A Phase I Study to Assess the Safety of Pegcetacoplan (AP... | NCT02264639 | Trialant
NCT02264639
Sponsor
Apellis Pharmaceuticals, Inc.
Status
Completed
Last Update Posted
Jan 8, 2021Actual
Enrollment
9Actual
Phase
Phase 1
Conditions
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Interventions
Pegcetacoplan
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT02264639
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
APL-CP0514
Secondary IDs
Not provided
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).
Acronym
Not provided
Organization
Apellis Pharmaceuticals, Inc.INDUSTRY
Status Module
Record Verification Date
Dec 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
Not provided
Start Date
Feb 23, 2015Actual
Primary Completion Date
Oct 22, 2018Actual
Completion Date
Oct 22, 2018Actual
First Submitted Date
Oct 8, 2014
First Submission Date that Met QC Criteria
Oct 10, 2014
First Posted Date
Oct 15, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Jul 31, 2020
Results First Submitted that Met QC Criteria
Dec 14, 2020
Results First Posted Date
Jan 8, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Dec 14, 2020
Last Update Posted Date
Jan 8, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Apellis Pharmaceuticals, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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
Conditions Module
Conditions
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords
PNH
Paroxysmal Nocturnal Hemoglobinuria
Complement inhibitor
Anemia
Hemoglobinuria
hematologic diseases
extravascular hemolysis (EVH)
intravascular hemolysis (IVH)
C3 inhibitor
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
9Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1
Experimental
First Dose 25mg, Repeated Dose 5 mg/day
Drug: Pegcetacoplan
Cohort 2
Experimental
First Dose 50 mg, Repeated Dose 30 mg/day
Drug: Pegcetacoplan
Cohort 3
Experimental
Repeated Dose 180 mg/day
Drug: Pegcetacoplan
Cohort 4
Experimental
Repeated Dose 270 mg/day
Drug: Pegcetacoplan
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Pegcetacoplan
Drug
Complement (C3) Inhibitor
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
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).
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.
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 Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
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.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Federico Grossi, MD, PhD
Apellis Pharmaceuticals, Inc.
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
University of Southern California Norris Comprehensive Cancer Center
Los Angeles
California
90033
United States
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Subjects could participate in more than 1 cohort. Overall, 9 unique subjects were evaluated in 4 cohorts, with some subjects participating in >1 cohort. Single-dose phase: 4 unique subjects evaluated (2 each in Cohorts 1 and 2). Multiple-dose phase: 8 unique subjects evaluated, comprising 3 subjects who also participated in single-dose phase (1 in Cohort 1; 2 in Cohort 2) plus a further 5 unique subjects. Each cohort included a 30-day screening phase prior to treatment with pegcetacoplan.
Recruitment Details
Paroxysmal nocturnal hemoglobinuria (PNH) subjects who were still anemic during treatment with eculizumab (Soliris®) were enrolled in this Phase 1, open-label, single- and multiple-ascending dose study to receive treatment with pegcetacoplan (APL-2) as an add-on to standard of care treatment. The study was conducted at 7 sites in the United States.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohort 1 Single- and Multiple-dose Phase
Cohort 1 single-dose phase: Subjects received a single subcutaneous (SC) dose of 25 milligrams (mg) pegcetacoplan on Day 1.
Cohort 1 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 5 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jun 15, 2017
Jul 28, 2020
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
APL-2
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.
Lakes Research
Miami Lakes
Florida
33014
United States
University of Lousiville
Louisville
Kentucky
40202
United States
John Hopkins Hospital
Baltimore
Maryland
21231
United States
Cure 4 The Kids Foundation
Las Vegas
Nevada
89135
United States
Duke University Medical Center
Durham
North Carolina
27710
United States
Cleveland Clinic
Cleveland
Ohio
44195
United States
FG001
Cohort 2 Single- and Multiple-dose Phase
Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).
FG002
Cohort 2 Single-dose Phase, Then Cohorts 2, 3, and 4 Multiple-dose Phase
Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).
Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
FG003
Cohorts 3 and 4 Multiple-dose Phase
Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
FG004
Cohort 4 Multiple-dose Phase
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
FG0002 subjectsSubjects in this arm participated in Cohort 1 only.
FG0011 subjectsSubject in this arm participated in Cohort 2 only.
FG0021 subjectsSubject in this arm participated in Cohorts 2, 3 and 4.
FG0031 subjectsSubject in this arm participated in Cohorts 3 and 4; single-dose phase was not applicable.
FG0044 subjectsSubjects in this arm participated in Cohort 4 only; single-dose phase was not applicable.
COMPLETED
Completed the study (with reference to the last cohort in which a subject participated).
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG0043 subjects
NOT COMPLETED
FG0002 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0041 subjects
Type
Comment
Reasons
Death (after completing single-dose phase)
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Withdrawal by subject (during multiple-dose phase)
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Pregnancy (during multiple-dose phase)
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Major Intercurrent Illness (during multiple-dose phase)
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
The safety population included all enrolled subjects who received at least 1 dose of study drug. Total unique participants = 9. Subjects could participate in more than 1 cohort. 1 subject participated in Cohorts 2, 3 and 4, and 1 subject participated in Cohorts 3 and 4.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1 Single- and Multiple-dose Phase
Cohort 1 single-dose phase: Subjects received a single SC dose of 25 mg pegcetacoplan on Day 1.
Cohort 1 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 5 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).
BG001
Cohort 2 Single- and Multiple-dose Phase
Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).
BG002
Cohort 2 Single-dose Phase, Then Cohorts 2, 3, and 4 Multiple-dose Phase
Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).
Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
BG003
Cohorts 3 and 4 Multiple-dose Phase
Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
BG004
Cohort 4 Multiple-dose Phase
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0002
BG0011
BG0021
BG0031
BG0044
BG0059
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG0010
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
United States
Title
Measurements
BG0002
BG0011
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
The safety population included all enrolled subjects who received at least 1 dose of study drug.
Posted
Count of Participants
Participants
From single dose of study drug (Day 1) up to 30 days
ID
Title
Description
OG000
Cohort 1 Single-dose Phase
Subjects received a single SC dose of 25 mg pegcetacoplan on Day 1.
OG001
Cohort 2 Single-dose Phase
Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.
Units
Counts
Participants
OG0002
OG0012
Title
Denominators
Categories
Any TEAE
Title
Measurements
OG0001
OG0012
TEAE at least possibly related to study drug
Title
Measurements
OG000
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.
The safety population included all enrolled subjects who received at least 1 dose of study drug.
Posted
Count of Participants
Participants
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).
ID
Title
Description
OG000
Cohort 1 Multiple-dose Phase
Subjects received 5 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).
OG001
Cohort 2 Multiple-dose Phase
Subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).
OG002
Cohort 3 Multiple-dose Phase
Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).
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.
The PK population was defined as all subjects in the safety population who had at least 1 PK sample drawn with a measurable serum concentration. Results were reported for Cohort 4 only. Due to the small sample size in Cohorts 1 through 3, summaries for continuous data using descriptive statistics were not performed.
Posted
Mean
Standard Deviation
micrograms*hour/milliliter (μg*hour/mL)
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.
ID
Title
Description
OG000
Cohort 4 Multiple-dose Phase
Subjects received 270 mg/day SC dose of pegcetacoplan for up to 729 days (from Day 1 up to Day 729).
After Day 28, individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
Units
Counts
Participants
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.
The PK population was defined as all subjects in the safety population who had at least 1 PK sample drawn with a measurable serum concentration. Results were reported for Cohort 4 only. Due to the small sample size in Cohorts 1 through 3, summaries for continuous data using descriptive statistics were not performed.
Posted
Mean
Standard Deviation
μg/mL
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.
ID
Title
Description
OG000
Cohort 4 Multiple-dose Phase
Subjects received 270 mg/day SC dose of pegcetacoplan for up to 729 days (from Day 1 up to Day 729).
After Day 28, individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
Units
Counts
Time Frame
TEAE data is reported from first dose of study drug up to 30 days after last dose of study drug (Cohorts 1 and 2, single-dose phase: up to 30 days; Cohorts 1-3, multiple-dose phase: up to 58 days; Cohort 4, multiple-dose phase: up to 759 days).
Description
The safety population included all enrolled subjects who received at least 1 dose of study drug. The 4 cohorts of 12 subjects overall represents 9 unique participants. Subjects could participate in more than 1 cohort. The all-cause mortality table includes the death of 1 subject in Cohort 1, resulting from a serious AE which was not treatment-emergent.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohort 1 Single-dose Phase
Subjects received a single SC dose of 25 mg pegcetacoplan on Day 1.
1
2
0
2
1
2
EG001
Cohort 2 Single-dose Phase
Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.
0
2
0
2
2
2
EG002
Cohort 1 Multiple-dose Phase
Subjects received pegcetacoplan 5 mg/day as SC dose for 28 days (from Day 29 to Day 56).
0
1
0
1
1
1
EG003
Cohort 2 Multiple-dose Phase
Subjects received pegcetacoplan 30 mg/day as SC dose for 28 days (from Day 29 to Day 56).
0
2
0
2
2
2
EG004
Cohort 3 Multiple-dose Phase
Subjects received pegcetacoplan 180 mg/day as SC dose for 28 days (from Day 1 to Day 28).
0
2
0
2
1
2
EG005
Cohort 4 Multiple-dose Phase
Subjects received pegcetacoplan 270 mg/day as SC dose for up to 729 days (from Day 1 up to Day 729).
After Day 28, individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
Female Urogenital Diseases and Pregnancy Complications
D000091642
Urogenital Diseases
D052801
Male Urogenital Diseases
D020924
Urological Manifestations
D012816
Signs and Symptoms
D013568
Pathological Conditions, Signs and Symptoms
D010335
Pathologic Processes
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C000716074
pegcetacoplan
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
FG004
0 subjects
0 subjects
FG004
1 subjects
0
BG0040
BG0050
Between 18 and 65 years
BG0001
BG0011
BG0021
BG0031
BG0044
BG0058
>=65 years
BG0001
BG0010
BG0020
BG0030
BG0040
BG0051
1
BG0031
BG0044
BG0058
Male
BG0000
BG0011
BG0020
BG0030
BG0040
BG0051
0
BG0031
BG0040
BG0051
Not Hispanic or Latino
BG0002
BG0011
BG0021
BG0030
BG0044
BG0058
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
0
BG0030
BG0040
BG0050
Asian
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
Black or African American
BG0000
BG0010
BG0020
BG0030
BG0041
BG0051
White
BG0002
BG0011
BG0021
BG0031
BG0043
BG0058
More than one race
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
1
BG0031
BG0044
BG0059
0
OG0011
Serious TEAE
Title
Measurements
OG0000
OG0010
TEAE leading to study drug discontinuation
Title
Measurements
OG0000
OG0010
TEAE leading to death
Title
Measurements
OG0000
OG0010
Maximum severity of all TEAEs: mild
Title
Measurements
OG0000
OG0011
Maximum severity of all TEAEs: moderate
Title
Measurements
OG0001
OG0011
Maximum severity of all TEAEs: severe
Title
Measurements
OG0000
OG0010
OG003
Cohort 4 Multiple-dose Phase
Subjects received 270 mg/day SC dose of pegcetacoplan for up to 729 days (from Day 1 up to Day 729).
After Day 28, individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.
Units
Counts
Participants
OG0001
OG0012
OG0022
OG0036
Title
Denominators
Categories
Any TEAE
Title
Measurements
OG0001
OG0012
OG0021
OG0036
TEAE at least possibly related to study drug
Title
Measurements
OG0000
OG0011
OG0021
OG003
Serious TEAE
Title
Measurements
OG0000
OG0010
OG0020
OG003
TEAE leading to study drug discontinuation
Title
Measurements
OG0001
OG0010
OG0020
OG003
TEAE leading to death
Title
Measurements
OG0000
OG0010
OG0020
OG003
Maximum severity of all TEAEs: mild
Title
Measurements
OG0000
OG0010
OG0021
OG003
Maximum severity of all TEAEs: moderate
Title
Measurements
OG0000
OG0012
OG0020
OG003
Maximum severity of all TEAEs: severe
Title
Measurements
OG0001
OG0010
OG0020
OG003
Maximum severity of all TEAEs: life-threatening
Title
Measurements
OG0000
OG0010
OG0020
OG003
OG0006
Title
Denominators
Categories
Title
Measurements
OG0006,500,000± 3,990,000
Participants
OG0006
Title
Denominators
Categories
270 mg Dose
ParticipantsOG0006
Title
Measurements
OG000627± 207
360 mg Dose
ParticipantsOG0004
Title
Measurements
OG000543± 192
440 mg Dose
ParticipantsOG0001
Title
Measurements
OG000624± NANo standard deviation is presented since mean value is derived from a single subject.