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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

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ClinicalTrials.gov Identifier: NCT02264639
Recruitment Status : Completed
First Posted : October 15, 2014
Results First Posted : January 8, 2021
Last Update Posted : January 8, 2021
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE October 8, 2014
First Posted Date  ICMJE October 15, 2014
Results First Submitted Date  ICMJE July 31, 2020
Results First Posted Date  ICMJE January 8, 2021
Last Update Posted Date January 8, 2021
Actual Study Start Date  ICMJE February 23, 2015
Actual Primary Completion Date October 22, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 14, 2020)
  • Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase [ Time Frame: From single dose of study drug (Day 1) up to 30 days ]
    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 [ 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). ]
    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 [ 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. ]
    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 [ 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. ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 10, 2014)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability. [ Time Frame: Four months ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2014)
PK Parameters [ Time Frame: Four months ]
  • Cmax
  • Maximum Concentration (Cmax)
  • Time to Cmax (Tmax)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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).
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Paroxysmal Nocturnal Hemoglobinuria (PNH)
Intervention  ICMJE Drug: Pegcetacoplan
Complement (C3) Inhibitor
Other Name: APL-2
Study Arms  ICMJE
  • Experimental: Cohort 1
    First Dose 25mg, Repeated Dose 5 mg/day
    Intervention: Drug: Pegcetacoplan
  • Experimental: Cohort 2
    First Dose 50 mg, Repeated Dose 30 mg/day
    Intervention: Drug: Pegcetacoplan
  • Experimental: Cohort 3
    Repeated Dose 180 mg/day
    Intervention: Drug: Pegcetacoplan
  • Experimental: Cohort 4
    Repeated Dose 270 mg/day
    Intervention: Drug: Pegcetacoplan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 8, 2020)
9
Original Estimated Enrollment  ICMJE
 (submitted: October 10, 2014)
8
Actual Study Completion Date  ICMJE October 22, 2018
Actual Primary Completion Date October 22, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02264639
Other Study ID Numbers  ICMJE APL-CP0514
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  ICMJE Not Provided
Responsible Party Apellis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Apellis Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Federico Grossi, MD, PhD Apellis Pharmaceuticals, Inc.
PRS Account Apellis Pharmaceuticals, Inc.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP