Phase II Study Assessing Safety and Efficacy of APL-2 in Glomerulopathies

A Phase 2 Study to Evaluate the Safety and Biologic Activity of APL- 2 in Patients With IgA Nephropathy, Lupus Nephritis, Primary Membranous Nephropathy, or C3 Glomerulopathy (C3 Glomerulonephritis and Dense Deposit Disease)

This is a Phase II trial assessing the safety and preliminary efficacy of daily APL-2 subcutaneous infusion administered for 16 weeks with a 6 month safety follow up, in patients with glomerulopathies

Study Overview

• Status: Active, not recruiting
• Conditions: Lupus Nephritis; IgA Nephropathy; Membranous Nephropathy; C3 Glomerulonephritis; Dense Deposit Disease
• Intervention / Treatment: Drug: APL-2

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
    • Denver, Colorado, United States, 80205
      • HealthONE Physician Care, Rocky Mountain Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Washington Nephrology Associates
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Horizon Research Group
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Indiana
    • Jeffersonville, Indiana, United States, 47130
      • American Research LLC
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology LLC
  • Maryland
    • Takoma Park, Maryland, United States, 20912
      • Washington Nephrology Associates
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants
  • New York
    • Bronx, New York, United States, 10461
      • DaVita Clinical Research
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Southeastern Nephrology Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • University Clinical Health
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Washington Nephrology Associates
    • Chesapeake, Virginia, United States, 23320
      • DaVita Clinical Research
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Milwaukee Nephrologists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of at least 18 years of age at screening (16 years of age for C3G), able to provide written informed consent, and able to understand and comply with all scheduled procedures and other requirements of the study by the opinion of Principal Investigator (PI)

• Patients must have a diagnosis of IgAN, LN, Primary MN, or C3G confirmed by renal biopsy and required measurements performed prior to study participation

  • IgAN: Prior biopsy results for C3 and C4d staining should be made available
  • LN: Diagnostic biopsy showing proliferative focal, diffuse, or membranous lesions (Class III, IV or V, respectively) by renal biopsy. Subject should have either a biopsy in the last 6 months, or evidence of disease activity (nephritic changes on urinalysis or nephrotic changes)
  • Primary MN: PLA2R positive titer plus nephrotic range proteinuria (defined as uPCR >2350 mg/g)
  • C3G plus one of the following: Low serum C3 level or historical renal biopsy within the last 3 years
• Have proteinuria >750 mg/g (calculated by uPCR on 24 hour urine collection) collected during the first screening visit (Visit 3a).
• eGFR≥30mL/min/1.73 m2 calculated by CKD-EPI creatinine equation at screening visit 3a and currently not on dialysis
• Must have stable or worsening renal disease, on stable and optimized treatment, in the opinion of the PI, for at least 2 months prior to the first dose of APL-2 (Visit 4); treatments may include, but are not limited to, immunosuppressive agents, anti-hypertensives and/or anti-proteinurics.
• Willing to receive vaccinations against Neisseria meningitidis at least 2 weeks prior to dosing on Day 1 with a booster on Day 56 (for both vaccinations) and Pneumococcal and Hib vaccines at least 2 weeks prior to dosing on Day 1.

Exclusion Criteria:

• Absolute neutrophil count <1000 cells/mm3 at screening Visits 3a and 3b
• ALT or AST >3.0 x the upper limit of normal at screening Visits 3a and 3b
• Previous treatment with APL-2
• History of solid organ transplant
• Diagnosis of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or positive serology at screening Visits 3a and 3b (previous HBV or HCV diagnosis cleared by treatment is allowed)
• Renal disease secondary to another condition (e.g. infection, malignancy, monoclonal gammopathy, or a medication)
• Presence or suspicion of active bacterial or viral infection or severe recurrent bacterial infections
• Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening period
• Unwillingness to receive or intolerant of SC infusions of study medication or known allergy to ingredients in APL-2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APL-2; Open Label, Study Drug, APL-2	Drug: APL-2; APL-2 administered as a daily subcutaneous infusion for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proteinuria	Proteinuria reduction from baseline to Week 48, based on urinary protein-to-creatinine ratio (uPCR).	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Complete clinical remission defined as normalization of proteinuria as defined by <200 mg/g uPCR at Week 48	Week 48
Stabilization or improvement in estimated Glomerular Filtration Rate (eGFR) from baseline to Week 48	Week 48
Changes of Disease Specific Biomarkers (serum C3 levels, AH50 and C3a concentrations, serum albumin levels)	Week 48

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2018
• Primary Completion (Actual): April 16, 2020
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: February 27, 2018
• First Submitted That Met QC Criteria: February 27, 2018
• First Posted (Actual): March 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Kidney Diseases; Glomerulonephritis; Nephritis; Lupus Nephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulonephritis, Membranoproliferative
• Other Study ID Numbers: APL2-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No