Clinical trial NCT03453619: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: IgA Nephropathy
Lupus Nephritis
Membranous Nephropathy
C3 Glomerulonephritis
Dense Deposit Disease
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-03-05
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Part A: Change From Baseline in Proteinuria at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Part B: Change From Baseline in Proteinuria at Week 168
timeFrame: Baseline (Part A, Week 48) and Week 168
Secondary outcomes:
measure: 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
timeFrame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
measure: 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
timeFrame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
measure: Parts A and B: Change From Baseline in C3a Concentrations at Week 48 of Part A and Week 168 of Part B
timeFrame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
measure: Parts A and B: Change From Baseline in Serum Albumin Levels at Week 48 of Part A and Week 168 of Part B
timeFrame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
measure: Parts A and B: Number of Subjects With Complete Clinical Remission at Week 48 of Part A and Week 168 of Part B
timeFrame: Part A: Week 48; Part B: Week 168
measure: 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
timeFrame: Part A: Baseline (Day 1) and Week 48; Part B: Baseline (Part A, Week 48) and Week 168
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: HealthONE Physician Care, Rocky Mountain Hospital for Children
state: Colorado
city: Washington
country: United States
facility: Washington Nephrology Associates
state: District of Columbia
city: Coral Gables
country: United States
facility: Horizon Research Group
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Jeffersonville
country: United States
facility: American Research LLC
state: Indiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology LLC
state: Louisiana
city: Takoma Park
country: United States
facility: Washington Nephrology Associates
state: Maryland
city: Kansas City
country: United States
facility: Clinical Research Consultants
state: Missouri
city: Bronx
country: United States
facility: Davita Clinical Research
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Wilmington
country: United States
facility: Southeastern Nephrology Associates
state: North Carolina
city: Memphis
country: United States
facility: University Clinical Health
state: Tennessee
city: Alexandria
country: United States
facility: Washington Nephrology Associates
state: Virginia
city: Chesapeake
country: United States
facility: Davita Clinical Research
state: Virginia
city: Wauwatosa
country: United States
facility: Milwaukee Nephrologists
state: Wisconsin
Study officials:
References: