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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 April 2023
• Main ID: NCT03453619
• Date of registration: 27/02/2018
• Prospective Registration: No
• Primary sponsor: Apellis Pharmaceuticals, Inc.
• Public title: Phase II Study Assessing Safety and Efficacy of APL-2 in Glomerulopathies
• Scientific 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)
• Date of first enrolment: January 22, 2018
• Target sample size: 21
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03453619
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Dense Deposit Disease

IgA Nephropathy

Lupus Nephritis

C3 Glomerulonephritis

Membranous Nephropathy

Intervention(s)

Drug: APL-2

Primary Outcome(s)

Proteinuria [Time Frame: 48 weeks]

Secondary Outcome(s)

Complete clinical remission defined as normalization of proteinuria as defined by <200 mg/g uPCR at Week 48 [Time Frame: Week 48]

Changes of Disease Specific Biomarkers (serum C3 levels, AH50 and C3a concentrations, serum albumin levels) [Time Frame: Week 48]

Stabilization or improvement in estimated Glomerular Filtration Rate (eGFR) from baseline to Week 48 [Time Frame: Week 48]

Secondary ID(s)

APL2-201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors