Clinical Trial Results:
A Randomized, Open-Label, Two-Arm Study to Evaluate the Safety, Efficacy, and Pharmacodynamic Effects of Pozelimab and Cemdisiran Combination Treatment in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy
Summary
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EudraCT number |
2020-005005-17 |
Trial protocol |
HU |
Global end of trial date |
18 Oct 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Nov 2024
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First version publication date |
02 Nov 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
R3918-PNH-2092
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04811716 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Regeneron Pharmaceuticals, Inc.
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Sponsor organisation address |
777 Old Saw Mill River Road, Tarrytown, NY, United States, 10591
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Public contact |
Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
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Scientific contact |
Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Oct 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Oct 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study is to evaluate the safety and tolerability of 2 dosing regimens
of pozelimab and cemdisiran combination therapy during the open-label treatment period (OLTP)
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Protection of trial subjects |
It is the responsibility of both the sponsor and the investigator(s) to ensure that this clinical study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the ICH guidelines for GCP and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Jul 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Hong Kong: 1
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
Korea, Republic of: 12
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Country: Number of subjects enrolled |
Malaysia: 4
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Country: Number of subjects enrolled |
Taiwan: 4
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Country: Number of subjects enrolled |
United Kingdom: 2
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Worldwide total number of subjects |
24
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EEA total number of subjects |
1
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
19
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||
Pre-assignment
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Screening details |
Twenty-four participants were screened and randomized. | |||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Pozelimab Q2W + Cemdisiran | |||||||||||||||
Arm description |
Pozelimab administered by subcutaneous (SC) injection every 2 weeks (Q2W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment (pozelimab Q2W + cemdisiran) was administered on day 1 of the open-label treatment period (OLTP). In the open¬ label extension period (OLEP), participants received a regimen of pozelimab + cemdisiran, regardless of their treatment assignment in the OLTP. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Pozelimab
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Investigational medicinal product code |
REGN3918
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Administered by subcutaneous (SC) injection
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Arm title
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Pozelimab Q4W + Cemdisiran | |||||||||||||||
Arm description |
Pozelimab administered by subcutaneous (SC) injection every 4 weeks (Q4W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment was administered on day 1 of the OLTP. In the OLEP, participants received a regimen of pozelimab Q4W + cemdisiran, regardless of their treatment assignment in the OLTP. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Cemdisiran
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Investigational medicinal product code |
ALN-CC5
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Administered by subcutaneous (SC) injection
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Baseline characteristics reporting groups
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Reporting group title |
Pozelimab Q2W + Cemdisiran
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Reporting group description |
Pozelimab administered by subcutaneous (SC) injection every 2 weeks (Q2W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment (pozelimab Q2W + cemdisiran) was administered on day 1 of the open-label treatment period (OLTP). In the open¬ label extension period (OLEP), participants received a regimen of pozelimab + cemdisiran, regardless of their treatment assignment in the OLTP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pozelimab Q4W + Cemdisiran
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Reporting group description |
Pozelimab administered by subcutaneous (SC) injection every 4 weeks (Q4W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment was administered on day 1 of the OLTP. In the OLEP, participants received a regimen of pozelimab Q4W + cemdisiran, regardless of their treatment assignment in the OLTP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pozelimab Q2W + Cemdisiran
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Reporting group description |
Pozelimab administered by subcutaneous (SC) injection every 2 weeks (Q2W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment (pozelimab Q2W + cemdisiran) was administered on day 1 of the open-label treatment period (OLTP). In the open¬ label extension period (OLEP), participants received a regimen of pozelimab + cemdisiran, regardless of their treatment assignment in the OLTP. | ||
Reporting group title |
Pozelimab Q4W + Cemdisiran
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Reporting group description |
Pozelimab administered by subcutaneous (SC) injection every 4 weeks (Q4W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment was administered on day 1 of the OLTP. In the OLEP, participants received a regimen of pozelimab Q4W + cemdisiran, regardless of their treatment assignment in the OLTP. | ||
Subject analysis set title |
Pozelimab Q4W + Cemdisiran
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Pozelimab administered by subcutaneous (SC) injection every 4 weeks (Q4W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment was administered on day 1 of the OLTP. In the OLEP, participants received a regimen of pozelimab Q4W + cemdisiran, regardless of their treatment assignment in the OLTP.
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Subject analysis set title |
Pozelimab Q4W + Cemdisiran
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Pozelimab administered by subcutaneous (SC) injection every 4 weeks (Q4W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment was administered on day 1 of the OLTP. In the OLEP, participants received a regimen of pozelimab Q4W + cemdisiran, regardless of their treatment assignment in the OLTP.
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End point title |
Percentage of participants with treatment emergent adverse events (TEAEs) [1] | |||||||||||||||||||||
End point description |
Safety analysis set (SAS) included all randomized participants who received any amount of study drug and was based on the treatment received (as treated); Here 'number analyzed' = the number of evaluable participants at a specified timepoint
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End point type |
Primary
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End point timeframe |
Through Week 28
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
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No statistical analyses for this end point |
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End point title |
Percent change of Lactate dehydrogenase (LDH) from pre-treatment to end-of-treatment period | ||||||||||||
End point description |
OLTP
Pre-treatment (mean of LDH values prior to combination dosing); End-of-treatment (mean of LDH value at week 24- through week 28); Full analysis set (FAS) = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); percentage of change in Upper Limit of Normal (xULN); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
End of treatment period, approximately 28 Weeks
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Maintaining Adequate Control of Hemolysis from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP
Adequate control of hemolysis is defined as LDH values ≤1.5 x Upper limit of normal (ULN) from baseline (day 1) to week 28; Full analysis set (FAS) = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) through Week 28
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Maintaining Adequate Control of Hemolysis from Week 4 through Week 28 | ||||||||||||
End point description |
OLTP
Full analysis set (FAS) = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Week 4 through Week 28
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Adequate Control of Hemolysis at Each Visit from Baseline (Day 1) through Week 28 | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
OLTP; Adequate control at a visit is defined as having LDH <=1.5 x ULN at that visit; FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) through Week 28
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Normalization of LDH at Each Visit from Baseline (Day 1) through Week 28 | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
OLTP; Normalization of LDH was defined as LDH ≤1.0 × ULN at each visit; FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) through Week 28
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No statistical analyses for this end point |
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End point title |
Area under the curve (AUC) of LDH over time from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP; FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) through Week 28
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No statistical analyses for this end point |
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End point title |
AUC of LDH over time from Week 4 through Week 28 | ||||||||||||
End point description |
OLTP; FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Week 4 through Week 28
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Breakthrough hemolysis from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP; Breakthrough hemolysis = increase in LDH with concomitant signs or symptoms associated with hemolysis:
• Increase in LDH occurs when:
− LDH ≥2 × ULN if pre-treatment LDH is ≤1.5 × ULN or
− LDH ≥2 × ULN after initial achievement of LDH ≤1.5 × ULN if pre-treatment LDH is >1.5 × ULN
Signs/symptoms should correspond to those known to be associated with intravascular hemolysis due to Paroxysmal nocturnal hemoglobinuria (PNH) limited to the following: new onset or worsening fatigue, headache, dyspnea, hemoglobinuria, abdominal pain, scleral icterus, erectile dysfunction, chest pain, confusion, dysphagia, anemia including hemoglobin value significantly lower (ie, ≥2g/dL decrease) compared to participant’s baseline hemoglobin value, & thrombotic event. FAS = all randomized participants who received any study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) through Week 28
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Hemoglobin Stabilization from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP
Hemoglobin stabilization was defined as participants who did not receive an RBC transfusion and had no decrease in hemoglobin level of ≥2 grams per deciLiter (g/dL). FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) through Week 28
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No statistical analyses for this end point |
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End point title |
Change in Hemoglobin Levels from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP; FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 28
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Transfusion Avoidance from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP
Not requiring a red blood cell (RBC) transfusion as per protocol algorithm; FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 28
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No statistical analyses for this end point |
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End point title |
Rate of Red Blood Cells (RBCs) transfused from Baseline (Day 1) to Week 28 | ||||||||||||
End point description |
OLTP
Rate of RBCs transfused is defined as number of events per patient-years. For each participant, the participant-years are the time from first dose date to week 28 (or early terminations visit if subject discontinued the study early) in the OLTP. FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 28
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No statistical analyses for this end point |
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End point title |
Number of Per-Protocol RBC Units Transfused from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP; FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 28
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No statistical analyses for this end point |
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End point title |
Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP
FACIT fatigue is a 13-item scale and for each item 4 is not at all fatigued to 0 very much fatigued. Higher FACIT-Fatigue scores indicate less fatigue (scores range from 0-52). A 5-point change is considered clinically meaningful; FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 28
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No statistical analyses for this end point |
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End point title |
Change in Total complement hemolysis activity assay (CH50) from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP; FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 28
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No statistical analyses for this end point |
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End point title |
Change in global health status/quality of life scale (GHS/QoL) on the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire core 30 items (EORTC QLQ-C30) from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP; EORTC QLQ-C30 has 30 items (i.e. single questions), 24 of which are aggregated into 9 multi-item scales: 5 functioning scales (physical, role, cognitive, emotional & social), 3 symptom scales (fatigue, pain & nausea/vomiting) & 1 global health status scale. The remaining 6 single-item (dyspnoea, appetite loss, sleep disturbance, constipation, diarrhoea & the financial impact) scales assess symptoms. All of the scales & single-item measures range in score from 0-100. Higher score for functioning scales & global health status equal a better level of functioning (i.e. a better state of participant), while higher scores on the symptom & single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant); FAS = included all randomized participants who received any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 28
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No statistical analyses for this end point |
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End point title |
Change in physical function (PF) scores on the EORTC QLQ-C30 from Baseline (Day 1) through Week 28 | ||||||||||||
End point description |
OLTP; The EORTC QLQ-C30 is a 30-item, self-administered, generic questionnaire that assesses health-related QoL across multiple domains, including GHS, global QoL, functioning (physical, role, emotional, cognitive, and social functioning), symptom scales (fatigue, nausea and vomiting, pain, appetite loss), and single items (dyspnea, insomnia, constipation, diarrhea, sleep, financial impact). EORTC QLQ-C30 domain scales range from 0 to 100, with lower scores indicating worse QoL and higher scores for symptom scales indicating worse symptoms. A 10-point change is considered meaningful; Full analysis set (FAS) = included all randomized participants who eceived any amount of study drug & had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Week 28
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No statistical analyses for this end point |
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End point title |
Concentrations of Total Pozelimab in Serum on Week 28 | ||||||||||||
End point description |
OLTP; The PK analysis set includes all treated participants who received any amount of study drug (SAF) and who had at least 1 non-missing analyte measurement following the first dose of combination treatment. The PK analysis set is based on the actual treatment received.
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End point type |
Secondary
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End point timeframe |
On Week 28
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|
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No statistical analyses for this end point |
|
|||||||||||||
End point title |
Concentrations of Cemdisiran in Plasma on Week 28 | ||||||||||||
End point description |
OLTP; The PK analysis set includes all treated participants who received any amount of study drug (SAF) and who had at least 1 non-missing analyte measurement following the first dose of combination treatment. The PK analysis set is based on the actual treatment received.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
On Week 28
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Concentrations of Total C5 on Week 28 | ||||||||||||
End point description |
OLTP; The PK analysis set includes all treated participants who received any amount of study drug (SAF) and who had at least 1 non-missing analyte measurement following the first dose of combination treatment. The PK analysis set is based on the actual treatment received.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
On Week 28
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of Participants with Pozelimab Anti-Drug Antibody (ADA) Responses Over Time | ||||||||||||||||||
End point description |
OLTP and OLEP; Anti-Drug Antibodies (ADA) Analysis Set; Here 'n' = the number of evaluable participants at a certain timepoint
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to Week 52
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Percentage of participants with TEAEs for participants who received treatment intensification | |||||||||||||||||||||
End point description |
OLTP
No participants received dose intensification during the study; Therefore, assessment of the safety of pozelimab + cemdisiran combination therapy in participants requiring dose intensification was not conducted; Safety analysis set (SAS) included all randomized participants who received any amount of study drug and was based on the treatment received (as treated); Here 'n' = the number of evaluable participants at a specified timepoint
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Through Week 28
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [2] - No participants received dose intensification; assessment was not conducted [3] - No participants received dose intensification; assessment was not conducted |
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of Participants with Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time | ||||||||||||||||||
End point description |
OLTP and OLEP; Anti-Drug Antibodies (ADA) Analysis Set; Here 'n' = the number of evaluable participants at a certain timepoint
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to Week 52
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change of LDH from Baseline (Day 1e) to Week 24e | ||||||||
End point description |
Optional Open-Label Extension Period (OLEP); OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 24e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percent Change of LDH from OLEP Baseline (Day 1e) to Week 24e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 24e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change of LDH from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percent change of LDH from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Percentage of change for units per liter (U/L); Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Participants Maintaining Adequate Control of Hemolysis from Baseline (Day 1e) through Week 24e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) through Week 24e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||
End point title |
Percentage of Participants with Adequate Control of Hemolysis at Each Visit from Baseline (Day 1e) through Week 52e | ||||||||||||||||||||||
End point description |
OLEP; Adequate control at a visit is defined as having LDH <=1.5 x ULN at that visit; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||
End point timeframe |
Baseline (Day 1e) through Week 52e
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Participants Maintaining Adequate Control of Hemolysis from Baseline (Day 1e) through Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) through Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||
End point title |
Percentage of Participants with Normalization of LDH at Each Visit from Baseline (Day 1e) through Week 52e | ||||||||||||||||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||
End point timeframe |
Baseline (Day 1e) through week 52e
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
AUC of LDH over time from Baseline (Day 1e) through Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) through Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Participants with Breakthrough hemolysis from Baseline (Day 1e) through Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) through Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Participants with Breakthrough hemolysis from Baseline (Day 1e) through Week 24e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) through Week 24e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Participants with Hemoglobin Stabilization from Baseline (Day 1e) through Week 24e | ||||||||
End point description |
OLEP
Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) through Week 24e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Participants with Hemoglobin Stabilization from Baseline (Day 1e) through Week 52e | ||||||||
End point description |
OLEP
Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) through Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change in hemoglobin levels from Baseline (Day 1e) to Week 24e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 24e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change in hemoglobin levels from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Participants with Per-Protocol Transfusion Avoidance from Baseline (Day 1e) through Week 24e | ||||||||
End point description |
OLEP
Not requiring a RBC transfusion as per protocol algorithm; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) through Week 24e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Participants with Per-Protocol Transfusion Avoidance from Baseline (Day 1e) through Week 52e | ||||||||
End point description |
OLEP
Not requiring a RBC transfusion as per protocol algorithm; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Number of units of RBCs transfused from Baseline (Day 1e) to Week 24e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 24e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Rate of RBCs transfused from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Rate of RBCs transfused from Baseline (Day 1e) to Week 24e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 24e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Number of units of RBCs transfused from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change in CH50 from Baseline (Day 1e) to Week 24e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint; Since all participants have 0 values at baseline for CH50, the percentage change is not appropriate and undefined. Therefore, this endpoint is not able to be calculated.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 24e
|
||||||||
|
|||||||||
Notes [4] - All participants have 0 values at baseline, percentage change is undefined and cannot be calculated. |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change in CH50 from Baseline (Day 1e) to Week 16e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 16e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change in CH50 from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percent change in CH50 from Baseline (Day 1e) to Week 16e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint; Since all participants have 0 values at baseline for CH50, the percentage change is not appropriate and undefined. Therefore, this endpoint is not able to be calculated.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 16e
|
||||||||
|
|||||||||
Notes [5] - All participants have 0 values at baseline, percentage change is undefined and cannot be calculated. |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percent change in CH50 from Baseline (Day 1e) to Week 24e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint; Since all participants have 0 values at baseline for CH50, the percentage change is not appropriate and undefined. Therefore, this endpoint is not able to be calculated.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 24e
|
||||||||
|
|||||||||
Notes [6] - All participants have 0 values at baseline, percentage change is undefined and cannot be calculated. |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percent change in CH50 from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint; Since all participants have 0 values at baseline for CH50, the percentage change is not appropriate and undefined. Therefore, this endpoint is not able to be calculated.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
Notes [7] - All participants have 0 values at baseline, percentage change is undefined and cannot be calculated. |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; The FACIT-Fatigue is a 13-item, self-administered assessment of an individual’s level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in participants with cancer and other chronic illnesses. The FACIT-Fatigue items are measured with a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating less fatigue. A 5-point change is considered clinically meaningful. OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change in GHS/QoL on the EORTC QLQ-C30 from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; The EORTC QLQ-C30 is a 30-item, self-administered, generic questionnaire that assesses health-related QoL across multiple domains, including GHS, global QoL, functioning (physical, role, emotional, cognitive, and social functioning), symptom scales (fatigue, nausea and vomiting, pain, appetite loss), and single items (dyspnea, insomnia, constipation, diarrhea, sleep, financial impact). EORTC QLQ-C30 domain scales range from 0 to 100, with lower scores indicating worse QoL and higher scores for symptom scales indicating worse symptoms. A 10-point change is considered meaningful. OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change in PF scores on the EORTC QLQ-C30 from Baseline (Day 1e) to Week 52e | ||||||||
End point description |
OLEP; The EORTC QLQ-C30 is a 30-item, self-administered, generic questionnaire that assesses health-related QoL across multiple domains, including GHS, global QoL, functioning (physical, role, emotional, cognitive, and social functioning), symptom scales (fatigue, nausea and vomiting, pain, appetite loss), and single items (dyspnea, insomnia, constipation, diarrhea, sleep, financial impact). EORTC QLQ-C30 domain scales range from 0 to 100, with lower scores indicating worse QoL and higher scores for symptom scales indicating worse symptoms. A 10-point change is considered meaningful.; OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Day 1e) to Week 52e
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Percentage of Participants with TEAEs Up to Week 52 | ||||||||||||||
End point description |
OLEP; SAS; Here 'n' = number of evaluable participants at a specified timepoint
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Up to Week 52
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Concentrations of Total Pozelimab in Serum on Week 52 | ||||||||||||
End point description |
OLEP; The OLEP PK analysis set includes all participants who participated in the OLEP who received any amount of study drug in the OLEP and who had at least 1 non-missing analyte measurement following the first dose of study drug in the OLEP.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
On Week 52
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Concentrations of Total C5 on Week 52 | ||||||||||||
End point description |
OLEP; The OLEP PK analysis set includes all participants who participated in the OLEP who received any amount of study drug in the OLEP and who had at least 1 non-missing analyte measurement following the first dose of study drug in the OLEP.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
On Week 52
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Concentrations of Cemdisiran in Plasma on Week 52 | ||||||||||||
End point description |
OLEP; The OLEP PK analysis set includes all participants who participated in the OLEP who received any amount of study drug in the OLEP and who had at least 1 non-missing analyte measurement following the first dose of study drug in the OLEP.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
On Week 52
|
||||||||||||
|
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
1. OLTP (from first dose up to Week 28 + follow-up of participant without OLE, total 24 participants)
2. OLEP (from Week 28 EOT up to Week 52 OLEP and up to Week 52 follow-up EOS, total 23 participants)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
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Reporting groups
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Reporting group title |
OLTP_Pozelimab Q2W + Cemdisiran
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Reporting group description |
Pozelimab administered by subcutaneous (SC) injection every 2 weeks (Q2W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment (pozelimab Q2W + cemdisiran) was administered on day 1 of the open-label treatment period (OLTP). In the open¬ label extension period (OLEP), participants received a regimen of pozelimab + cemdisiran, regardless of their treatment assignment in the OLTP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
OLEP_Pozelimab Q4W + Cemdisiran
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Reporting group description |
In the open-label extension period (OLEP), participants received a regimen of pozelimab SC Q4W + cemdisiran SC, regardless of their treatment assignment in the OLTP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
OLTP_Pozelimab Q4W + Cemdisiran
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Reporting group description |
Pozelimab administered by subcutaneous (SC) injection every 4 weeks (Q4W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment was administered on day 1 of the OLTP. In the OLEP, participants received a regimen of pozelimab Q4W + cemdisiran, regardless of their treatment assignment in the OLTP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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22 Dec 2021 |
The main purpose of this amendment was to modify the timing of the interim analysis and to align endpoints with other studies. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |