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

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pegcetacoplan
Sponsored by
Apellis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria (PNH) focused on measuring PNH, Paroxysmal Nocturnal Hemoglobinuria, Complement inhibitor, Anemia, Hemoglobinuria, hematologic diseases, extravascular hemolysis (EVH), intravascular hemolysis (IVH), C3 inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • University of Southern California Norris Comprehensive Cancer Center
  • Lakes Research
  • University of Lousiville
  • John Hopkins Hospital
  • Cure 4 The Kids Foundation
  • Duke University Medical Center
  • Cleveland Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Arm Description

First Dose 25mg, Repeated Dose 5 mg/day

First Dose 50 mg, Repeated Dose 30 mg/day

Repeated Dose 180 mg/day

Repeated Dose 270 mg/day

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
October 8, 2014
Last Updated
December 14, 2020
Sponsor
Apellis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02264639
Brief Title
A Phase I Study to Assess the Safety of Pegcetacoplan (APL-2) as an Add-On to Standard of Care in Subjects With PNH
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).
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
February 23, 2015 (Actual)
Primary Completion Date
October 22, 2018 (Actual)
Study Completion Date
October 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Apellis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords
PNH, Paroxysmal Nocturnal Hemoglobinuria, Complement inhibitor, Anemia, Hemoglobinuria, hematologic diseases, extravascular hemolysis (EVH), intravascular hemolysis (IVH), C3 inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
First Dose 25mg, Repeated Dose 5 mg/day
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
First Dose 50 mg, Repeated Dose 30 mg/day
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Repeated Dose 180 mg/day
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
Repeated Dose 270 mg/day
Intervention Type
Drug
Intervention Name(s)
Pegcetacoplan
Other Intervention Name(s)
APL-2
Intervention Description
Complement (C3) Inhibitor
Primary Outcome Measure Information:
Title
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase
Description
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.
Time Frame
From single dose of study drug (Day 1) up to 30 days
Title
Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase
Description
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.
Time Frame
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).
Title
Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4
Description
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.
Time Frame
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.
Title
Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4
Description
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.
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Federico Grossi, MD, PhD
Organizational Affiliation
Apellis Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Southern California Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Lakes Research
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
University of Lousiville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
John Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Cure 4 The Kids Foundation
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89135
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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