Real-life First Dose Effect of Fasenra in Patients With Severe Uncontrolled Asthma (TWINKLE)

This pilot study will use novel technologies to collect information about the patient experience before and early after starting Fasenra (benralizumab) as standard of care for severe uncontrolled asthma in a real-world setting, to determine how the experience changes over time. Any detection of an early, subjective first-dose effect in this pilot study will be further validated in a larger follow-up study.

Study Overview

• Status: Completed
• Conditions: Severe Uncontrolled Asthma

Detailed Description

PRIMARY OBJECTIVE: Explore the use of novel technologies to detect early changes in quality of life (QoL) within the first 4 weeks after first dose of Fasenra for the treatment of severe uncontrolled asthma.

ENDPOINTS: Improvement in QoL measures, and physical and mental well-being as assessed by an increase in positive facial expressions, positive keywords, and quality of life biomarkers, with a decrease in asthma symptoms and improvement in FEV1 and PEF within the first 4 weeks after beginning Fasenra.

TARGET POPULATION: Individuals aged 18-75 years with severe asthma uncontrolled (ACQ >=1.5) on current medications (HD-ICS/LABA with/without other maintenance therapies except biologics). Patients beginning Fasenra asstandard of care as specified by NICE guidelines.

STUDY DURATION: The study duration per patient will be approximately 6 weeks from the enrolment visit to end of recorded data. Subjects will record data for 2 weeks prior to their first injection with Fasenra and then for 4 more weeks post-injection. PROCEDURESPatients will be required to visit the study site 3 times (enrolment and onboarding visit, Fasenra injection visit, last visit), and perform daily tasks at home in between site visits

• Study Type: Observational
• Enrollment (Actual): 5

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals aged 18-75 years with severe asthma uncontrolled (ACQ >=1.5) on current medications (HD-ICS/LABA with/without other maintenance therapies except biologics) who are beginning Fasenra treatment as standard of care.

Description

Inclusion Criteria:

• Individuals aged 18-75 years with severe asthma uncontrolled (ACQ >=1.5) on current medications (HD-ICS/LABA with/without other maintenance therapies except biologics).
• Patients beginning Fasenra as standard of care as specified by NICE guidelines. That is, patients having either 4 exacerbations in the previous year and an eosinophil count over 300 cells/ microliter OR 3 exacerbations in the previous year and an eosinophil count over 400 cells/ microliter.
• Provision of informed consent prior to any study specific procedures
• Patients must have a smartphone that is compatible with the device software (iOS and Android).
• Availability of, and willingness to use, without reimbursement of any potential additional costs incurred, their computer and/or iOS/Android device for the collection and transmission of information
• English speaking and reading (ability to understand ICF, patient materials, the study app and to interact with the onboarding agent).

Exclusion Criteria:

• Patients taking daily prednisolone (or equivalent)
• Patients currently taking a biologic medication or participating in a clinical study involving a biologic medication for a respiratory illness.
• Comorbid conditions that cause symptoms similar to those experienced with asthma (e.g./ cough, wheeze, breathlessness, or nighttime awakening).
• Patients with comorbidities that also significantly affect patient's quality of life and daily functioning as determined by the treating physician.
• Presence of other chronic pulmonary conditions (e.g./ COPD)
• Patients that in the opinion of the physician are unlikely to complete 6 weeks of the study (example reasons: digital literacy, unwillingness/inability to interact with apps; historically poor adherence to study procedures)

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sentiment score	Evaluate if the PROACT system can detect early signs of changes in quality of life (QoL) using sentiment analysis to determine changes in peoples' emotions as a subjective measure of first-dose effects of a medication. the score should be the positivity of the expression, scaled from 0 (the most negative) to 1.0 (totally positive).	6 weeks from baseline
Emotion confidence score	Evaluate if the PROACT system can detect early signs of changes in quality of life (QoL) using emotion confidence score to determine changes in peoples' emotions as a subjective measure of first-dose effects of a medication. Emotion confidence score should be the confidence (probability) of the predicted emotion given by the machine learning model. The scores will be scaled proportionally to have a sum of 1.0 for each frame of the video.	6 weeks from baseline
Key phrase extraction	Evaluate if the PROACT system can detect early signs of changes in quality of life (QoL) using key phrase extraction to determine changes in peoples' emotions as a subjective measure of first-dose effects of a medication. Key phrase extraction is a descriptive summary of the video message recorded.	6 weeks from baseline
Message analysis	Evaluate if the PROACT system can detect early signs of changes in quality of life (QoL) using message analysis to determine changes in peoples' emotions as a subjective measure of first-dose effects of a medication. The message analysis will define: The topic - what it is that the participant is trying to share. This is coded using an evolving, hierarchical, lexicon. The impact - if reported, the impact that this is having on the participant is also coded. An interpreted impact color scale (green-amber-red) is also applied by the analysts to aid quick identification of the most, and least, impactful things. The outcome - if reported, what the person did as a result of what happened. This is also coded so that it can also be aggregated across patients.	6 weeks from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PEF	Association between any onset of effect seen for PROACT measures and lung function (PEF, Peak Expiratory Flow) measurements. it can either be measured in L/sec or L/min .	6 weeks
FEV1	Association between any onset of effect seen for PROACT measures and lung function (FEV1, Forced Expiratory Volume in 1 Second) measurements. Measured in liters.	6 weeks
FEV1/FVC	Association between any onset of effect seen for PROACT measures and lung function (FEV1/FVC (forced vital capacity), ratio of FEV1 to FVC ) measurements. Can be expressed as a percentage or ratio.	6 weeks
ACQ-6 Score	Association between any onset of effect seen for PROACT measures and PRO ACQ-6, using the ACQ-6 score. Patients are asked to recall how their asthma has been during the previous week by responding to 6 questions. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and <1.5 indicate partly controlled asthma, and a score ≥1.5 indicates not well-controlled asthma.	6 weeks
SGRQ Score	Association between any onset of effect seen for PROACT measures and PRO SQRQ, using the SGRQ Score. The SGRQ is a 50-item PRO instrument developed to measure the health status of patients with airway obstruction diseases. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ yields a total score and 3 domain scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment.	4 weeks from Fasenra injection
daily UMotif measure	Association between any onset of effect seen in the daily uMotif measures and the ACQ-6 and SQRQ/lung function measurements will be assessed. The UMotif Quality of Life questionnaire consists of 10 separate 5 point Likert scale questions. Of these, 8 are required questions, and the remaining 2 are chosen at enrolment by patients from a choice of 4 possible questions. Responses to each of these questions will be compared to their own baseline at enrolment to derive personalized metrics. A composite metric will also be created by appropriately combining the individual question responses. The required 8 questions will be summarized descriptively by day. The 2 optional questions that patients report daily will be reported descriptively.	6 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Lynn Hagger, Astra Zeneca R&D

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2019
• Primary Completion (Actual): April 9, 2020
• Study Completion (Actual): April 9, 2020

Study Registration Dates

• First Submitted: November 5, 2019
• First Submitted That Met QC Criteria: December 13, 2019
• First Posted (Actual): December 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: D3250R00061

Drug and device information, study documents

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