Clinical Trial Results:
SPRING STUDY: An Open-Label, Multicenter, Phase 3 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab for Prevention Against Acute Attacks of Hereditary Angioedema (HAE) in Pediatric Subjects 2 to <12 Years of Age
Summary
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EudraCT number |
2018-002093-42 |
Trial protocol |
DE HU ES Outside EU/EEA |
Global end of trial date |
30 Oct 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
15 May 2022
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First version publication date |
15 May 2022
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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 |
SHP643-301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04070326 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND Number: 116647 | ||
Sponsors
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Sponsor organisation name |
Shire
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Sponsor organisation address |
300 Shire Way, Lexington, United States, MA 02421
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Public contact |
Study Director, Shire, ClinicalTransparenc@takeda.com
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Scientific contact |
Study Director, Shire, ClinicalTransparenc@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001864-PIP01-15 | ||
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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Oct 2021
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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 |
30 Oct 2021
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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 was to evaluate the safety and pharmacokinetics (PK) of lanadelumab in children (2 to <12 years of age) with HAE.
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Protection of trial subjects |
All study participants were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Aug 2019
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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 |
Spain: 1
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Country: Number of subjects enrolled |
Germany: 4
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
United States: 13
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Country: Number of subjects enrolled |
Canada: 2
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Worldwide total number of subjects |
21
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EEA total number of subjects |
6
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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) |
21
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Total 24 participants were screened and 21 participants were enrolled in the study at 15 investigative sites in the US, Canada, Spain, Hungary, and Germany from 19 August 2019 to 30 October 2021. | |||||||||||||||
Pre-assignment
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Screening details |
Participants were observed in 12-week Baseline Observation Period. Participants experiencing ≥1.0 angioedema attacks/3 months during 12-week Baseline Observation Period,who remained eligible per inclusion criteria entered treatment period(TP).Participants aged 2 to <12 years received lanadelumab SC Injection over 52-week Treatment Period. | |||||||||||||||
Period 1
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Period 1 title |
Baseline Observation-12 Weeks Before TP
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Non-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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Lanadelumab 150 mg: Age 2 to <6 Years | |||||||||||||||
Arm description |
Participants aged 2 to <6 years received lanadelumab subcutaneous (SC) injection at a dose of 150 milligrams (mg) for every 4 weeks (q4wks) over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Lanadelumab
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Investigational medicinal product code |
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Other name |
TAK-743, DX-2930, SHP643
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Pharmaceutical forms |
Intravesical solution/solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week Treatment Period.
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Arm title
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Lanadelumab 150 mg: Age 6 to <12 Years | |||||||||||||||
Arm description |
Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for every 2 weeks (q2wks) 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study.Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for every 2 weeks (q2wks) over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Lanadelumab
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Investigational medicinal product code |
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Other name |
TAK-743, DX-2930, SHP643
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Pharmaceutical forms |
Intravesical solution/solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week Treatment Period.
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Period 2
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Period 2 title |
Treatment Period A (Weeks 1 to 26)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Non-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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Lanadelumab 150 mg: Age 2 to <6 Years | |||||||||||||||
Arm description |
Participants aged 2 to <6 years received lanadelumab SC injection at a dose of 150 mg for q4wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Lanadelumab
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Investigational medicinal product code |
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Other name |
TAK-743, DX-2930, SHP643
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Pharmaceutical forms |
Intravesical solution/solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week Treatment Period.
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Arm title
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Lanadelumab 150 mg: Age 6 to <12 Years | |||||||||||||||
Arm description |
Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Lanadelumab
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Investigational medicinal product code |
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Other name |
TAK-743, DX-2930, SHP643
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Pharmaceutical forms |
Intravesical solution/solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week Treatment Period.
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Period 3
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Period 3 title |
Treatment Period B (Weeks 27 to 52)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Non-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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Lanadelumab 150 mg: Age 2 to <6 Years | |||||||||||||||
Arm description |
Participants aged 2 to <6 years received lanadelumab SC injection at a dose of 150 mg for q4wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Lanadelumab
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Investigational medicinal product code |
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Other name |
TAK-743, DX-2930, SHP643
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Pharmaceutical forms |
Intravesical solution/solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week Treatment Period.
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Arm title
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Lanadelumab 150 mg: Age 6 to <12 Years | |||||||||||||||
Arm description |
Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Lanadelumab
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Investigational medicinal product code |
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Other name |
TAK-743, DX-2930, SHP643
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Pharmaceutical forms |
Intravesical solution/solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received 150 mg dose of lanadelumab every 2 or 4 weeks, depending on the participants age, over the 52-week Treatment Period.
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Baseline characteristics reporting groups
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Reporting group title |
Lanadelumab 150 mg: Age 2 to <6 Years
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Reporting group description |
Participants aged 2 to <6 years received lanadelumab subcutaneous (SC) injection at a dose of 150 milligrams (mg) for every 4 weeks (q4wks) over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lanadelumab 150 mg: Age 6 to <12 Years
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Reporting group description |
Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for every 2 weeks (q2wks) 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study.Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for every 2 weeks (q2wks) over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lanadelumab 150 mg: Age 2 to <6 Years
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Reporting group description |
Participants aged 2 to <6 years received lanadelumab subcutaneous (SC) injection at a dose of 150 milligrams (mg) for every 4 weeks (q4wks) over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). | ||
Reporting group title |
Lanadelumab 150 mg: Age 6 to <12 Years
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Reporting group description |
Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for every 2 weeks (q2wks) 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study.Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for every 2 weeks (q2wks) over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study. | ||
Reporting group title |
Lanadelumab 150 mg: Age 2 to <6 Years
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Reporting group description |
Participants aged 2 to <6 years received lanadelumab SC injection at a dose of 150 mg for q4wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). | ||
Reporting group title |
Lanadelumab 150 mg: Age 6 to <12 Years
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Reporting group description |
Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study. | ||
Reporting group title |
Lanadelumab 150 mg: Age 2 to <6 Years
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Reporting group description |
Participants aged 2 to <6 years received lanadelumab SC injection at a dose of 150 mg for q4wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). | ||
Reporting group title |
Lanadelumab 150 mg: Age 6 to <12 Years
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Reporting group description |
Participants aged 6 to <12 years received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). Participants could switch to a dosing regimen of 150 mg q4wks in Treatment Period B at the investigator’s discretion and sponsor’s medical monitor approval, if they were well controlled (e.g., attack free) for 26 weeks with lanadelumab treatment in this study. | ||
Subject analysis set title |
Lanadelumab 150 mg, q4wks
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
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Subject analysis set title |
Lanadelumab 150 mg, q2wks
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B).
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End point title |
Number of Participants with Adverse Events Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) [1] | |||||||||||||||
End point description |
Adverse event(AE):any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with investigational product or medicinal product.SAE:any untoward clinical manifestation of signs,symptoms or outcomes(whether considered related to investigational product or not and at any dose which results in death,is life-threatening,requires inpatient hospitalization or prolongation of hospitalization,results in persistent or significant disability/incapacity,results in congenital abnormality/birth defect,is important medical event.AEs of special interest(AESIs):are hypersensitivity reactions and disordered coagulation(hypercoagulability events and bleeding events).Safety Analysis Set:all participants who received study drug.'n'=participants presented by actual treatment regimen.Due to dose modifications,some participants treated with both dosing regimens were counted in both treatment groups.
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End point type |
Primary
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End point timeframe |
Up to approximately 115 weeks
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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: Only descriptive summary statistics was planned for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Number of Participants With Clinically Significant Laboratory Assessment Abnormalities [2] | |||||||||
End point description |
Laboratory values (chemistry, hematology, and coagulation) were to be considered clinically significant based on investigator's discretion. The Safety Analysis Set consisted of all participants who received study drug.
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End point type |
Primary
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End point timeframe |
Up to approximately 115 weeks
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Notes [2] - 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: Only descriptive summary statistics was planned for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Number of Participants With Clinically Significant Vital Signs Measurements [3] | |||||||||
End point description |
Vital signs included blood pressure, heart rate, body temperature, and respiratory rate. The Safety Analysis Set consisted of all participants who received study drug.
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End point type |
Primary
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End point timeframe |
Up to approximately 115 weeks
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Notes [3] - 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: Only descriptive summary statistics was planned for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Plasma Concentrations of Lanadelumab Over The Treatment Period [4] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The plasma concentration of lanadelumab over treatment period was assessed. The Pharmacokinetic (PK) Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-dose), Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
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Notes [4] - 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: Only descriptive summary statistics was planned for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Maximum Observed Concentration at Steady State (Cmax,ss) of Lanadelumab in Plasma [5] | ||||||||||||
End point description |
The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
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Notes [5] - 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: Only descriptive summary statistics was planned for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Average Concentration Over Dosing Interval at Steady State (Cavg,ss) of Lanadelumab in Plasma [6] | ||||||||||||
End point description |
The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
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Notes [6] - 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: Only descriptive summary statistics was planned for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Minimum Concentration at Steady State (Cmin,ss) of Lanadelumab in Plasma [7] | ||||||||||||
End point description |
The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
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Notes [7] - 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: Only descriptive summary statistics was planned for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Time to Reach Maximum Observed Concentration (Cmax) [tmax] of Lanadelumab in Plasma [8] | ||||||||||||
End point description |
The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
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Notes [8] - 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: Only descriptive summary statistics was planned for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Lanadelumab in Plasma [9] | ||||||||||||
End point description |
The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
|
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Notes [9] - 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: Only descriptive summary statistics was planned for this outcome measure. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Terminal half-life (t1/2) of Lanadelumab in Plasma [10] | ||||||||||||
End point description |
The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
|
||||||||||||
Notes [10] - 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: Only descriptive summary statistics was planned for this outcome measure. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Apparent clearance (CL/F) of Lanadelumab [11] | ||||||||||||
End point description |
The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
|
||||||||||||
Notes [11] - 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: Only descriptive summary statistics was planned for this outcome measure. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Apparent Volume of Distribution (V/F) of Lanadelumab [12] | ||||||||||||
End point description |
The PK Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PK concentration value.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 0 (Pre-dose), at any time pre-dose on Day 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
|
||||||||||||
Notes [12] - 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: Only descriptive summary statistics was planned for this outcome measure. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Normalized Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Overall Treatment Period | ||||||||||||
End point description |
Normalized number of investigator-confirmed HAE attacks during overall period are expressed as monthly HAE attack rate.Investigator-confirmed HAE attack rate calculated for each participant as number of investigator-confirmed HAE attacks occurring during given study period divided by number of days participant contributed to period multiplied by 28days.HAE attack:symptoms/signs consistent with attack in>=1of following locations:peripheral angioedema(cutaneous swelling involving extremity,face,neck,torso,and/or genitourinary region),abdominal angioedema(abdominal pain,with/without abdominal distention,nausea,vomiting,/diarrhea),laryngeal angioedema(stridor,dyspnea,difficulty speaking,difficulty swallowing,throat tightening,/swelling of tongue,palate,uvula,/larynx).Safety Analysis Set: participants who received study drug.n=participants presented by actual treatment regimen;due to dose modifications,some them were treated with both dosing regimens,counted in both treatment groups.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 (after start of study drug administration) through Day 364 (Week 52)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Normalized Number of Investigator-Confirmed HAE Attacks For Each Efficacy Evaluation Period Other Than the Overall Treatment Period | ||||||||||||||||||||||||
End point description |
Normalized number of investigator-confirmed HAE attacks in each efficacy evaluation period except overall treatment period are expressed as monthly HAE attack rate and is calculated for each participant as number of investigator-confirmed HAE attacks occurring during given study period divided by number of days participant contributed to period multiplied by 28days.HAE attack:symptoms/signs consistent with attack in>=1of following locations:peripheral angioedema(cutaneous swelling involving extremity,face,neck,torso,and/or genitourinary region),abdominal angioedema(abdominal pain,with/without abdominal distention,nausea,vomiting,/diarrhea),laryngeal angioedema(stridor,dyspnea,difficulty speaking,difficulty swallowing,throat tightening,/swelling of tongue,palate,uvula,/larynx).Safety Analysis Set:participants who received study drug.n=participants presented by actual treatment;due to dose modifications,some of them were treated with both doses and counted in both treatment groups.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Time to the First Investigator-Confirmed HAE Attack for Each Evaluation Period | |||||||||||||||||||||||||||
End point description |
Time to first investigator-confirmed HAE attack for each efficacy evaluation period,was calculated from date and time of first dose to date and time of first investigator-confirmed HAE attack after first open-label dose for that efficacy evaluation period.HAE attack:symptoms/signs consistent with an attack in>=1of following locations:peripheral angioedema(cutaneous swelling involving extremity,face,neck,torso,and/or genitourinary region),abdominal angioedema(abdominal pain,with/without abdominal distention,nausea,vomiting,/diarrhea),laryngeal angioedema(stridor,dyspnea,difficulty speaking,difficulty swallowing,throat tightening,/swelling of tongue,palate,uvula,/larynx).Kaplan-Meier Method used for analysis.Safety Analysis Set:participants who received study drug.n=participants presented by actual treatment;due to dose modifications,some of them treated with both doses,counted in both treatment groups.99999:Median,95%CI not evaluable due to low number of events.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Normalized Number of HAE Attacks Requiring Acute Treatment for Each Efficacy Evaluation Period | |||||||||||||||||||||||||||
End point description |
Normalized number of investigator-confirmed HAE attacks requiring acute treatment during each efficacy evaluation period are expressed as monthly HAE attack rate and is calculated for each participant as number of investigator-confirmed HAE attacks occurring during given study period divided by number of days participant contributed to period multiplied by 28days.HAE attack:symptoms/signs consistent with attack in>=1of following locations:peripheral angioedema(cutaneous swelling involving extremity,face,neck,torso,and/or genitourinary region),abdominal angioedema(abdominal pain,with/without abdominal distention,nausea,vomiting,/diarrhea),laryngeal angioedema(stridor,dyspnea,difficulty speaking,difficulty swallowing,throat tightening,/swelling of tongue,palate,uvula,/larynx).Safety Analysis Set:participants who received study drug.n=participants presented by actual treatment;due to dose modifications,some of them were treated with both doses and counted in both treatment groups.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | |||||||||||||||||||||||||||
End point description |
Normalized number of moderate/severe investigator-confirmed HAE attacks requiring acute treatment during each efficacy evaluation period are expressed as monthly HAE attack rate,is calculated for each participant as number of investigator-confirmed HAE attacks occurring during given study period divided by number of days participant contributed to period multiplied by 28days.HAE attack:symptoms/signs consistent with attack in>=1of following locations:peripheral angioedema(cutaneous swelling involving extremity,face,neck,torso,and/or genitourinary region),abdominal angioedema(abdominal pain,with/without abdominal distention,nausea,vomiting,/diarrhea),laryngeal angioedema(stridor,dyspnea,difficulty speaking,difficulty swallowing,throat tightening,/swelling of tongue,palate,uvula,/larynx).Safety Analysis Set:participants received study drug.n=participants presented by actual treatment;due to dose modifications,some of them treated with both doses are counted in both treatment groups.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Normalized Number of High Morbidity Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | |||||||||||||||||||||||||||
End point description |
Normalized number of high morbidity investigator-confirmed HAE attacks requiring acute treatment during each efficacy evaluation period are expressed as monthly HAE attack rate,is calculated for each participant as number of investigator-confirmed HAE attacks occurring during given study period divided by number of days participant contributed to period multiplied by 28days.HAE attack:symptoms/signs consistent with attack in>=1of following locations:peripheral angioedema(cutaneous swelling involving extremity,face,neck,torso,and/or genitourinary region),abdominal angioedema(abdominal pain,with/without abdominal distention,nausea,vomiting,/diarrhea),laryngeal angioedema(stridor,dyspnea,difficulty speaking,difficulty swallowing,throat tightening,/swelling of tongue,palate,uvula,/larynx).Safety Analysis Set:participants received study drug.n=participants presented by actual treatment;due to dose modifications,some of them treated with both doses are counted in both treatment groups.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants with Characteristics of Investigator-Confirmed HAE Attacks for Each Efficacy Evaluation Period | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Characteristics of investigator-confirmed HAE attacks for each efficacy evaluation period included duration,severity,attack location,and rescue medication use.HAE attack:symptoms or signs consistent with an attack in >=1 of following locations:peripheral angioedema(cutaneous swelling involving an extremity,face,neck,torso,and/or genitourinary region),abdominal angioedema(abdominal pain,with or without abdominal distention,nausea,vomiting,or diarrhea),laryngeal angioedema(stridor,dyspnea,difficulty speaking,difficulty swallowing,throat tightening,or swelling of tongue,palate,uvula,or larynx).Safety Analysis Set:all participants who received study drug.Overall number analyzed:participants presented by actual treatment regimen. Because of dose modifications,some participants were treated with both dosing regimens and were counted in both treatment groups.Only categories with data are reported.TP:Treatment Period;PSSP:presumed steady state period.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of Participants with HAE Attack-Free Status for Each Evaluation Period | ||||||||||||||||||||||||
End point description |
A HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). The Safety Analysis Set consists of all participants who received study drug. Overall number analyzed are participants presented by the actual treatment regimen. Because of dose modifications, some participants were treated with both dosing regimens and were counted in both treatment groups.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Day 0 through Day 364, Day 0 through Day 182, Day 70 through Day 182, Day 183 through Day 364, Day 70 through Day 364
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Plasma Kallikrein (pKal) Activity | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
pKal activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) level to assess pharmacodynamics of lanadelumab. The Pharmacodynamic (PD) Set included all participants in the Safety Analysis Set who have at least 1 evaluable post dose PD value. Number analyzed is the number of participants with data available for analysis at the given timepoint.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 (Pre-dose), at any time on Days 4, 14, 28, 56, 84, 112, 140, 168, 182 196, 252, 308, 364 and 392
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants with Immunogenicity Status as Positive or Negative | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Immunogenicity was measured based on the presence or absence of neutralizing or non-neutralizing Anti-drug Antibody (ADA) in plasma. The Safety Analysis Set consisted of all participants who received study drug. Number analyzed are the number of participants with data available for given category.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 (Pre-dose), Days 28, 84, 140, 182, 196, 252, 308, 364 and 392
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to approximately 115 weeks
|
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Adverse event reporting additional description |
The Safety Analysis Set consists of all participants who received study drug. Due to dose modification, some participants were counted in both arms, and thus the overall number of participants analyzed in arms Lanadelumab 150 mg, q4wks and Lanadelumab 150 mg, q2wks were 11 and 18, respectively.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
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Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lanadelumab 150 mg, q4wks
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Reporting group description |
Participants received lanadelumab SC injection at a dose of 150 mg for q4wks with over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lanadelumab 150 mg, q2wks
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Reporting group description |
Participants received lanadelumab SC injection at a dose of 150 mg for q2wks over 52-week Treatment Period (26-week Treatment Period A and 26-week Treatment Period B). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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12 Aug 2019 |
The primary purpose of this amendment was to make following changes: The protocol requirements for reporting Serious Adverse Events (SAEs) have been updated. Revised self-administration instructions to allow participants aged 6 years or older to self-administer lanadelumab only after they have received appropriate training and assessed by the investigator as being capable of self-treatment. Participants less than 6 years of age must have a parent/caregiver self-administer lanadelumab. Removed the requirement for eligibility to include “a family history consistent with HAE I or II, or C1q within the normal range” since these elements are not necessary. Added the requirement to exclude participants with a known hypersensitivity to the investigational product or its components as a new exclusion criterion. The assay used for HIV testing at screening has been revised to a more robust testing procedure. The volume of blood to be collected from each participant has been decreased in consideration of the pediatric population. Removed non-applicable Adverse Event (AE) guidance on “Symptoms of the Disease under Study”, as all angioedema attacks are reported as AEs in this study. |
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22 Jun 2021 |
The primary purpose of this amendment was to make following changes: Sponsor approval and emergency contact information has been updated to reflect the current medical monitor. Individual participant participation duration was revised to clarify that maximum duration for study participation is 72 weeks. Participants receiving treatment q2wks may complete the study in 70 weeks. Revised follow-up period to 2-4 weeks as follow-up period depends on the treatment schedule. Participants receiving treatment q2wks will have a 2-week follow-up period (EOS Visit at Day 378); participants receiving treatment q4wks will have a 4-week follow-up period (EOS Visit at Day 392). The interim analysis summarizing data up to Treatment Period A has been removed as it is no longer planned. EOS/ET visit in footnote “a” was incorrectly written as Day 292. This has been corrected to Day 392. Text regarding Study DX-2930-04 as “ongoing” has been removed as this study has been completed. Severity categorization for AEs was revised to clarify a portion of the protocol template language that is incongruous with program data collection and analysis procedures in the previous HAE clinical 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 |