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

Primary Purpose

IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
APL-2
Sponsored by
Apellis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for IgA Nephropathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford University
  • Children's Hospital Colorado
  • HealthONE Physician Care, Rocky Mountain Hospital for Children
  • Washington Nephrology Associates
  • Horizon Research Group
  • Emory University
  • American Research LLC
  • Northwest Louisiana Nephrology LLC
  • Washington Nephrology Associates
  • Clinical Research Consultants
  • Davita Clinical Research
  • Westchester Medical Center
  • Southeastern Nephrology Associates
  • University Clinical Health
  • Washington Nephrology Associates
  • Davita Clinical Research
  • Milwaukee Nephrologists

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

APL-2

Arm Description

Open Label, Study Drug, APL-2

Outcomes

Primary Outcome Measures

Proteinuria
Proteinuria reduction from baseline to Week 48, based on urinary protein-to-creatinine ratio (uPCR).

Secondary Outcome Measures

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

Full Information

First Posted
February 27, 2018
Last Updated
April 3, 2023
Sponsor
Apellis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03453619
Brief Title
Phase II Study Assessing Safety and Efficacy of APL-2 in Glomerulopathies
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 22, 2018 (Actual)
Primary Completion Date
April 16, 2020 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Apellis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy, C3 Glomerulonephritis, Dense Deposit Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
APL-2
Arm Type
Experimental
Arm Description
Open Label, Study Drug, APL-2
Intervention Type
Drug
Intervention Name(s)
APL-2
Intervention Description
APL-2 administered as a daily subcutaneous infusion for 48 weeks
Primary Outcome Measure Information:
Title
Proteinuria
Description
Proteinuria reduction from baseline to Week 48, based on urinary protein-to-creatinine ratio (uPCR).
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Changes of Disease Specific Biomarkers (serum C3 levels, AH50 and C3a concentrations, serum albumin levels)
Time Frame
Week 48
Title
Complete clinical remission defined as normalization of proteinuria as defined by <200 mg/g uPCR at Week 48
Time Frame
Week 48
Title
Stabilization or improvement in estimated Glomerular Filtration Rate (eGFR) from baseline to Week 48
Time Frame
Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
HealthONE Physician Care, Rocky Mountain Hospital for Children
City
Denver
State/Province
Colorado
ZIP/Postal Code
80205
Country
United States
Facility Name
Washington Nephrology Associates
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Horizon Research Group
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33134
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
American Research LLC
City
Jeffersonville
State/Province
Indiana
ZIP/Postal Code
47130
Country
United States
Facility Name
Northwest Louisiana Nephrology LLC
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71101
Country
United States
Facility Name
Washington Nephrology Associates
City
Takoma Park
State/Province
Maryland
ZIP/Postal Code
20912
Country
United States
Facility Name
Clinical Research Consultants
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Davita Clinical Research
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Westchester Medical Center
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Southeastern Nephrology Associates
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
University Clinical Health
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Washington Nephrology Associates
City
Alexandria
State/Province
Virginia
ZIP/Postal Code
22304
Country
United States
Facility Name
Davita Clinical Research
City
Chesapeake
State/Province
Virginia
ZIP/Postal Code
23320
Country
United States
Facility Name
Milwaukee Nephrologists
City
Wauwatosa
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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