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

NCT03453619 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: APL2-201
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 17

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

Outcome Measures

Primary Outcomes (2)

• Part A: Change From Baseline in Proteinuria at 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.

  Baseline (Day 1) and Week 48

• Part B: Change From Baseline in Proteinuria at 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.

  Baseline (Part A, Week 48) and Week 168

Secondary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

APL-2

EXPERIMENTAL

Open Label, Study Drug, APL-2

Drug: APL-2

Interventions

APL-2 DRUG

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

APL-2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (17)

Stanford University

Stanford, California, 94305, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

HealthONE Physician Care, Rocky Mountain Hospital for Children

Denver, Colorado, 80205, United States

Location

Washington Nephrology Associates

Washington D.C., District of Columbia, 20037, United States

Location

Horizon Research Group

Coral Gables, Florida, 33134, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

American Research LLC

Jeffersonville, Indiana, 47130, United States

Location

Northwest Louisiana Nephrology LLC

Shreveport, Louisiana, 71101, United States

Location

Washington Nephrology Associates

Takoma Park, Maryland, 20912, United States

Location

Clinical Research Consultants

Kansas City, Missouri, 64111, United States

Location

Davita Clinical Research

The Bronx, New York, 10461, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

Southeastern Nephrology Associates

Wilmington, North Carolina, 28401, United States

Location

University Clinical Health

Memphis, Tennessee, 38103, United States

Location

Washington Nephrology Associates

Alexandria, Virginia, 22304, United States

Location

Davita Clinical Research

Chesapeake, Virginia, 23320, United States

Location

Milwaukee Nephrologists

Wauwatosa, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 37036696 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, IGA; Lupus Nephritis; Glomerulonephritis, Membranous; Glomerulonephritis, Membranoproliferative

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Apellis Clinical Trial Information Line
• Organization: Apellis Pharmaceuticals, Inc

clinicaltrials@apellis.com

1-833-284-6361

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2018
• First Posted: March 5, 2018
• Study Start: February 26, 2018
• Primary Completion: April 16, 2020
• Study Completion: August 26, 2023
• Last Updated: February 13, 2025
• Results First Posted: February 13, 2025

Record last verified: 2024-07

Locations

US (17)