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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NM8074 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline or Percent Change from Baseline in urine protein to creatinine concentration ratio | Up to Study Day 99 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline or Percent Change from Baseline in eGFR | Up to Study Day 155 | |
| Change from Baseline or Percent Change from Baseline in Serum Creatinine | Up to Study Day 155 | |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline or Percent Change from Baseline in Classical Pathway (CP) modulation | NM8074-mediated CP inhibition is measure via a complement CP ELISA-based assay measuring MAC formation. | Up to Study Day 155 |
| Change from Baseline or Percent Change from Baseline in Factor B levels |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rekha Bansal, PhD | Contact | 2164402696 | clinicalsae@novelmed.com |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22792353 | Background | 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. | |
| 29852501 | Background |
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| ID | Term |
|---|---|
| D005922 | Glomerulonephritis, IGA |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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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.
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| Change from Baseline or Percent Change from Baseline in Hematuria |
Measured through red blood cells present in urine from urinalysis |
| Up to Study Day 155 |
| Change from Baseline or Percent Change from Baseline in Urine Albumin to Creatinine concentration ratio | Up to Study Day 155 |
| Change from Baseline or Percent Change from Baseline in Bb plasma levels | Up to Study Day 155 |
| Change from Baseline or Percent Change from Baseline in sC5b-9 plasma levels | Up to Study Day 155 |
| Change from Baseline or Percent Change from Baseline in UPCR | Up to Study Day 155 |
| Change from Baseline or Percent Change from Baseline in Tmax | Up to Study Day 155 |
| Change from Baseline or Percent Change from Baseline in Cmax | Up to study Day 155 |
| Change from Baseline or Percent Change from Baseline AUC0-t | Up to study Day 155 |
| Change from Baseline or Percent Change from Baseline in CLr | 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. | The FACIT-fatigue scale is a 13-item patient-reported measure of fatigue with a 7-day recall period. Items are scored on a 0 - 4 response scale ranging from "Not at all" to "Very much so". All items are summed to create a single fatigue score with a range from 0 to 52 with a better quality of life indicated by a higher score. | Up to study Day 155 |
| 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 | All EORTC QLQ-C30 scales and single-item measures range from 0 to 100. This includes 3 symptom scales (fatigue, pain, nausea and vomiting), 5 functional scales (physical, role, cognitive, emotional, and social), single-item questions addressing symptoms like insomnia, dyspnea, loss of appetite, and others that are commonly reported by cancer patients, and the perceived financial impact of the disease. A higher score is associated with a greater quality of life for global health status | Up to study Day 155 |
| Up to Study Day 155 |
| Change from Baseline or Percent Change from Baseline in plasma concentration of NM8074 | Up to Study Day 155 |
| Maximum plasma concentration (Cmax) | Up to Study Day 155 |
| Time corresponding to Cmax (tmax) | Up to Study Day 155 |
| Area under the drug concentration-time curves (AUC0-t) | Up to Study Day 155 |
| 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. |
| 37385820 | Background | 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. |
| 34379175 | Background | 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. |
| 37816675 | Background | 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. |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |