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

Paroxysmal Nocturnal Hemoglobinuria (PNH) Clinical Trial

Official title:

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02264639
• Other study ID #: APL-CP0514
• Status: Completed
• Phase: Phase 1
• Start date: February 23, 2015
• Est. completion date: October 22, 2018

Study information

• Verified date: December 2020
• Source: Apellis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: October 22, 2018
• Est. primary completion date: October 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention

Drug:
• Pegcetacoplan
Complement (C3) Inhibitor

Locations

Country	Name	City	State
United States	John Hopkins Hospital	Baltimore	Maryland
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Cure 4 The Kids Foundation	Las Vegas	Nevada
United States	University of Southern California Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Lousiville	Louisville	Kentucky
United States	Lakes Research	Miami Lakes	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Apellis Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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).
Primary	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.
Primary	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.