Clinical Trial Results:
An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Lanadelumab for Prevention Against Acute Attacks of Nonhistaminergic Angioedema with Normal C1-Inhibitor (C1-INH)
|
Summary
|
|
EudraCT number |
2019-004823-20 |
Trial protocol |
DE HU PL NL IT FR |
Global end of trial date |
05 May 2023
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
08 May 2024
|
First version publication date |
08 May 2024
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
TAK-743-3001
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04444895 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Takeda
|
||
Sponsor organisation address |
95 Hayden Avenue, Lexington, United States, MA 02421
|
||
Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
|
||
Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
05 May 2023
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
05 May 2023
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The purpose of this study was to check the safety and efficacy of lanadelumab for prevention of acute attacks of non-histaminergic angioedema with normal C1-inhibitor
|
||
Protection of trial subjects |
All study participants were required to read and sign an informed consent form.
|
||
Background therapy |
N/A | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
05 Feb 2021
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Canada: 5
|
||
Country: Number of subjects enrolled |
France: 1
|
||
Country: Number of subjects enrolled |
Germany: 3
|
||
Country: Number of subjects enrolled |
Hungary: 2
|
||
Country: Number of subjects enrolled |
Italy: 7
|
||
Country: Number of subjects enrolled |
Japan: 4
|
||
Country: Number of subjects enrolled |
Netherlands: 3
|
||
Country: Number of subjects enrolled |
Poland: 6
|
||
Country: Number of subjects enrolled |
Spain: 3
|
||
Country: Number of subjects enrolled |
United States: 39
|
||
Worldwide total number of subjects |
73
|
||
EEA total number of subjects |
25
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
70
|
||
From 65 to 84 years |
3
|
||
85 years and over |
0
|
||
|
|||||||||||||||||
|
Recruitment
|
|||||||||||||||||
Recruitment details |
A total of 73 participants took part in the study at 34 investigative sites in Canada, France, Germany, Hungary, Italy, Japan, Netherlands, Poland, Spain, and the United States from 05 February 2021 to 05 May 2023. | ||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||
Screening details |
Participants with a diagnosis of non-histaminergic angioedema rolled over from the study SHP643-303 (NCT04206605) to receive lanadelumab 300 mg every 2 weeks (Q2W) of whom 2 participants switched to lanadelumab 300 mg at a reduced frequency of every 4 weeks (Q4W) for some time during the study. | ||||||||||||||||
|
Period 1
|
|||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||
|
Arms
|
|||||||||||||||||
|
Arm title
|
Lanadelumab 300 mg Q2W | ||||||||||||||||
Arm description |
Participants received 300 milligrams (mg) lanadelumab subcutaneous (SC) injection, every 2 weeks (Q2W) for up to 26 weeks with an option to switch to lanadelumab 300 mg every 4 weeks (Q4W) if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Lanadelumab 300 mg
|
||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||
Other name |
DX-2930, SHP-643, TAK-743
|
||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled syringe
|
||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||
Dosage and administration details |
300 mg (300 mg/2 mL), Subcutaneous (SC) injection
|
||||||||||||||||
|
|||||||||||||||||
| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Reduced-dose Safety Analysis Set includes participants who switched to lanadelumab 300 mg at a reduced frequency of every 4 weeks (Q4W) for some time during the study. |
|||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lanadelumab 300 mg Q2W
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received 300 milligrams (mg) lanadelumab subcutaneous (SC) injection, every 2 weeks (Q2W) for up to 26 weeks with an option to switch to lanadelumab 300 mg every 4 weeks (Q4W) if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Lanadelumab 300 mg Q4W
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator’s discretion and consultation with the sponsor’s medical monitor at any point during the 26-week treatment period were included in this group.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Lanadelumab 300 mg Q2W
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants who received 300 mg lanadelumab SC injection, Q2W, and switched to the Q4W regimen as attacks were well-controlled based on the investigator’s discretion and consultation with the sponsor’s medical monitor at any point during the 26-week treatment period were included in this group.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Lanadelumab 300 mg Q2W
|
||
Reporting group description |
Participants received 300 milligrams (mg) lanadelumab subcutaneous (SC) injection, every 2 weeks (Q2W) for up to 26 weeks with an option to switch to lanadelumab 300 mg every 4 weeks (Q4W) if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor. | ||
Subject analysis set title |
Lanadelumab 300 mg Q4W
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator’s discretion and consultation with the sponsor’s medical monitor at any point during the 26-week treatment period were included in this group.
|
||
Subject analysis set title |
Lanadelumab 300 mg Q2W
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants who received 300 mg lanadelumab SC injection, Q2W, and switched to the Q4W regimen as attacks were well-controlled based on the investigator’s discretion and consultation with the sponsor’s medical monitor at any point during the 26-week treatment period were included in this group.
|
||
|
||||||||||||||||||||||||||||
End point title |
Number of Participants with Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Treatment Period [1] | |||||||||||||||||||||||||||
End point description |
TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.
|
|||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||
End point timeframe |
From Day 0 up to Day 182
|
|||||||||||||||||||||||||||
| 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 analyses were planned for this endpoint. |
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Number of Participants with Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Follow-up [2] | |||||||||||||||||||||||||||
End point description |
TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.
|
|||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||
End point timeframe |
From Day 183 up to Day 196
|
|||||||||||||||||||||||||||
| 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 analyses were planned for this endpoint. |
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 | ||||||||||||
End point description |
An angioedema attack was 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). Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 was assessed. The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Day 0 up to Day 182
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 | ||||||||||||
End point description |
The overall severity of angioedema attack was determined by the site using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Number of moderate or severe angioedema attacks during the treatment period of Day 0 through Day 182 was assessed. The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Day 0 up to Day 182
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 | ||||||||||||
End point description |
A high-morbidity angioedema attack was defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation <24 hours), hemodynamically significant (systolic blood pressure (BP) <90 millimetres of mercury (mmHg), requires intravenous hydration, or associated with syncope or near-syncope) or laryngeal. The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Day 0 up to Day 182
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||
End point title |
Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab | ||||||||||||||||||||||||
End point description |
The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen. The Pharmacokinetic (PK) Set included all participants in the SFAS who had at least 1 evaluable postdose PK concentration value. Subjects analysed is the number of participants with data available for analyses. ‘n’ signifies number of participants analysed at specific time point. 9999 indicates that the standard deviation was not estimable as the values were below the lower limit of quantification. 999 indicates that the standard deviation was not estimable for a single participant.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Predose on Days 0, 84, and 140 and postdose on Day 182
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Plasma Kallikrein (pKal) Activity | ||||||||||||||||||||||||
End point description |
Plasma kallikrein activity was measured by biomarker cleaved high molecular weight kininogen (cHMWK) with factor XIIa activation level to assess the pharmacodynamics of lanadelumab. The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen. The Pharmacodynamic (PD) Set included all participants in the SFAS who had at least 1 evaluable postdose PD concentration value. Subjects analysed is the number of participants with data available for analyses. ‘n’ signifies number of subjects analyzed at specific time point. 9999 indicates that the standard deviation was not estimable as the values were below the lower limit of quantification. 999 indicates that the standard deviation was not estimable for a single participant.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Predose on Days 0, 84, and 140 and postdose on Day 182
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||
End point title |
Number of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma | ||||||||||||||
End point description |
Number of participants with positive ADA including evaluation of neutralizing antibodies in plasma was assessed. As pre-specified in the statistical analysis plan (SAP), data for this outcome measure was collected and analyzed as a single group irrespective of dosing regimen. The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). Subjects analysed is the number of participants with data available for analyses. ‘n’ signifies number of subjects analyzed at specific time point.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Predose on Days 0, 84, and 140 and postdose on Day 182
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||
End point title |
Change From Baseline in Total Angioedema Quality of life (AE-QoL) Questionnaire Total Score at End of Treatment Period | ||||||||||
End point description |
The AE-QoL questionnaire is self-administered validated instrument to assess health related (HR)QoL among participants with recurrent angioedema(including hereditary angioedema[HAE]). It consists of 17 disease-specific QOL items, to produce total AE-QoL score & 4 domain scores(functioning,fatigue/mood,fear/shame,nutrition) each of 17 items had 5-point response scale ranging from 1(Never) to 5(Very Often). It was scored according to developers' guidelines to produce 4 domain scores yielding total score. The raw total score(mean of all item scores) was rescaled using linear transformations into final percentage scores ranging 0-100, based on maximum possible score, where higher score, greater QoL impairment. Negative change from Baseline indicates better QoL. Baseline: Last non-missing value prior to first exposure to study drug(based on date or date/time). As pre-specified in SAP, data for this outcome measure was collected and analyzed as single group irrespective of dosing regimen.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Baseline (Day 0) up to end of treatment period (Day 182)
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants with Any Pause During Injection | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
An injection report was completed by the participant (or parent/caregiver following each dose administration of lanadelumab injection used during the treatment period and any kind of pause during injection was captured. Categories with at least one participant with event are reported. The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). ‘n’ signifies number of participants analysed at specific time point. The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Days 0, 14, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, and 168
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Number of Participants with Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) in Participants who Switched Dosing Regimen | |||||||||||||||||||||||||||
End point description |
TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
From Day 0 up to Day 196
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants who Switched Dosing Regimen | ||||||||||||
End point description |
An angioedema attack was 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). Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 was assessed. The RD-SFAS Set was a subset of the SFAS Set and included participants who switched from lanadelumab 300 mg Q2W to a lanadelumab 300 mg Q4W dosing regimen as recorded on the Dose Frequency Modification electronic case report form. The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Day 0 up to Day 182
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants who Switched Dosing Regimen | ||||||||||||
End point description |
The overall severity of angioedema attack was determined by the site using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Number of moderate or severe angioedema attacks during the treatment period of Day 0 through Day 182 was assessed. The RD-SFAS Set was a subset of the SFAS Set and included participants who switched from lanadelumab 300 mg Q2W to a lanadelumab 300 mg Q4W dosing regimen as recorded on the Dose Frequency Modification electronic case report form. The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Day 0 up to Day 182
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 through Day 182 in Participants who Switched Dosing Regimen | ||||||||||||
End point description |
A high-morbidity angioedema attack was defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation <24 hours), hemodynamically significant (systolic BP <90 mmHg, requires intravenous hydration, or associated with syncope or near-syncope) or laryngeal. The RD-SFAS Set was a subset of the SFAS Set and included participants who switched from lanadelumab 300 mg Q2W to a lanadelumab 300 mg Q4W dosing regimen as recorded on the Dose Frequency Modification electronic case report form. The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Day 0 up to Day 182
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From the first study drug administration up to follow-up (Day 196)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The SFAS included all participants who received any study drug after entering this study (i.e., any exposure to open-label lanadelumab). The data was partitioned by dosing regimen and reported accordingly to appropriately attribute to each dosing regimen.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lanadelumab 300 mg Every 4 Weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants who received 300 mg lanadelumab, SC injection, Q4W as attacks were well-controlled based on the investigator’s discretion and consultation with the sponsor’s medical monitor at any point during the 26-week treatment period were included in this group. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lanadelumab 300 mg Every 2 Weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received 300 mg lanadelumab SC injection, Q2W for up to 26 weeks with an option to switch to lanadelumab 300 mg Q4W if attacks were well-controlled based on the investigator’s discretion and consultation with the sponsor’s medical monitor. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
14 Sep 2020 |
The following changes were made as per Amendment 1: 1. Included Takeda
appropriate forms for AEs and pregnancy. 2. Removed specificity to European
Union and Israel 3. Removed references to acquired angioedema due to C1-INH. 4.
Removed exclusion criteria 5. Corrected errors referring to treatment period. 6.
PK and PD analysis sets were added and "concentration" was removed in regard to
plasma cHMWK and pKal levels. 7. Revised exploratory biomarkers to state
“…angioedema-disease state bioactivity, including pKal activity.” 8. Visits 5
and 9 were revised to subject-elected off-site visits. 9. Timing of site
check-in calls was added. 10. Added study procedure modifications due to
coronavirus disease (COVID) pandemic. 11. Secondary objective with regard to
prefilled syringe was revised to state “to evaluate subject experience of
injection. 12. Added section on collection of angioedema attack data. 13.
Revised HAE attack to angioedema attack. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| N/A | |||
