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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria (PNH) Drug: Pegcetacoplan Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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).
Actual Study Start Date : February 23, 2015
Actual Primary Completion Date : October 22, 2018
Actual Study Completion Date : October 22, 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1
First Dose 25mg, Repeated Dose 5 mg/day
 Drug: Pegcetacoplan
Complement (C3) Inhibitor
Other Name: APL-2
Experimental: Cohort 2
First Dose 50 mg, Repeated Dose 30 mg/day
 Drug: Pegcetacoplan
Complement (C3) Inhibitor
Other Name: APL-2
Experimental: Cohort 3
Repeated Dose 180 mg/day
 Drug: Pegcetacoplan
Complement (C3) Inhibitor
Other Name: APL-2
Experimental: Cohort 4
Repeated Dose 270 mg/day
 Drug: Pegcetacoplan
Complement (C3) Inhibitor
Other Name: APL-2


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02264639


Locations
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United States, California
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, Florida
Lakes Research
Miami Lakes, Florida, United States, 33014
United States, Kentucky
University of Lousiville
Louisville, Kentucky, United States, 40202
United States, Maryland
John Hopkins Hospital
Baltimore, Maryland, United States, 21231
United States, Nevada
Cure 4 The Kids Foundation
Las Vegas, Nevada, United States, 89135
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Apellis Pharmaceuticals, Inc.
Investigators
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Study Director: Federico Grossi, MD, PhD Apellis Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Apellis Pharmaceuticals, Inc.:
Study Protocol  [PDF] June 15, 2017
Statistical Analysis Plan  [PDF] June 7, 2018

More Information
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Responsible Party: Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02264639    
Other Study ID Numbers: APL-CP0514
First Posted: October 15, 2014    Key Record Dates
Results First Posted: January 8, 2021
Last Update Posted: January 8, 2021
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Apellis Pharmaceuticals, Inc.:
PNH
Paroxysmal Nocturnal Hemoglobinuria
Complement inhibitor
Anemia
Hemoglobinuria
 hematologic diseases
extravascular hemolysis (EVH)
intravascular hemolysis (IVH)
C3 inhibitor
Additional relevant MeSH terms:
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Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
 Male Urogenital Diseases
Urological Manifestations
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases