE, Shin DH, Lee MJ, Doh FM, Park JT, Yoo TH, Kang SW, Choi KH, Jeong HJ, Han SH. Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy. PLoS One. 2012;7(7):e40495. doi: 10.1371/journal.pone.0040495. Epub 2012 Jul 6. PMID 22792353
• Lafayette RA, Kelepouris E. Immunoglobulin A Nephropathy: Advances in Understanding of Pathogenesis and Treatment. Am J Nephrol. 2018;47 Suppl 1:43-52. doi: 10.1159/000481636. Epub 2018 May 31. PMID 29852501
• Duval A, Caillard S, Fremeaux-Bacchi V. The complement system in IgAN: mechanistic context for therapeutic opportunities. Nephrol Dial Transplant. 2023 Nov 30;38(12):2685-2693. doi: 10.1093/ndt/gfad140. PMID 37385820
• Medjeral-Thomas NR, Cook HT, Pickering MC. Complement activation in IgA nephropathy. Semin Immunopathol. 2021 Oct;43(5):679-690. doi: 10.1007/s00281-021-00882-9. Epub 2021 Aug 11. PMID 34379175
• Stefan G, Jullien P, Masson I, Alamartine E, Mariat C, Maillard N. Circulating alternative pathway complement cleavage factor Bb is associated with vascular lesions and outcomes in IgA nephropathy. Nephrol Dial Transplant. 2023 Nov 8;38(Suppl 2):ii11-ii18. doi: 10.1093/ndt/gfad163. PMID 37816675

Идентификаторы

NCT: NCT06454110 · NM8074-IGAN-601

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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