Study Assessing the Safety and Efficacy of Pegcetacoplan in Post-Transplant Recurrence of C3G or IC-MPGN (NOBLE)

• ClinicalTrials.gov Identifier: NCT04572854
• Recruitment Status: Active, not recruiting
• First Posted: October 1, 2020
• Last Update Posted: March 6, 2024
• Sponsor: Apellis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Apellis Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: September 29, 2020
• First Posted Date: October 1, 2020
• Last Update Posted Date: March 6, 2024
• Actual Study Start Date: February 23, 2021
• Actual Primary Completion Date: February 27, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 1, 2021): The primary efficacy endpoint is the proportion of subjects with reduction in C3c staining on renal biopsy after 12 weeks of treatment with pegcetacoplan. [ Time Frame: 12 weeks after randomization ]
• Original Primary Outcome Measures (submitted: September 29, 2020): The primary efficacy endpoint is the proportion of patients with reduction in C3c staining on renal biopsy after 12 weeks of treatment with pegcetacoplan. [ Time Frame: 12 weeks after enrollemtn ]

Current Secondary Outcome Measures (submitted: April 5, 2022)

• The proportion of subjects with reduction in C3c staining on renal biopsy [ Time Frame: 52 weeks after randomization ]
• The proportion of subjects with stabilization or improvement in estimated glomerular filtration rate (eGFR) [ Time Frame: 52 weeks after randomization ]
• The proportion of subjects with stabilization or improvement of serum creatinine concentration [ Time Frame: 52 weeks after randomization ]

Original Secondary Outcome Measures (submitted: September 29, 2020)

• The number and incidence of treatment-related adverse events (AEs) [ Time Frame: 52 weeks after enrollment ]
• The proportion of patients with reduction in C3c staining on renal biopsy [ Time Frame: 52 weeks after enrollment ]
• The proportion of patients achieving at least a 50% reduction in proteinuria, over time [ Time Frame: 52 weeks after enrollment ]
• The proportion of patients achieving complete clinical remission of proteinuria, defined as normalization of proteinuria [ Time Frame: 52 weeks after enrollment ]
• The proportion of patients with stabilization or improvement in estimated glomerular filtration rate (eGFR), over time [ Time Frame: 52 weeks after enrollment ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Assessing the Safety and Efficacy of Pegcetacoplan in Post-Transplant Recurrence of C3G or IC-MPGN
• Official Title: An Open-Label, Randomized, Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of Pegcetacoplan in the Treatment of Post-Transplant Recurrence of C3G or IC-MPGN
• Brief Summary: This is a Phase 2, multicenter, open-label, randomized, controlled study designed to evaluate the safety and efficacy of pegcetacoplan in patients who have post-transplant recurrence of C3G or IC-MPGN.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• C3G
• IC-MPGN
• Renal Transplant
• Complement 3 Glomerulopathy
• Complement 3 Glomerulopathy (C3G)
• Dense Deposit Disease (DDD)
• Membranoproliferative Glomerulonephritis
• Membranoproliferative Glomerulonephritis (MPGN)
• Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
• C3 Glomerulopathy
• C3 Glomerulonephritis
• Complement 3 Glomerulonephritis

Intervention

Drug: Pegcetacoplan

Complement (C3) Inhibitor

Study Arms

• Experimental: Group 1
  Pegcetacoplan treatment of 1080 mg (sub-cutaneous infusion) twice weekly will be given throughout the entire study.
  Intervention: Drug: Pegcetacoplan
• Group 2
  No intervention given during the randomized controlled portion of the study (through week 12). After week 12, subjects will receive pegcetacoplan treatment.
  Intervention: Drug: Pegcetacoplan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 5, 2024): 13
• Original Estimated Enrollment (submitted: September 29, 2020): 12
• Estimated Study Completion Date: January 2026
• Actual Primary Completion Date: February 27, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• At least 18 years of age at screening
• Must have clinical and pathologic evidence of recurrent C3G or IC-MPGN
• Stable (not improving) or worsening disease, in the opinion of the investigator, in the 2 months preceding the first dose of pegcetacoplan
• eGFR ≥15 mL/min/1.73 m2, calculated by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) creatinine equation for adults
• No more than 50% glomerulosclerosis or interstitial fibrosis on the screening renal allograft biopsy
• Stable regimen for recurrent C3G/IC-MPGN for at least 4 weeks prior to the screening renal allograft biopsy and from the time of the screening renal allograft biopsy until randomization
• Have received required vaccinations against N. meningitidis, S. pneumoniae, and H. influenzae (type B) or agree to receive vaccinations, if applicable vaccination records are not available. Vaccination is mandatory unless documented evidence exists that subjects are non-responders to vaccination.

Exclusion Criteria:

• Absolute neutrophil count <1000 cells/mm3 during screening
• Previous treatment with pegcetacoplan
• Evidence of rejection on the screening renal allograft biopsy that requires treatment
• Diagnosis or history of HIV, hepatitis B, or hepatitis C infection or positive serology at screening indicative of infection with any of these viruses
• Weight more than 100 kg at screening
• Hypersensitivity to pegcetacoplan or any of the excipients
• History of meningococcal disease
• Malignancy, except for the following:
• Cured basal or squamous cell skin cancer
• Curatively treated in situ disease
• Malignancy free and off treatment for ≥5 years
• Significant renal disease in the renal allograft secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, rejection, or a medication) that would, in the opinion of the investigator, confound interpretation of the study results
• Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days or 5 half-lives from the last dose of the investigational agent (whichever is longer) prior to screening
• Known or suspected hereditary fructose intolerance.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Brazil, France, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT04572854
• Other Study ID Numbers: APL2-C3G-204
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Apellis Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Apellis Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Apellis Pharmaceuticals, Inc.
• Verification Date: March 2024