Study of NM8074 in Adult C3 Glomerulopathy Patients

C3 Glomerulopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05647811
• Other study ID #: NM8074-C3G-101
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: November 2024
• Est. completion date: July 2026

Study information

• Verified date: January 2024
• Source: NovelMed Therapeutics
• Contact: Rekha Bansal
• Phone: 216-440-2696
• Email: clinicalsae[@]novelmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

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

Eligibility

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)

Related Conditions & MeSH terms

• C3 Glomerulopathy

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
NovelMed Therapeutics

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from Baseline or Percent Change from Baseline in Levels of Complement Component C3b via Classical Pathway (CP) of Complement Activity.		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Other	Change from Baseline or Percent Change from Baseline in Levels of Membrane Attack Complex (MAC) via Classical Pathway (CP) of Complement Activity.		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Primary	Monitoring for incidence of Adverse Events (AEs)/Serious Adverse Events (SAEs)		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Primary	Change from Baseline or Percent Change from Baseline in Urine Protein to Creatine Concentration Ratio (UPCR)		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Primary	Change from Baseline or Percent Change from Baseline in Urine Albumin to Creatinine Concentration Ratio (UACR)		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Primary	Ratio to Baseline of UPCR and UACR	Derived from 24h urine collection	Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Primary	Change from Baseline or Percent Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	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)		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	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		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	Change from Baseline or Percent Change from Baseline in Serum C3 Levels		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	Change from Baseline or Percent Change from Baseline in Glomerular Inflammation	Measured by change from baseline or percent change from baseline in the C3G Histologic Index for Disease Activity - Combined C5b-9 Strata. Scores range from 0-21 where a decrease in score indicates improvement.	Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
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 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
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 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	Changes in plasma concentration of NM8074		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	Maximum plasma concentration (Cmax)		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	Time corresponding to Cmax (tmax)		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	Area under the drug concentration-time curves (AUC0-t)		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	Change from Baseline or Percent Change from Baseline in Levels of Complement Component C3b via Alternative Pathway (AP) of Complement Activity		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3
Secondary	Change from Baseline or Percent Change from Baseline in Levels of Membrane Attack Complex (MAC) via Alternative Pathway (AP) of Complement Activity		Up to Study Day 50 for Cohort 1 and up to study day 84 for Cohort 2 and 3