Study of NM8074 in Adult C3 Glomerulopathy Patients

Official title

A Phase Ib, Open Label, Dose Escalation Study of NM8074 in Subjects With C3 Glomerulopathy (C3G)

Overview

This is a Phase Ib, open-label, dose-escalation study designed to evaluate the safety, efficacy, and immunogenicity of NM8074 administered intravenously to patients with C3 Glomerulopathy.

Detailed description

The proposed study, NM8074-C3G-101, will enroll a planned number of 18 patients, with the potential to enroll more patients. There will be 3 cohorts with 6 patients each dosed at 5, 10, or 20 mg/kg depending on which cohort they are assigned to. Enrollment in the subsequent higher dose level cohort will occur after the previous cohort has been evaluated for safety.

Interventions

• Drug NM8074
  NM8074 will be administered as an intravenous infusion. Multiple dosing duration will range from 5 to 9 weeks.

Primary outcome measures

• Monitoring for incidence of Adverse Events (AEs)/Serious Adverse Events (SAEs) [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Change from Baseline or Percent Change from Baseline in Urine Protein to Creatine Concentration Ratio (UPCR) [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Change from Baseline or Percent Change from Baseline in Urine Albumin to Creatinine Concentration Ratio (UACR) [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Ratio to Baseline of UPCR and UACR [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Change from Baseline or Percent Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]

Secondary outcome measures (12)

• Percent Change from Baseline in Alternative Pathway (AP) of Complement Activity as Compared to Percent Change from Baseline in Classical Pathway (CP) of Complement Activity as Measured by Percent Change in Levels of Membrane Attack Complex (MAC) [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Percent Change from Baseline in Alternative Pathway (AP) of Complement Activity as Compared to Percent Change from Baseline in Classical Pathway (CP) of Complement Activity as Measured by Percent Change in Levels of Complement Component C3b [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Change from Baseline or Percent Change from Baseline in Serum C3 Levels [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Change from Baseline or Percent Change from Baseline in Glomerular Inflammation [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• 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. [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• 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 [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Changes in plasma concentration of NM8074 [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Maximum plasma concentration (Cmax) [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Time corresponding to Cmax (tmax) [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Area under the drug concentration-time curves (AUC0-t) [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Change from Baseline or Percent Change from Baseline in Levels of Complement Component C3b via Alternative Pathway (AP) of Complement Activity [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]
• Change from Baseline or Percent Change from Baseline in Levels of Membrane Attack Complex (MAC) via Alternative Pathway (AP) of Complement Activity [Time frame: Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3]

Eligibility criteria

Inclusion criteria

• Patients ≥ 18 and ≤ 65 years at the time of consent
• Diagnosis of C3 Glomerulopathy as confirmed by C3 nephropathy in biopsy within 12 months prior to enrollment
• Reduced serum C3 levels (defined as less than 0.85 x lower limit of the central laboratory normal range) at Screening
• Patients with confirmed proteinuria
• Willing and able to understand and complete informed consent procedures, including signing and dating the informed consent form (ICF), and comply with the study visit schedule
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must have a negative pregnancy test at screening and must agree to use highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug
• Males must agree to use contraceptives and refrain from donating sperm for the duration of the study
• Patients must have documentation of previous vaccination or be willing to be vaccinated prior to dosing with NM8074. All patients will be vaccinated against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae according to the most current Advisory Committee on Immunization Practices (ACIP) recommendations.
• Estimated glomerular filtration (eGFR) rate of ≤ 60 ml/min but ≥ 20 ml/min

Exclusion criteria

• Use of other investigational drugs at the time of enrollment
• Patients with other renal diseases that would interfere with interpretation of the study
• Estimated glomerular filtration rate of ≤ 20 mL/min/1.73m2 based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) at Screening
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal (xULN)
• Has a known history of meningococcal disease or N. meningitidis
• Currently active systemic infection or suspicion of active bacterial, viral, or fungal infection that requires antibiotic, antifungal, antiparasitic, or antiviral mediations
• Temperature > 38°C for more than two weeks prior to screening
• History of renal organ transplantation
• Pregnant, planning to become pregnant, or nursing female subjects
• C3G patients currently under complement blocker treatments
• Participation in any experimental small molecule or non-antibody therapy within 60 days prior to dosing on Day 1 (participation in observational studies and/or registry studies is permitted)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05647811 · NM8074-C3G-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗