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

An Open Label, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of APL-2 as an Add-On to Standard of Care in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).

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.

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Intervention / Treatment: Drug: Pegcetacoplan

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California Norris Comprehensive Cancer Center
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Lousiville
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • John Hopkins Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Cure 4 the Kids Foundation
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; First Dose 25mg, Repeated Dose 5 mg/day	Drug: Pegcetacoplan; Complement (C3) Inhibitor; Other Names: APL-2
Experimental: Cohort 2; First Dose 50 mg, Repeated Dose 30 mg/day	Drug: Pegcetacoplan; Complement (C3) Inhibitor; Other Names: APL-2
Experimental: Cohort 3; Repeated Dose 180 mg/day	Drug: Pegcetacoplan; Complement (C3) Inhibitor; Other Names: APL-2
Experimental: Cohort 4; Repeated Dose 270 mg/day	Drug: Pegcetacoplan; Complement (C3) Inhibitor; Other Names: APL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase	TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.	From single dose of study drug (Day 1) up to 30 days
Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase	TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.	From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).
Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4	Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.	Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4	Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.	Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2015
• Primary Completion (Actual): October 22, 2018
• Study Completion (Actual): October 22, 2018

Study Registration Dates

• First Submitted: October 8, 2014
• First Submitted That Met QC Criteria: October 10, 2014
• First Posted (Estimate): October 15, 2014

Study Record Updates

• Last Update Posted (Actual): January 8, 2021
• Last Update Submitted That Met QC Criteria: December 14, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Anemia; PNH; Paroxysmal Nocturnal Hemoglobinuria; Complement inhibitor; Hemoglobinuria; hematologic diseases; extravascular hemolysis (EVH); intravascular hemolysis (IVH); C3 inhibitor
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: APL-CP0514

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No