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

Lupus Nephritis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03453619
• Other study ID #: APL2-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 22, 2018
• Est. completion date: December 2023

Study information

• Verified date: April 2023
• Source: Apellis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: December 2023
• Est. primary completion date: April 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• C3 Glomerulonephritis
• Dense Deposit Disease
• Glomerulonephritis
• Glomerulonephritis, IGA
• Glomerulonephritis, Membranoproliferative
• Glomerulonephritis, Membranous
• IgA Nephropathy
• Kidney Diseases
• Lupus Nephritis
• Membranous Nephropathy
• Nephritis

Intervention

Drug:
• APL-2
APL-2 administered as a daily subcutaneous infusion for 48 weeks

Locations

Country	Name	City	State
United States	Washington Nephrology Associates	Alexandria	Virginia
United States	Emory University	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Davita Clinical Research	Bronx	New York
United States	Davita Clinical Research	Chesapeake	Virginia
United States	Horizon Research Group	Coral Gables	Florida
United States	HealthONE Physician Care, Rocky Mountain Hospital for Children	Denver	Colorado
United States	American Research LLC	Jeffersonville	Indiana
United States	Clinical Research Consultants	Kansas City	Missouri
United States	University Clinical Health	Memphis	Tennessee
United States	Northwest Louisiana Nephrology LLC	Shreveport	Louisiana
United States	Stanford University	Stanford	California
United States	Washington Nephrology Associates	Takoma Park	Maryland
United States	Westchester Medical Center	Valhalla	New York
United States	Washington Nephrology Associates	Washington	District of Columbia
United States	Milwaukee Nephrologists	Wauwatosa	Wisconsin
United States	Southeastern Nephrology Associates	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Apellis Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proteinuria	Proteinuria reduction from baseline to Week 48, based on urinary protein-to-creatinine ratio (uPCR).	48 weeks
Secondary	Changes of Disease Specific Biomarkers (serum C3 levels, AH50 and C3a concentrations, serum albumin levels)		Week 48
Secondary	Complete clinical remission defined as normalization of proteinuria as defined by <200 mg/g uPCR at Week 48		Week 48
Secondary	Stabilization or improvement in estimated Glomerular Filtration Rate (eGFR) from baseline to Week 48		Week 48