A Phase I Study to Assess the Safety of Pegcetacoplan (APL-2) as an Add-On to Standard of Care in Subjects With PNH

Apellis Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Treatments: Drug: Pegcetacoplan

Study type: Interventional

Funder types: Industry

Identifiers

NCT02264639

APL-CP0514

Details and patient eligibility

About

This study will be the initial exploration of pegcetacoplan in patients with PNH. The assessments of the safety, tolerability, PK, and PD following administration of single and multiples doses of pegcetacoplan will guide decisions to further develop the drug.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or Female
• At least 18 years of age
• Weigh >55 kg
• Diagnosed with PNH
• On treatment with eculizumab (Soliris®) for at least 3 months
• Hb < 10 g/dL at screening OR have received at least one transfusion within 12 months prior to screening
• Platelet count of >30,000/mm3
• Absolute neutrophil count > 500/mm3
• Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study (see below)
• Males with female partners of child bearing potential must agree to use protocol defined methods of contraception (see below) and agree to refrain from donating sperm for the duration of the study
• Willing and able to give informed consent

Exclusion criteria

• Active bacterial infection
• Known infection with hepatitis B, C or HIV
• Hereditary complement deficiency
• History of bone marrow transplantation
• Participation in any other investigational drug trial or exposure to other investigational agent, device or procedure within 30 days
• Evidence of QTcF prolongation defined as > 450 ms for males and > 470 ms for females at screening
• Creatinine clearance (CrCl) < 50 mL/min (Cockcroft-Gault formula) at screening
• Breast-feeding women
• History of meningococcal disease
• No vaccination against N. meningitidis types A, C, W, Y and B (administered as two separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, respectively) and Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 (Visit 2) dosing.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

9 participants in 4 patient groups

Cohort 1

Experimental group

Description:

First Dose 25mg, Repeated Dose 5 mg/day

Treatment:

Drug: Pegcetacoplan

Cohort 2

Experimental group

Description:

First Dose 50 mg, Repeated Dose 30 mg/day

Treatment:

Drug: Pegcetacoplan

Cohort 3

Experimental group

Description:

Repeated Dose 180 mg/day

Treatment:

Drug: Pegcetacoplan

Cohort 4

Experimental group

Description:

Repeated Dose 270 mg/day

Treatment:

Drug: Pegcetacoplan