Clinical trial NCT06454110: Study of NM8074 in Patients With Immunoglobulin A Nephropathy (IgAN)
Official title: A Phase II, Open-Label Study of NM8074 in Patients With Immunoglobulin A Nephropathy (IgAN)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: IgA Nephropathy
Lead sponsor: NovelMed Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-06-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study will enroll a planned total of 10 patients as subjects for the trial, with extra enrollment if needed, at the discretion of the Investigator. 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.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change from Baseline or Percent Change from Baseline in urine protein to creatinine concentration ratio
timeFrame: Up to Study Day 99
Secondary outcomes:
measure: Change from Baseline or Percent Change from Baseline in eGFR
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in Serum Creatinine
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in Hematuria
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in Urine Albumin to Creatinine concentration ratio
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in Bb plasma levels
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in sC5b-9 plasma levels
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in UPCR
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in Tmax
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in Cmax
timeFrame: Up to study Day 155
measure: Change from Baseline or Percent Change from Baseline AUC0-t
timeFrame: Up to study Day 155
measure: Change from Baseline or Percent Change from Baseline in CLr
timeFrame: Up to study Day 155
measure: 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.
timeFrame: Up to study Day 155
measure: Change from Baseline or Percent Change from Baseline in Quality of Life (QoL) Assessed via the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 Scale (QLQ- C30), Version 3.0
timeFrame: Up to study Day 155
Other outcomes:
measure: Change from Baseline or Percent Change from Baseline in Classical Pathway (CP) modulation
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in Factor B levels
timeFrame: Up to Study Day 155
measure: Change from Baseline or Percent Change from Baseline in plasma concentration of NM8074
timeFrame: Up to Study Day 155
measure: Maximum plasma concentration (Cmax)
timeFrame: Up to Study Day 155
measure: Time corresponding to Cmax (tmax)
timeFrame: Up to Study Day 155
measure: Area under the drug concentration-time curves (AUC0-t)
timeFrame: Up to Study Day 155
Locations:
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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(Supplement_2):ii11-ii18. doi: 10.1093/ndt/gfad163.