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

Phase 2

Completed

Conditions: IgA Nephropathy
Membranous Nephropathy
Dense Deposit Disease
Lupus Nephritis
C3 Glomerulonephritis

Interventions: Drug: APL-2

Registration Number: NCT03453619

Lead Sponsor: Apellis Pharmaceuticals, Inc.

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
APL-2	APL-2	Open Label, Study Drug, APL-2

Primary Outcome Measures

Name	Time	Method
Part A: Change From Baseline in Proteinuria at Week 48	Baseline (Day 1) and Week 48	Change from baseline in proteinuria was assessed based on urinary protein-to-creatinine ratio (uPCR). Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Part B: Change From Baseline in Proteinuria at Week 168	Baseline (Part A, Week 48) and Week 168	Change from baseline in proteinuria was assessed based on uPCR. Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.

Secondary Outcome Measures

Name	Time	Method
Parts A and B: Change From Baseline in Serum Complement 3 (C3) Levels at Week 48 of Part A and Week 168 of Part B	Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168	Blood samples were collected to measure serum C3 levels. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Parts A and B: Change From Baseline in Alternative Pathway Hemolytic Assay (AH50) Activity at Week 48 of Part A and Week 168 of Part B	Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168	Blood samples were collected to measure AH50 activity. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Parts A and B: Number of Subjects With Complete Clinical Remission at Week 48 of Part A and Week 168 of Part B	Part A: Week 48; Part B: Week 168	The complete clinical remission was defined as normalization of proteinuria as defined by \<200 mg/g uPCR.
Parts A and B: Change From Baseline in C3a Concentrations at Week 48 of Part A and Week 168 of Part B	Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168	Blood samples were collected to measure C3a concentrations. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Parts A and B: Change From Baseline in Serum Albumin Levels at Week 48 of Part A and Week 168 of Part B	Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168	Blood samples were collected to measure serum albumin levels. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.
Parts A and B: Number of Subjects With Stabilization or Improvement in Estimated Glomerular Filtration Rate (eGFR) From Baseline at Week 48 of Part A and Week 168 of Part B	Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168	The eGFR stabilization or improvement was defined as an eGFR value that was no more than a 25% decrease relative to baseline. Part A baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Part B baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.

Trial Locations

Locations (14): Horizon Research Group
🇺🇸
Coral Gables, Florida, United States
Northwest Louisiana Nephrology LLC
🇺🇸
Shreveport, Louisiana, United States
Washington Nephrology Associates
🇺🇸
Alexandria, Virginia, United States
Stanford University
🇺🇸
Stanford, California, United States
HealthONE Physician Care, Rocky Mountain Hospital for Children
🇺🇸
Denver, Colorado, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
American Research LLC
🇺🇸
Jeffersonville, Indiana, United States
Davita Clinical Research
🇺🇸
Chesapeake, Virginia, United States
University Clinical Health
🇺🇸
Memphis, Tennessee, United States
Westchester Medical Center
🇺🇸
Valhalla, New York, United States
Milwaukee Nephrologists
🇺🇸
Wauwatosa, Wisconsin, United States
Southeastern Nephrology Associates
🇺🇸
Wilmington, North Carolina, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Clinical Research Consultants
🇺🇸
Kansas City, Missouri, United States