A Study of Lanadelumab in Teenagers and Adults With Hereditary Angioedema (HAE)

Demographic and Clinical Characteristics, Treatment Patterns, and Real-world Effectiveness of Lanadelumab in Patients With Hereditary Angioedema Type I or II in the United Kingdom: an Ambispective Cohort Study

The main aim of this study is to compare the HAE attack rate requiring on-demand treatment before and within 2 years after participants with HAE have been treated with lanadelumab.

This study is conducted in the United Kingdom where participants were treated or about to be treated with landelumab according to their routine practice at hospitals. Data will be directly collected from participants via study diaries, questionnaires, their medical records, and study doctors treating them. Participants will be contacted every 3 months during study participation (via phone).

Study Overview

• Status: Recruiting
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Other: No Intervention

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Takeda Contact; Phone Number: +1-877-825-3327; Email: medinfoUS@takeda.com

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, E1 1BB
      • Recruiting
      • Barts Health NHS Trust
      • Principal Investigator: Sorena Kiani-Alikhan, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The population of this survey is all participants with HAE type I or II treated with lanadelumab in hospitals within the UK.

Description

Inclusion:

• Documented diagnosis of HAE type I or II (confirmed through laboratory testing)
• Documented initiation of treatment with lanadelumab
• Greater than or equal to (≥)12 years of age at initiation of treatment with lanadelumab
• ≥12 months of continuous medical record data before initiation of treatment with lanadelumab

Exclusion:

• Exposure to lanadelumab administered as an investigation product in a clinical trial setting at any point in time

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prevalent Cohort A; Prevalent Cohort A will comprise eligible participants with HAE type I or II who have initiated treatment with lanadelumab at any point in time (i.e., all prevalent cases of exposure to lanadelumab). The total follow-up encompasses a 12-month pre-treatment period, and an up-to 24-month post-treatment period.	Other: No Intervention; As it is an observational study, no intervention is administered in this study.
Prevalent Cohort B; Prevalent Cohort B will comprise eligible participants with HAE type I or II who have been treated with lanadelumab for <12 months (i.e., the subset of participants from Prevalent Cohort A who initiated treatment with lanadelumab within <12 months). The total follow-up encompasses a 12-month pre-treatment and an up to 24-month post-treatment period, as well as a prospective data collection period of participant-specific duration.	Other: No Intervention; As it is an observational study, no intervention is administered in this study.
Incident Cohort A; Incident Cohort A will comprise eligible participants with HAE type I or II initiating treatment with lanadelumab at any time within the prospective data collection time period. The total follow-up encompasses a 12-month pre-treatment and an up-to 24-month post-treatment period, as well as a prospective data collection period of participant-specific duration.	Other: No Intervention; As it is an observational study, no intervention is administered in this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Hereditary Angioedema (HAE) Attacks Requiring On-demand Treatment	Number of HAE attacks requiring on-demand treatment before and after the index date (lanadelumab treatment initiation day) will be reported.	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Categorized by Their Demographic Characteristics	Demographic characteristics will include age, sex, and ethnic group at index.	At index (lanadelumab treatment initiation day)
Number of Participants Categorized by Their Clinical Characteristics	Clinical characteristics will include categories of participant-reported age at onset of symptoms, age at diagnosis of HAE, duration of time from onset to diagnosis (i.e., the diagnostic delay), body mass index (BMI) (at index); comorbidities (pre and post index), history of laryngeal attacks (pre index), type of HAE (type I and II), and triggers for HAE symptoms onset (at index and post index). Index is defined as the lanadelumab treatment initiation day.	Up to approximately 3 years
Number of Participants Categorized by Their Treatment Patterns	Treatment patterns will include categories of the summary of participant-reported duration of lanadelumab treatment, treatment dose given to participants, and participant with switching patterns with lanadelumab on occurence of HAE attacks.	At and after index (lanadelumab treatment initiation day plus approximately 2 years)
Number of Participants Categorized by Their Patterns of Prophylactic Treatment	Patterns of prophylactic treatment will include categories of the summary of participant-reported use of brand and drug name, duration of treatment, dose of the treatment within same class of prophylactic treatments.	Up to approximately 3 years
Number of Participants Categorized by Their Clinical Features of HAE Attacks Requiring On-Demand Treatment	Clinical features of HAE attacks requiring on-demand treatment will include categories of summary of participant-reported time of attack, duration of attack, location (e.g., trunk, extremities, and larynx) of HAE attack, the severity (Grade 1 [Mild], Grade 2 [Moderate], and Grade 3 [Severe]) of HAE attack, and hospitalization due to the HAE attack.	Up to approximately 3 years
Number of Self-Reported HAE Attacks		Up to approximately 3 years
Number of Participants Categorized by Their Clinical Features of Self-Reported HAE Attacks	Clinical features of self-reported HAE attacks will include categories of summary of participant-reported time of attack, duration of attack, location (e.g., trunk, extremities, and larynx) of HAE attack, the severity (Grade 1 [Mild], Grade 2 [Moderate], and Grade 3 [Severe]) of HAE attack, symptoms of HAE attack (e.g., tiredness, abdominal pain, and abdominal swelling), and identified or suspected trigger(s) for the attack (e.g., contact with chemicals, drugs, or foods).	Up to approximately 3 years
European Quality of Life 5 Dimensions 3-levels (EQ-5D-3L) Questionnaire Total Score	The EQ-5D-5L questionnaire will be used to record impact of HAE on participant's quality-of-life (QoL). The EQ-5D-5L is a descriptive system of Health-Related Quality-of-Life (HRQoL) states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can take 1 of 5 responses. The responses record 5 levels of severity [no problems, slight problems, moderate problems, severe problems, and extreme problems] within a particular dimension. The scores will be the sum of scores from each dimension and can range from 5 (no problems) to 25 (extreme problems). Higher score indicated a worsening health condition.	Up to approximately 2 years
EQ-5D-3L Visual Analogue Scale (VAS) Score	The EQ-5D-3L VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS is used as a quantitative measure of health outcome that reflect the participant's own judgement score, with a score of 0 as the worst and 100 as the best possible health.	Up to approximately 2 years
Angioedema Quality of Life (AE-QoL) Total Scores	AE-QoL is a self-administered instrument designed to measure HRQoL in adult participants with HAE type I and II. The AE-QoL consists of 17 disease-specific quality-of-life items, to produce a total AE-QoL score and 4 domain scores (functioning, fatigue/mood, fears/shame, and food, Each of the 17 items has a five-point response scale ranging from 1 (Never) to 5 (Very Often).	Up to approximately 2 years
Angioedema Quality of Life (AE-QoL) Domain Scores	AE-QoL is a self-administered instrument designed to measure HRQoL in adult participants with HAE type I and II. The AE-QoL consists of 17 disease-specific quality-of-life items, to produce a total AE-QoL score and 4 domain scores (functioning, fatigue/mood, fears/shame, and food, Each of the 17 items has a five-point response scale ranging from 1 (Never) to 5 (Very Often).	Up to approximately 2 years
Number of Participants With HAE-related Health Care Resource Utilization (HCRU)	Healthcare resources used during medical encounters include in and out-patient visits to physicians, hospital admissions, in and out-patient emergency care, and in and out-patient clinical examinations and tests.	Up to approximately 3 years
Angioedema Control Test (AECT) Total Score	The AECT is used to assess participants with recurrent angioedema. The test uses a questionnaire with 4 items, each of which has 5 options and is used to measure the participant's current disease control. HAE control score will be recorded with 5 levels of answers [1=very often, 2=often, 3=sometimes, 4=seldom, 5=not at all] to the following questions: 1) In the last 3 months, how often have you had angioedema? 2) In the last 3 months, how much has your QoL been affected by angioedema? 3) In the last 3 months, how much has the unpredictability of your angioedema bothered you? 4) In the last 3 months, how well has your angioedema been controlled by your therapy?	Up to approximately 2 years
Angioedema Control Test (AECT) Domain Score	The AECT is used to assess participants with recurrent angioedema. The test uses a questionnaire with 4 items, each of which has 5 options and is used to measure the participant's current disease control. HAE control score will be recorded with 5 levels of answers [1=very often, 2=often, 3=sometimes, 4=seldom, 5=not at all] to the following questions: 1) In the last 3 months, how often have you had angioedema? 2) In the last 3 months, how much has your QoL been affected by angioedema? 3) In the last 3 months, how much has the unpredictability of your angioedema bothered you? 4) In the last 3 months, how well has your angioedema been controlled by your therapy?	Up to approximately 2 years
Treatment Satisfaction Questionnaire for Medication (TSQM) Total Score	The TSQM comprises 14 items across four domains focusing on effectiveness (three items), side effects (five items), convenience (three items), and global satisfaction (three items) of the medication over the previous 2-3 weeks, or since the patient's last use. With the exception of item 4 (presence of side effects; yes or no), all items have five or seven responses, scored from one (least satisfied) to five or seven (most satisfied). The 7-item scales had a non-neutral midpoint, such that there were more positive response options than negative response options, to allow for precise information to be obtained at the upper end of the score distribution. Item scores are summed to give four domain scores, which are in turn transformed to a scale of 0-100.	Up to approximately 2 years
Treatment Satisfaction Questionnaire for Medication (TSQM) Domain Score	The TSQM comprises 14 items across four domains focusing on effectiveness (three items), side effects (five items), convenience (three items), and global satisfaction (three items) of the medication over the previous 2-3 weeks, or since the patient's last use. With the exception of item 4 (presence of side effects; yes or no), all items have five or seven responses, scored from one (least satisfied) to five or seven (most satisfied). The 7-item scales had a non-neutral midpoint, such that there were more positive response options than negative response options, to allow for precise information to be obtained at the upper end of the score distribution. Item scores are summed to give four domain scores, which are in turn transformed to a scale of 0-100.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2023
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): October 30, 2025

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: TAK-743-0001; MACS-2021-0616012 (Other Identifier: Takeda)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No