Back to resultsA Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH
Primary Purpose
PNH
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pegcetacoplan
Sponsored by
About this trial
This is an interventional treatment trial for PNH focused on measuring PNH, Paroxysmal Nocturnal Hemoglobinuria, Complement inhibitor, Anemia, Hemoglobinuria, Hemolysis, Hematologic diseases, Extravascular hemolysis (EVH), Intravascular hemolysis (IVH), C3 inhibitor
Eligibility Criteria
Inclusion Criteria:
- At least 18 years old (inclusive)
- Diagnosed with PNH (white blood cell (WBC) clone >10%)
- Lactose dehydrogenase (LD) ≥2 times the upper limit of normal
- Screening Ferritin ≥ normal and Total Iron Binding Capacity (TIBC) < LLN based on central lab reference ranges. If a subject is receiving iron supplements at screening, the investigator must ensure that his/her dose has been stable for 8 weeks prior to enrolment and must be maintained throughout the study
- Last transfusion within 12 months prior to screening
- Platelet count of >30,000/mm3 at the screening visit
- Absolute neutrophil count >500/ mm3 at the screening visit
- 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
- Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study
- Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with pegcetacoplan. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
- Willing and able to give informed consent
Exclusion Criteria:
- Prior eculizumab (Soliris®) treatment
- Active bacterial infection
- Hereditary complement deficiency
- History of bone marrow transplantation
- Concurrent severe aplastic anemia (SAA), defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or anti-thymocyte globulin
- Participation in any other investigational drug trial or exposure to another 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
- Breast-feeding women
- History of meningococcal disease
Sites / Locations
- Acibadem City Clinic MHAT Tokuda EAD Sofia
- Specialized Hospital for Active Treatment of Hematologic Diseases EAD, Sofia
- Klinički centar Srbije
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental: Cohort 1
Arm Description
270 mg/day (up to 360 mg/day from Day 29) from Day 1 to Day 364*
Outcomes
Primary Outcome Measures
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity
TEAEs were defined as adverse events (AE) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE was defined as a TEAE with a relationship to study drug of possible, probable, or definite. TEAEs were graded according to the Common Terminology Criteria for Adverse Events (v4.03) based on: Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening, Grade 5: Death related to AE.
Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level
Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Mean Change From Baseline in Haptoglobin Level
Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Mean Change From Baseline in Hemoglobin (Hb) Level
Hematology assessments of Hb were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Secondary Outcome Measures
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
The FACIT-Fatigue scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. Higher score corresponds to a higher quality of life (QoL).
Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level
Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Mean Change From Baseline in Total Bilirubin Level
Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Mean Number of Red Blood Cell (RBC) Transfusions Per Month
The number of on-study RBC transfusions was monitored throughout the treatment period.
Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL
The LASA consists of 3 items, where the respondents were asked to rate their perceived level of functioning. Specific domains included activity level, ability to carry out daily activities, and an item for overall QoL. Their level of functioning was reported on a 0 to 100 scale with 0 indicates "As low as could be" and 100 indicates "As high as could be". The combined score ranged from 0 to 300, with higher scores corresponding to a higher QoL.
Mean Serum Concentrations of Pegcetacoplan
Serum concentrations of pegcetacoplan at Day 365 are presented.
Mean Area Under the Serum Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration at the End of the Study (AUCtotal)
The AUCtotal of pegcetacoplan was estimated using a non-compartmental approach.
Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total)
The Ctrough,max,total of pegcetacoplan was estimated using a non-compartmental approach.
Full Information
NCT ID
NCT03593200
First Posted
June 28, 2018
Last Updated
December 21, 2020
Sponsor
Apellis Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03593200
Brief Title
A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH
Official Title
Phase IIa, Open Label, Multiple Dose Study to Assess the Safety, Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 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
August 16, 2018 (Actual)
Primary Completion Date
October 22, 2019 (Actual)
Study Completion Date
October 22, 2019 (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 is a Phase IIa, open-label, multiple dose, study in patients with PNH who have not received eculizumab (Soliris ®) in the past. A single cohort of subjects is planned for evaluation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PNH
Keywords
PNH, Paroxysmal Nocturnal Hemoglobinuria, Complement inhibitor, Anemia, Hemoglobinuria, Hemolysis, Hematologic diseases, Extravascular hemolysis (EVH), Intravascular hemolysis (IVH), C3 inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental: Cohort 1
Arm Type
Experimental
Arm Description
270 mg/day (up to 360 mg/day from Day 29) from Day 1 to Day 364*
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
Description
TEAEs were defined as adverse events (AE) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE was defined as a TEAE with a relationship to study drug of possible, probable, or definite. TEAEs were graded according to the Common Terminology Criteria for Adverse Events (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 Day 1 to 30 days after the last dose (approximately 56 weeks)
Title
Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level
Description
Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame
Baseline and Day 365
Title
Mean Change From Baseline in Haptoglobin Level
Description
Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame
Baseline and Day 365
Title
Mean Change From Baseline in Hemoglobin (Hb) Level
Description
Hematology assessments of Hb were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame
Baseline and Day 365
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
Description
The FACIT-Fatigue scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. Higher score corresponds to a higher quality of life (QoL).
Time Frame
Baseline and Day 365
Title
Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level
Description
Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame
Baseline and Day 365
Title
Mean Change From Baseline in Total Bilirubin Level
Description
Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame
Baseline and Day 365
Title
Mean Number of Red Blood Cell (RBC) Transfusions Per Month
Description
The number of on-study RBC transfusions was monitored throughout the treatment period.
Time Frame
From Day 1 to Day 364
Title
Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL
Description
The LASA consists of 3 items, where the respondents were asked to rate their perceived level of functioning. Specific domains included activity level, ability to carry out daily activities, and an item for overall QoL. Their level of functioning was reported on a 0 to 100 scale with 0 indicates "As low as could be" and 100 indicates "As high as could be". The combined score ranged from 0 to 300, with higher scores corresponding to a higher QoL.
Time Frame
Baseline and Day 365
Title
Mean Serum Concentrations of Pegcetacoplan
Description
Serum concentrations of pegcetacoplan at Day 365 are presented.
Time Frame
Day 365
Title
Mean Area Under the Serum Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration at the End of the Study (AUCtotal)
Description
The AUCtotal of pegcetacoplan was estimated using a non-compartmental approach.
Time Frame
Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.
Title
Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total)
Description
The Ctrough,max,total of pegcetacoplan was estimated using a non-compartmental approach.
Time Frame
Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
At least 18 years old (inclusive)
Diagnosed with PNH (white blood cell (WBC) clone >10%)
Lactose dehydrogenase (LD) ≥2 times the upper limit of normal
Screening Ferritin ≥ normal and Total Iron Binding Capacity (TIBC) < LLN based on central lab reference ranges. If a subject is receiving iron supplements at screening, the investigator must ensure that his/her dose has been stable for 8 weeks prior to enrolment and must be maintained throughout the study
Last transfusion within 12 months prior to screening
Platelet count of >30,000/mm3 at the screening visit
Absolute neutrophil count >500/ mm3 at the screening visit
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
Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study
Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with pegcetacoplan. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
Willing and able to give informed consent
Exclusion Criteria:
Prior eculizumab (Soliris®) treatment
Active bacterial infection
Hereditary complement deficiency
History of bone marrow transplantation
Concurrent severe aplastic anemia (SAA), defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or anti-thymocyte globulin
Participation in any other investigational drug trial or exposure to another 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
Breast-feeding women
History of meningococcal disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Federico Grossi, MD, PhD
Organizational Affiliation
Study Director
Official's Role
Study Director
Facility Information:
Facility Name
Acibadem City Clinic MHAT Tokuda EAD Sofia
City
Sofia
Country
Bulgaria
Facility Name
Specialized Hospital for Active Treatment of Hematologic Diseases EAD, Sofia
City
Sofia
Country
Bulgaria
Facility Name
Klinički centar Srbije
City
Belgrade
Country
Serbia
12. IPD Sharing Statement
Citations:
PubMed Identifier
35869170
Citation
Wong RSM, Pullon HWH, Amine I, Bogdanovic A, Deschatelets P, Francois CG, Ignatova K, Issaragrisil S, Niparuck P, Numbenjapon T, Roman E, Sathar J, Xu R, Al-Adhami M, Tan L, Tse E, Grossi FV. Inhibition of C3 with pegcetacoplan results in normalization of hemolysis markers in paroxysmal nocturnal hemoglobinuria. Ann Hematol. 2022 Sep;101(9):1971-1986. doi: 10.1007/s00277-022-04903-x. Epub 2022 Jul 22.
Results Reference
derived
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A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH
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