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    Clinical Trial Results:
    A Phase 3, Randomized, Placebo-Controlled, Double-Blinded, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients with C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis

    Summary
    EudraCT number
    		 2020-003767-25
    Trial protocol
    		 DE   NL   CZ   BE   AT   FR   PL   IT   ES  
    Global end of trial date
    14 Jan 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 Jul 2025
    First version publication date
    27 Jul 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    APL2-C3G-310
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05067127
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Apellis Pharmaceuticals, Inc
    Sponsor organisation address
    100 5th Ave, Waltham, Massachusetts, United States, 02451
    Public contact
    Apellis Clinical Trial Information Line, Apellis Pharmaceuticals, Inc, +1 833-284-6361, clinicaltrials@apellis.com
    Scientific contact
    Apellis Clinical Trial Information Line, Apellis Pharmaceuticals, Inc, +1 833-284-6361, clinicaltrials@apellis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002600-PIP04-22
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Jan 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Jan 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the efficacy of twice weekly subcutaneous (SC) doses of pegcetacoplan compared with that of placebo in subjects with primary complement 3 glomerulopathy (C3G) or immune-complex membranoproliferative glomerulonephritis (IC-MPGN) on the basis of a reduction in proteinuria.
    Protection of trial subjects
    This research was carried out in accordance with the protocol, applicable regulations, the ethical principles set forth in the Declaration of Helsinki, and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Harmonised Guideline for Good Clinical Practice E6 Revision 2. An external, independent data monitoring committee assessed the safety and tolerability data of the study periodically.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 May 2022
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Australia: 4
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Brazil: 19
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Czechia: 1
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Israel: 1
    Country: Number of subjects enrolled
    Italy: 17
    Country: Number of subjects enrolled
    Japan: 3
    Country: Number of subjects enrolled
    Korea, Republic of: 4
    Country: Number of subjects enrolled
    Netherlands: 7
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    Switzerland: 3
    Country: Number of subjects enrolled
    United Kingdom: 9
    Country: Number of subjects enrolled
    United States: 31
    Worldwide total number of subjects
    124
    EEA total number of subjects
    44
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    55
    Adults (18-64 years)
    67
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This Phase 3 randomized, placebo-controlled, double-blinded study was conducted in subjects with C3G or primary IC-MPGN at 122 sites.

    Pre-assignment
    Screening details
    		 This study consisted of a screening period (10 weeks), 26-week randomized controlled period (RCP), followed by a 26-week open-label period (OLP) and follow-up period (8 weeks). Subjects were randomized to receive pegcetacoplan or placebo in a ratio of 1:1 in RCP. A total of 124 subjects were enrolled in this study.

    Period 1
    Period 1 title
    Randomized Controlled Period (26 Weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Randomized Controlled Period: Pegcetacoplan
    Arm description
    		 All adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kilogram (kg) received pegcetacoplan 1080 milligram (mg) subcutaneous (SC) infusion twice weekly for 26 weeks in RCP. Adolescent subjects with body weight 35 to <50 kg received pegcetacoplan 648 mg for the first SC infusion and 810 mg SC infusion thereafter twice weekly for 26 weeks in RCP. Adolescent subjects with body weight 30 to <35 kg received pegcetacoplan 540 mg for the first 2 SC infusions and 648 mg SC infusion thereafter twice weekly for 26 weeks in RCP.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pegcetacoplan
    Investigational medicinal product code
    APL-2
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Pegcetacoplan SC infusion twice weekly for 26 weeks in RCP.

    Arm title
    		 Randomized Controlled Period: Placebo
    Arm description
    		 All adult subjects (regardless of weight) and adolescent subjects (with body weight: 30 to <35 kg, 35 to <50 kg, and >=50 kg) received placebo matching with pegcetacoplan SC infusion twice weekly for 26 weeks in RCP.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matching with pegcetacoplan SC infusion twice weekly for 26 weeks in RCP.

    Number of subjects in period 1
    		Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Started
    63
    61
    Completed
    61
    57
    Not completed
    2
    4
         Consent withdrawn by subject
    -
    2
         Investigator or Medical Monitor Decision
    1
    -
         Death
    1
    -
         Pregnancy
    -
    1
         Lost to follow-up
    -
    1
    Period 2
    Period 2 title
    Open-Label Period (26 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Open-Label Period: Pegcetacoplan to Pegcetacoplan
    Arm description
    		 All eligible adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kg who received pegcetacoplan in RCP continued to receive pegcetacoplan 1080 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 35 to <50 kg who received pegcetacoplan in RCP continued to receive pegcetacoplan 810 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 30 to <35 kg who received pegcetacoplan in RCP continued to receive pegcetacoplan 648 mg SC infusion twice weekly for 26 weeks in OLP.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pegcetacoplan
    Investigational medicinal product code
    APL-2
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Pegcetacoplan SC infusion twice weekly for 26 weeks in OLP.

    Arm title
    		 Open-Label Period: Placebo to Pegcetacoplan
    Arm description
    		 All eligible adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kg who received placebo in RCP entered OLP to receive pegcetacoplan 1080 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 35 to <50 kg who received placebo in RCP entered OLP to receive pegcetacoplan 810 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 30 to <35 kg who received placebo in RCP entered OLP to receive pegcetacoplan 648 mg SC infusion twice weekly for 26 weeks in OLP.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matching with pegcetacoplan SC infusion twice weekly for 26 weeks in OLP.

    Number of subjects in period 2
    		Open-Label Period: Pegcetacoplan to Pegcetacoplan Open-Label Period: Placebo to Pegcetacoplan
    Started
    61
    57
    Completed
    59
    55
    Not completed
    2
    2
         Consent withdrawn by subject
    -
    1
         Investigator or Medical Monitor Decision
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Randomized Controlled Period: Pegcetacoplan
    Reporting group description
    		 All adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kilogram (kg) received pegcetacoplan 1080 milligram (mg) subcutaneous (SC) infusion twice weekly for 26 weeks in RCP. Adolescent subjects with body weight 35 to <50 kg received pegcetacoplan 648 mg for the first SC infusion and 810 mg SC infusion thereafter twice weekly for 26 weeks in RCP. Adolescent subjects with body weight 30 to <35 kg received pegcetacoplan 540 mg for the first 2 SC infusions and 648 mg SC infusion thereafter twice weekly for 26 weeks in RCP.

    Reporting group title
    Randomized Controlled Period: Placebo
    Reporting group description
    		 All adult subjects (regardless of weight) and adolescent subjects (with body weight: 30 to <35 kg, 35 to <50 kg, and >=50 kg) received placebo matching with pegcetacoplan SC infusion twice weekly for 26 weeks in RCP.

    Reporting group values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo Total
    Number of subjects
    		 63 61 124
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 28.2 ( 17.08 ) 23.6 ( 14.26 ) -
    Gender categorical
    Units: Subjects
        Female
    		 37 33 70
        Male
    		 26 28 54
    Race
    Units: Subjects
        American Indian or Alaskan Native
    		 1 0 1
        Asian
    		 9 9 18
        Black or African American
    		 1 0 1
        White
    		 45 46 91
        Other
    		 7 6 13
    Ethnicity
    Units: Subjects
        Hispanic
    		 15 10 25
        Not Hispanic or Latino
    		 41 47 88
        Not Reported
    		 6 2 8
        Unknown
    		 1 2 3

    End points

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    End points reporting groups
    Reporting group title
    Randomized Controlled Period: Pegcetacoplan
    Reporting group description
    		 All adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kilogram (kg) received pegcetacoplan 1080 milligram (mg) subcutaneous (SC) infusion twice weekly for 26 weeks in RCP. Adolescent subjects with body weight 35 to <50 kg received pegcetacoplan 648 mg for the first SC infusion and 810 mg SC infusion thereafter twice weekly for 26 weeks in RCP. Adolescent subjects with body weight 30 to <35 kg received pegcetacoplan 540 mg for the first 2 SC infusions and 648 mg SC infusion thereafter twice weekly for 26 weeks in RCP.

    Reporting group title
    Randomized Controlled Period: Placebo
    Reporting group description
    		 All adult subjects (regardless of weight) and adolescent subjects (with body weight: 30 to <35 kg, 35 to <50 kg, and >=50 kg) received placebo matching with pegcetacoplan SC infusion twice weekly for 26 weeks in RCP.
    Reporting group title
    Open-Label Period: Pegcetacoplan to Pegcetacoplan
    Reporting group description
    		 All eligible adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kg who received pegcetacoplan in RCP continued to receive pegcetacoplan 1080 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 35 to <50 kg who received pegcetacoplan in RCP continued to receive pegcetacoplan 810 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 30 to <35 kg who received pegcetacoplan in RCP continued to receive pegcetacoplan 648 mg SC infusion twice weekly for 26 weeks in OLP.

    Reporting group title
    Open-Label Period: Placebo to Pegcetacoplan
    Reporting group description
    		 All eligible adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kg who received placebo in RCP entered OLP to receive pegcetacoplan 1080 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 35 to <50 kg who received placebo in RCP entered OLP to receive pegcetacoplan 810 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 30 to <35 kg who received placebo in RCP entered OLP to receive pegcetacoplan 648 mg SC infusion twice weekly for 26 weeks in OLP.

    Primary: Randomized Controlled Period: Change From Baseline in Log-Transformed Urine Protein-to-Creatinine Ratio (uPCR) at Week 26

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    End point title
    		 Randomized Controlled Period: Change From Baseline in Log-Transformed Urine Protein-to-Creatinine Ratio (uPCR) at Week 26
    End point description
    Baseline uPCR value was calculated as the average of the uPCR measurements from at least 6 of the 9 first-morning spot urine (FMU) samples collected between the start of screening and Day 1, inclusive. The uPCR values used to calculate baseline included those from the samples collected on Day −2, Day −1, and before dosing on Day 1. In situations where less than 6 samples or more than 9 samples were collected, the average of all collected samples was used for baseline derivation. The difference between treatment groups using a composite contrast of equal-weighted average over Weeks 24, 25, and 26 was estimated. The intent-to-treat (ITT) analysis set included all randomized subjects.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) to Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    63
    61
    Units: ratio
        least squares mean (confidence interval 95%)
    -1.114 (-1.380 to -0.848)
    0.029 (-0.090 to 0.148)
    Statistical analysis title
    		 Treatment difference in log-transformed uPCR
    Statistical analysis description
    An mixed-effect model for repeated measures (MMRM) included fixed categorical effect for treatment group, visit, disease type, baseline immunosuppressants use, stratification factors, and the visit-by-treatment group interactions as well as the continuous, fixed covariate of baseline log-transformed uPCR, was utilized to analyze the log-transformed ratio of uPCR at Week 26 compared to baseline.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 MMRM
    Parameter type
    		 Difference in LS mean
    Point estimate
    -1.143
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.436
         upper limit
    		 -0.85

    Secondary: Randomized Controlled Period: Percentage of Subjects Who Achieved the Composite Renal Endpoint at Week 26

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    End point title
    		 Randomized Controlled Period: Percentage of Subjects Who Achieved the Composite Renal Endpoint at Week 26
    End point description
    Subject who achieved a composite renal endpoint was defined as: (1) a stable or improved estimated glomerular filtration rate (eGFR) compared to baseline (<=15% reduction in eGFR), and (2) a >=50% reduction in uPCR compared to baseline. Percentages are rounded off to the hundredth decimal place. The ITT analysis set included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    63
    61
    Units: percentage of subjects
        number (not applicable)
    49.21
    3.28
    Statistical analysis title
    		 Treatment difference in composite renal endpoint
    Statistical analysis description
    The logistic model included treatment group as independent variable and adjusted for baseline eGFR values, baseline log-transformed uPCR values, disease type, and stratification factors.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    27.516
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.105
         upper limit
    		 124.026

    Secondary: Randomized Controlled Period: Percentage of Subjects With a Reduction of At Least 50% From Baseline in Urine Protein-to-Creatinine Ratio at Week 26

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    End point title
    		 Randomized Controlled Period: Percentage of Subjects With a Reduction of At Least 50% From Baseline in Urine Protein-to-Creatinine Ratio at Week 26
    End point description
    Baseline uPCR value was calculated as the average of the uPCR measurements from at least 6 of the 9 FMU samples collected between the start of screening and Day 1, inclusive. The uPCR values used to calculate baseline included those from the samples collected on Day −2, Day −1, and before dosing on Day 1. In situations where less than 6 samples or more than 9 samples were collected, the average of all collected samples was used for baseline derivation. Percentages are rounded off to the hundredth decimal place. The ITT analysis set included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    63
    61
    Units: percentage of subjects
        number (not applicable)
    60.32
    4.92
    Statistical analysis title
    		 Treatment difference in 50% reduction in uPCR
    Statistical analysis description
    The logistic model included treatment group as independent variable and adjusted for baseline log-transformed uPCR values, disease type, and stratification factors.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    30.932
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.401
         upper limit
    		 113.897

    Secondary: Randomized Controlled Period: Change From Baseline in the C3 Glomerulopathy (C3G) Histologic Index Activity Score at Week 26

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    End point title
    		 Randomized Controlled Period: Change From Baseline in the C3 Glomerulopathy (C3G) Histologic Index Activity Score at Week 26
    End point description
    The C3G histologic index used to assess disease activity and chronicity in C3G. The C3G total activity score ranges from 0 (worse) to 21 (best). Higher scores indicate better outcome. Baseline was defined as the most recent non-missing measurement prior to taking the first dose of study drug. The ITT analysis set included all randomized subjects. Since adolescents subjects were not required to provide post-screening biopsies, this endpoint was analyzed based on adult subjects only.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    35
    34
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -3.482 (-4.721 to -2.244)
    -2.480 (-3.775 to -1.186)
    Statistical analysis title
    		 Treatment difference in C3G histologic index
    Statistical analysis description
    Analysis of covariance (ANCOVA) model included treatment as fixed effect, adjusted for baseline C3G histologic index activity score, disease type, and stratification factors.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2753
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -1.002
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.803
         upper limit
    		 0.798

    Secondary: Randomized Controlled Period: Percentage of Subjects Who Showed Decrease in C3c Staining on Renal Biopsy From Baseline at Week 26

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    End point title
    		 Randomized Controlled Period: Percentage of Subjects Who Showed Decrease in C3c Staining on Renal Biopsy From Baseline at Week 26
    End point description
    Subject who showed decrease in C3c staining was defined as decrease of at least 2 orders of magnitude of intensity from baseline. Percentages are rounded off to the hundredth decimal place. The ITT analysis set included all randomized subjects. Since adolescents subjects were not required to provide post-screening biopsies, this endpoint was analyzed based on adult subjects only.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    35
    34
    Units: percentage of subjects
        number (not applicable)
    74.29
    11.76
    Statistical analysis title
    		 Treatment difference in C3c staining
    Statistical analysis description
    The logistic model included treatment group as independent variable and adjusted for baseline C3c staining, disease type, and stratification factors.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    27.392
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.477
         upper limit
    		 115.852

    Secondary: Randomized Controlled Period: Change From Baseline in Estimated Glomerular Filtration Rate at Week 26

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    End point title
    		 Randomized Controlled Period: Change From Baseline in Estimated Glomerular Filtration Rate at Week 26
    End point description
    Serum samples were collected to determine the eGFR, calculated by using chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation for adults and the Bedside Schwartz equation for adolescents. Baseline eGFR value was calculated using the last non-missing assessment prior to first dose of study drug. The ITT analysis set included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    63
    61
    Units: milliliter (mL)/minute/1.73 meter square
        least squares mean (confidence interval 95%)
    -1.497 (-5.892 to 2.899)
    -7.808 (-11.570 to -4.047)
    Statistical analysis title
    		 Treatment difference in eGFR
    Statistical analysis description
    An MMRM model included fixed categorical effect for treatment group, visit, disease type, stratification factors, and the visit-by-treatment group interactions as well as the continuous, fixed covariate of baseline eGFR, was utilized to analyze the mean change from baseline to Week 26 in eGFR.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0333
    Method
    		 MMRM
    Parameter type
    		 Difference in LS mean
    Point estimate
    6.312
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.501
         upper limit
    		 12.122

    Secondary: Randomized Controlled Period: Percentage of Subjects Who Achieved Proteinuria <1 Gram (g)/Day at Week 24

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    End point title
    		 Randomized Controlled Period: Percentage of Subjects Who Achieved Proteinuria <1 Gram (g)/Day at Week 24
    End point description
    Urine samples were collected to determine the proteinuria. Percentage of subjects who achieved proteinuria <1 g/day was assessed by 24-hour urine protein. Percentages are rounded off to the hundredth decimal place. The ITT analysis set included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    63
    61
    Units: percentage of subjects
        number (not applicable)
    36.51
    11.48
    Statistical analysis title
    		 Treatment difference in proteinuria <1 g/day
    Statistical analysis description
    The logistic model included treatment group as independent variable and adjusted for baseline proteinuria values, disease type, and stratification factors.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0006
    Method
    		 Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5.753
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.106
         upper limit
    		 15.716

    Secondary: Randomized Controlled Period: Percentage of Subjects With Normalization of Serum Albumin Levels at Week 26

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    End point title
    		 Randomized Controlled Period: Percentage of Subjects With Normalization of Serum Albumin Levels at Week 26
    End point description
    Baseline serum albumin value was calculated as the average of up to 2 serum albumin measurements preceding and including Day 1. Week 26 serum albumin values was calculated as the average of up to 2 serum albumin measurements preceding and including Week 26, no earlier than Week 20 measurement. Percentages are rounded off to the hundredth decimal place. The ITT analysis set included all randomized subjects. Only subjects with serum albumin levels below lower limit of normal (LLN) at baseline are analyzed.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    27
    23
    Units: percentage of subjects
        number (not applicable)
    77.78
    4.35
    Statistical analysis title
    		 Treatment difference in serum albumin levels
    Statistical analysis description
    The logistic model included treatment group as independent variable and adjusted for baseline albumin values, disease type, and stratification factors.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    50
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    88.341
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.863
         upper limit
    		 880.544

    Secondary: Randomized Controlled Period: Percentage of Subjects With Serum C3 Levels Above the Lower Limit of Normal at Week 26

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    End point title
    		 Randomized Controlled Period: Percentage of Subjects With Serum C3 Levels Above the Lower Limit of Normal at Week 26
    End point description
    Baseline serum C3 value was calculated as the average of up to 2 serum C3 measurements preceding and including Day 1. Week 26 serum C3 value was calculated as the average of up to 2 serum C3 measurements preceding and including Week 26, no earlier than Week 20 measurement. Percentages are rounded off to the hundredth decimal place. The ITT analysis set included all randomized subjects. Only subjects with serum C3 levels below LLN at baseline are analyzed.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    41
    49
    Units: percentage of subjects
        number (not applicable)
    90.24
    6.12
    Statistical analysis title
    		 Treatment difference in serum C3 levels
    Statistical analysis description
    The logistic model included treatment group as independent variable and adjusted for baseline C3 levels, stratification factors and disease type.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0094
    Method
    		 Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    999.999
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.175
         upper limit
    		 9999.999

    Secondary: Randomized Controlled Period: Change From Baseline in the Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-Fatigue) Score at Week 26

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    End point title
    		 Randomized Controlled Period: Change From Baseline in the Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-Fatigue) Score at Week 26
    End point description
    The FACIT-Fatigue scale was a 13-item Likert scaled instrument that was self-administered by subjects. Subjects were presented with 13 statements and asked to indicate their responses 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 has a range of 0 (worse health-related quality of life) to 52 (best health-related quality of life). Higher scores indicate better quality of life. Baseline was defined as the most recent non-missing measurement prior to taking the first dose of study drug. The ITT analysis set included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    63
    61
    Units: units on a scale
        least squares mean (confidence interval 95%)
    0.929 (-1.549 to 3.407)
    0.367 (-1.949 to 2.683)
    Statistical analysis title
    		 Treatment difference in FACIT-fatigue score
    Statistical analysis description
    The ANCOVA model included treatment as fixed effect, adjusted for baseline, disease type, and stratification factors.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7384
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.562
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.739
         upper limit
    		 3.863

    Secondary: Randomized Controlled Period: Change From Baseline in the Kidney Disease Quality of Life (KDQOL) Score at Week 26

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    End point title
    		 Randomized Controlled Period: Change From Baseline in the Kidney Disease Quality of Life (KDQOL) Score at Week 26
    End point description
    The KDQOL score was constructed as the KDQOL-36 Summary Score (KSS) by averaging the 24 items from Burden of Kidney Disease, Symptoms and Problems of Kidney Disease, and Effects of Kidney Disease on scale ranging from 0 (worse health-related quality of life) to 100 (best health-related quality of life). Higher scores indicate better quality of life. Baseline was defined as the most recent non-missing measurement prior to taking the first dose of study drug. The ITT analysis set included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 26
    End point values
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo
    Number of subjects analysed
    63
    61
    Units: units on a scale
        least squares mean (confidence interval 95%)
    0.757 (-2.385 to 3.900)
    -0.587 (-3.847 to 2.672)
    Statistical analysis title
    		 Treatment difference in KDQOL score
    Statistical analysis description
    The ANCOVA model included treatment as fixed effect, adjusted for baseline, disease type, and stratification factors.
    Comparison groups
    Randomized Controlled Period: Pegcetacoplan v Randomized Controlled Period: Placebo
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5648
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    1.345
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.237
         upper limit
    		 5.927

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    TEAE data is reported from first dose of study drug (Day 1) up to 56 days after the last dose of study drug (Week 52), up to 60 weeks. Deaths (all-cause): From first dose of study drug (Day 1) up to end of the study, approximately 137 weeks.
    Adverse event reporting additional description
    The safety set included all subjects who received at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Randomized Controlled Period: Pegcetacoplan
    Reporting group description
    		 All adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kg received pegcetacoplan 1080 mg SC infusion twice weekly for 26 weeks in RCP. Adolescent subjects with body weight 35 to <50 kg received pegcetacoplan 648 mg for the first SC infusion and 810 mg SC infusion thereafter twice weekly for 26 weeks in RCP. Adolescent subjects with body weight 30 to <35 kg received pegcetacoplan 540 mg for the first 2 SC infusions and 648 mg SC infusion thereafter twice weekly for 26 weeks in RCP.

    Reporting group title
    Randomized Controlled Period: Placebo
    Reporting group description
    		 All adult subjects (regardless of weight) and adolescent subjects (with body weight: 30 to <35 kg, 35 to <50 kg, and >=50 kg) received placebo matching with pegcetacoplan SC infusion twice weekly for 26 weeks in RCP.

    Reporting group title
    Open-Label Period: Pegcetacoplan to Pegcetacoplan
    Reporting group description
    		 All eligible adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kg who received pegcetacoplan in RCP continued to receive pegcetacoplan 1080 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 35 to <50 kg who received pegcetacoplan in RCP continued to receive pegcetacoplan 810 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 30 to <35 kg who received pegcetacoplan in RCP continued to receive pegcetacoplan 648 mg SC infusion twice weekly for 26 weeks in OLP.

    Reporting group title
    Open-Label Period: Placebo to Pegcetacoplan
    Reporting group description
    		 All eligible adult subjects (regardless of weight) and adolescent subjects with body weight >=50 kg who received placebo in RCP entered OLP to receive pegcetacoplan 1080 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 35 to <50 kg who received placebo in RCP entered OLP to receive pegcetacoplan 810 mg SC infusion twice weekly for 26 weeks in OLP. Eligible adolescent subjects with body weight 30 to <35 kg who received placebo in RCP entered OLP to receive pegcetacoplan 648 mg SC infusion twice weekly for 26 weeks in OLP.

    Serious adverse events
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo Open-Label Period: Pegcetacoplan to Pegcetacoplan Open-Label Period: Placebo to Pegcetacoplan
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 63 (9.52%)
    6 / 61 (9.84%)
    6 / 61 (9.84%)
    4 / 57 (7.02%)
         number of deaths (all causes)
    1
    0
    0
    0
         number of deaths resulting from adverse events
    1
    0
    0
    0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 61 (1.64%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Maternal exposure during pregnancy
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 61 (1.64%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shunt malfunction
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shunt thrombosis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive urgency
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 61 (1.64%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 61 (1.64%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 63 (1.59%)
    2 / 61 (3.28%)
    2 / 61 (3.28%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    End stage renal disease
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 61 (1.64%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 61 (1.64%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster meningoencephalitis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shunt infection
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 61 (1.64%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 61 (0.00%)
    1 / 61 (1.64%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Randomized Controlled Period: Pegcetacoplan Randomized Controlled Period: Placebo Open-Label Period: Pegcetacoplan to Pegcetacoplan Open-Label Period: Placebo to Pegcetacoplan
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    53 / 63 (84.13%)
    56 / 61 (91.80%)
    47 / 61 (77.05%)
    42 / 57 (73.68%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    4 / 63 (6.35%)
    1 / 61 (1.64%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences all number
    4
    2
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 63 (4.76%)
    5 / 61 (8.20%)
    6 / 61 (9.84%)
    2 / 57 (3.51%)
         occurrences all number
    5
    5
    6
    2
    Hypotension
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 61 (0.00%)
    0 / 61 (0.00%)
    3 / 57 (5.26%)
         occurrences all number
    2
    0
    0
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 63 (0.00%)
    6 / 61 (9.84%)
    3 / 61 (4.92%)
    0 / 57 (0.00%)
         occurrences all number
    0
    6
    3
    0
    Headache
         subjects affected / exposed
    8 / 63 (12.70%)
    11 / 61 (18.03%)
    4 / 61 (6.56%)
    7 / 57 (12.28%)
         occurrences all number
    20
    14
    7
    8
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 63 (0.00%)
    4 / 61 (6.56%)
    5 / 61 (8.20%)
    4 / 57 (7.02%)
         occurrences all number
    0
    4
    5
    4
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 63 (0.00%)
    4 / 61 (6.56%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences all number
    0
    4
    0
    2
    Fatigue
         subjects affected / exposed
    4 / 63 (6.35%)
    1 / 61 (1.64%)
    2 / 61 (3.28%)
    1 / 57 (1.75%)
         occurrences all number
    4
    1
    2
    1
    Infusion site erythema
         subjects affected / exposed
    4 / 63 (6.35%)
    1 / 61 (1.64%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences all number
    4
    1
    0
    54
    Infusion site pain
         subjects affected / exposed
    1 / 63 (1.59%)
    4 / 61 (6.56%)
    0 / 61 (0.00%)
    2 / 57 (3.51%)
         occurrences all number
    1
    5
    0
    3
    Infusion site swelling
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 61 (1.64%)
    1 / 61 (1.64%)
    3 / 57 (5.26%)
         occurrences all number
    0
    2
    1
    3
    Injection site pain
         subjects affected / exposed
    2 / 63 (3.17%)
    5 / 61 (8.20%)
    0 / 61 (0.00%)
    0 / 57 (0.00%)
         occurrences all number
    2
    11
    0
    0
    Injection site swelling
         subjects affected / exposed
    2 / 63 (3.17%)
    7 / 61 (11.48%)
    1 / 61 (1.64%)
    4 / 57 (7.02%)
         occurrences all number
    33
    48
    44
    22
    Oedema
         subjects affected / exposed
    3 / 63 (4.76%)
    5 / 61 (8.20%)
    1 / 61 (1.64%)
    1 / 57 (1.75%)
         occurrences all number
    4
    6
    1
    1
    Pyrexia
         subjects affected / exposed
    12 / 63 (19.05%)
    7 / 61 (11.48%)
    5 / 61 (8.20%)
    4 / 57 (7.02%)
         occurrences all number
    14
    7
    7
    4
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 63 (6.35%)
    4 / 61 (6.56%)
    2 / 61 (3.28%)
    3 / 57 (5.26%)
         occurrences all number
    6
    5
    2
    3
    Diarrhoea
         subjects affected / exposed
    2 / 63 (3.17%)
    7 / 61 (11.48%)
    4 / 61 (6.56%)
    8 / 57 (14.04%)
         occurrences all number
    3
    8
    5
    9
    Nausea
         subjects affected / exposed
    6 / 63 (9.52%)
    4 / 61 (6.56%)
    6 / 61 (9.84%)
    2 / 57 (3.51%)
         occurrences all number
    8
    4
    10
    2
    Vomiting
         subjects affected / exposed
    5 / 63 (7.94%)
    9 / 61 (14.75%)
    7 / 61 (11.48%)
    2 / 57 (3.51%)
         occurrences all number
    7
    13
    10
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 63 (9.52%)
    1 / 61 (1.64%)
    4 / 61 (6.56%)
    1 / 57 (1.75%)
         occurrences all number
    7
    1
    5
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 63 (0.00%)
    4 / 61 (6.56%)
    0 / 61 (0.00%)
    1 / 57 (1.75%)
         occurrences all number
    0
    4
    0
    1
    Pruritus
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 61 (0.00%)
    4 / 61 (6.56%)
    3 / 57 (5.26%)
         occurrences all number
    2
    0
    4
    5
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    0 / 63 (0.00%)
    4 / 61 (6.56%)
    1 / 61 (1.64%)
    0 / 57 (0.00%)
         occurrences all number
    0
    4
    1
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    2 / 63 (3.17%)
    4 / 61 (6.56%)
    3 / 61 (4.92%)
    1 / 57 (1.75%)
         occurrences all number
    2
    4
    3
    1
    Influenza
         subjects affected / exposed
    6 / 63 (9.52%)
    3 / 61 (4.92%)
    4 / 61 (6.56%)
    1 / 57 (1.75%)
         occurrences all number
    6
    4
    4
    1
    Nasopharyngitis
         subjects affected / exposed
    11 / 63 (17.46%)
    7 / 61 (11.48%)
    7 / 61 (11.48%)
    3 / 57 (5.26%)
         occurrences all number
    15
    8
    9
    3
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 63 (6.35%)
    5 / 61 (8.20%)
    4 / 61 (6.56%)
    1 / 57 (1.75%)
         occurrences all number
    4
    5
    5
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Mar 2021
    Updated study design so that the RCP was double-blinded and added justification of study design section. Shortened the follow-up period for subjects who did not continued receiving pegcetacoplan from 24 to 8 weeks. Added an interim analysis of efficacy when all subjects had completed the 26-week RCP. Revised the endpoints. Amended inclusion and exclusion criteria. Revised dosing recommendations, added regimens for adolescent subjects >=50 kg, 35 to <50 kg, and 20 to <35 kg. Update wording describing monitoring and reporting of AEs and SAEs to align with current company practices. Added wording describing risks related coronavirus disease 2019 (COVID-19) and activities to mitigate these risks.
    14 Aug 2021
    Changed planned enrollment from 90 to 80-100 subjects. Clarified vaccination strategy and prophylactic antibiotic use in Risk/Benefit discussion. Changed primary and key secondary objectives to align with endpoint changes. Changed primary efficacy endpoint to remove eGFR component. Changed primary and key secondary efficacy endpoints from Week 52 to Week 26. Increased minimum body weight to 30 kg. Removed discussion of extrapolating placebo response rate from Week 26 to Week 52. Removed interim analyses (interim analysis 1 for sample size readjustment and interim analysis 2 for early efficacy assessment). Added COVID-19 vaccine to COVID-19 risk mitigation section and COVID-19 Appendix.
    03 Mar 2023
    Increased duration of screening period from 8 to 10 weeks with a corresponding increase of total duration of study participation to 70 weeks. Increased the minimum number of adolescent participants from 8 to 10. Revised endpoints. Updated discussion of the determination of sample size. Updated the discussion of the efficacy analyses. Updated discussion of assessment of severity of AEs.
    25 Apr 2024
    Order of key secondary endpoints revised. Removed exploratory endpoint evaluating normalization of hematuria. Removed exploratory endpoint of evaluation of changes in drusen at 26 weeks. Revised description of the data review for the analysis set. Added description of the activities at the closure of enrollment. Revised description of antidrug antibody assessments.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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