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

IgA Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06454110
• Other study ID #: NM8074-IGAN-601
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 2025
• Est. completion date: July 2027

Study information

• Verified date: June 2024
• Source: NovelMed Therapeutics
• Contact: Rekha Bansal, PhD
• Phone: 2164402696
• Email: clinicalsae[@]novelmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: July 2027
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Kidney Diseases

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
NovelMed Therapeutics

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Change from Baseline or Percent Change from Baseline in Factor B levels		Up to Study Day 155
Other	Change from Baseline or Percent Change from Baseline in plasma concentration of NM8074		Up to Study Day 155
Other	Maximum plasma concentration (Cmax)		Up to Study Day 155
Other	Time corresponding to Cmax (tmax)		Up to Study Day 155
Other	Area under the drug concentration-time curves (AUC0-t)		Up to Study Day 155
Primary	Change from Baseline or Percent Change from Baseline in urine protein to creatinine concentration ratio		Up to Study Day 99
Secondary	Change from Baseline or Percent Change from Baseline in eGFR		Up to Study Day 155
Secondary	Change from Baseline or Percent Change from Baseline in Serum Creatinine		Up to Study Day 155
Secondary	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
Secondary	Change from Baseline or Percent Change from Baseline in Urine Albumin to Creatinine concentration ratio		Up to Study Day 155
Secondary	Change from Baseline or Percent Change from Baseline in Bb plasma levels		Up to Study Day 155
Secondary	Change from Baseline or Percent Change from Baseline in sC5b-9 plasma levels		Up to Study Day 155
Secondary	Change from Baseline or Percent Change from Baseline in UPCR		Up to Study Day 155
Secondary	Change from Baseline or Percent Change from Baseline in Tmax		Up to Study Day 155
Secondary	Change from Baseline or Percent Change from Baseline in Cmax		Up to study Day 155
Secondary	Change from Baseline or Percent Change from Baseline AUC0-t		Up to study Day 155
Secondary	Change from Baseline or Percent Change from Baseline in CLr		Up to study Day 155
Secondary	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
Secondary	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