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

NCT ID: NCT03453619

Last Updated: 2025-02-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-26
• Study Completion Date: 2023-08-26

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

Conditions

IgA Nephropathy; Lupus Nephritis; Membranous Nephropathy; C3 Glomerulonephritis; Dense Deposit Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

APL-2

Open Label, Study Drug, APL-2

Group Type: EXPERIMENTAL

APL-2

Intervention Type: DRUG

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

Interventions

APL-2

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Apellis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Stanford University

Stanford, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

HealthONE Physician Care, Rocky Mountain Hospital for Children

Denver, Colorado, United States

Washington Nephrology Associates

Washington D.C., District of Columbia, United States

Horizon Research Group

Coral Gables, Florida, United States

Emory University

Atlanta, Georgia, United States

American Research LLC

Jeffersonville, Indiana, United States

Northwest Louisiana Nephrology LLC

Shreveport, Louisiana, United States

Washington Nephrology Associates

Takoma Park, Maryland, United States

Clinical Research Consultants

Kansas City, Missouri, United States

Davita Clinical Research

The Bronx, New York, United States

Westchester Medical Center

Valhalla, New York, United States

Southeastern Nephrology Associates

Wilmington, North Carolina, United States

University Clinical Health

Memphis, Tennessee, United States

Washington Nephrology Associates

Alexandria, Virginia, United States

Davita Clinical Research

Chesapeake, Virginia, United States

Milwaukee Nephrologists

Wauwatosa, Wisconsin, United States

Countries

United States

References

Budge KL, Verlato A, Bin S, Salem FE, Perin L, La Manna G, Zaza G, Fiaccadori E, Cantarelli C, Cravedi P. Decay-Accelerating Factor Restrains Complement Activation and Delays Progression of Murine cBSA-Induced Membranous Nephropathy. Kidney360. 2023 Jun 1;4(6):e769-e776. doi: 10.34067/KID.0000000000000122. Epub 2023 Apr 8.

Reference Type: DERIVED

PMID: 37036696 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

APL2-201

Identifier Type: -

Identifier Source: org_study_id