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

• ClinicalTrials.gov Identifier: NCT03453619
• Recruitment Status: Unknown
• First Posted: March 5, 2018
• Last Update Posted: September 2, 2020
• Sponsor: Apellis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Apellis Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: February 27, 2018
• First Posted Date: March 5, 2018
• Last Update Posted Date: September 2, 2020
• Actual Study Start Date: January 22, 2018
• Actual Primary Completion Date: April 16, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 5, 2019)

Proteinuria [ Time Frame: 48 weeks ]

Proteinuria reduction by 50%, calculated by the change in uPCR from baseline to Week 48.

• Original Primary Outcome Measures (submitted: February 27, 2018): Changes in Proteinuria [ Time Frame: 16 weeks ]

Current Secondary Outcome Measures (submitted: December 5, 2019)

• Changes of Disease Specific Biomarkers [ Time Frame: Week 48 ]
• Complete clinical remission defined as normalization of proteinuria as defined by <200 mg/g uPCR at Week 48 [ Time Frame: Week 48 ]
• Stabilization or improvement in estimated Glomerular Filtration Rate (eGFR) from baseline to Week 48 [ Time Frame: Week 48 ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Drug: APL-2

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

Study Arms

Experimental: APL-2

Open Label, Study Drug, APL-2

Intervention: Drug: APL-2

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: December 5, 2019): 21
• Original Estimated Enrollment (submitted: February 27, 2018): 36
• Estimated Study Completion Date: December 2022
• Actual Primary Completion Date: April 16, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03453619
• Other Study ID Numbers: APL2-201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Apellis Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Apellis Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Apellis Pharmaceuticals, Inc.
• Verification Date: August 2020