A 52-week study to evaluate, monitor, and compare disease worsening and safety in adult and adolescent participants with severe eosinophilic asthma receiving GSK3511294, Benralizumab, or Mepolizumab.
Zusammenfassung der Studie
GSK3511294 is a drug known as a monoclonal antibody that is manufactured in the laboratory. It blocks a specific protein (protein) in the body that is involved in the severity of asthma and pneumonia. This clinical study investigates whether GSK3511294 (referred to as the "investigational drug") works as well as the medications you have used to treat your condition (Mepolizumab or Benralizumab). The study also examines whether the investigational drug is safe and has side effects. The investigational drug works similarly to 3 already approved medications: Mepolizumab, Reslizumab, and Benralizumab. These medications are administered every 4 to 8 weeks. However, there is hope that the effect of the investigational drug will last longer (administered once every 26 weeks). All study participants receive treatment with an active ingredient, either the investigational drug or the comparator drug. Their assignment to one of the groups is done by a computer. Since there are only two groups, you can think of this assignment like flipping a coin. This means that your chance of being assigned to one of the two groups is equal. Neither the investigator, the study staff, nor you know which treatment you are receiving. This is to ensure that the results of the two groups being studied are treated in the same way. In the event of a medical emergency - whether or not related to the clinical study - your group assignment can be determined to obtain information about the treatment you received during the study. The main goal of the genetic research part of this study is to understand eosinophilic asthma, related conditions, and how people respond to the treatments used in the study. This is done by examining your DNA.
(BASEC)
Untersuchte Intervention
In this study, the investigational drug is compared either to Mepolizumab or Benralizumab, which act as comparator drugs. The effects of the medications - both good and bad - are compared. Study participants are divided into two groups to receive:
1. Investigational drug (once every 26 weeks) + Placebo (once every 4 or 8 weeks)
2. Mepolizumab (once every 4 weeks) or Benralizumab (once every 8 weeks) + Placebo (once every 26 weeks)
A placebo looks just like the investigational drug and the comparator drug, but does not contain the active ingredient that may help your asthma.
All study participants receive treatment with an active ingredient. They receive either the investigational drug or the comparator drug (Mepolizumab or Benralizumab) that they used before the study. No participant who has previously used Mepolizumab will be assigned to Benralizumab, and no participant who has previously used Benralizumab will be assigned to Mepolizumab.
Throughout the study, you will continue to use your usual asthma medications (except Mepolizumab or Benralizumab). The investigator will tell you more about the medications that are allowed during the study. The investigator will provide emergency medications (inhalers like Albuterol/Salbutamol) that can be used if your symptoms worsen at any time during the study.
The investigational drug, the comparator drug, and the placebo (collectively referred to as "study medication") will be administered by injection under the skin. This is known as a subcutaneous (s.c.) injection. The investigational drug is available in pre-filled safety syringes. This means that the injections are ready to use and require no further preparation.
(BASEC)
Untersuchte Krankheit(en)
GSK3511294 is currently being tested as a potential new drug for severe asthma and is not yet approved for the treatment of patients with asthma.
(BASEC)
1. Male or suitable female adults or adolescents aged at least 12 years who are able to sign a consent form, which also includes adherence to the study's requirements and restrictions. Female participants must not be pregnant or breastfeeding. Women of childbearing potential must use highly effective contraceptive methods. 2. Only individuals with a documented asthma diagnosis for at least 2 years can participate in this study. The asthma diagnosis must comply with the guidelines of the National Heart, Lung, and Blood Institute (NHLBI) or the so-called GINA guidelines (The Global Initiative for Asthma). This asthma diagnosis must have been regularly treated in the last 12 months with a medium to high dose (at least 440 micrograms per day) of inhaled corticosteroids with or without maintenance therapy with oral corticosteroids. 3. Individuals who have received either 100 mg of Mepolizumab or 30 mg of Benralizumab for at least 12 months prior to the first examination for this study. The patient must have responded to treatment with Mepolizumab or Benralizumab as follows: at least 50% reduction in exacerbation frequency since the start of treatment OR at least 50% reduction in the use of oral corticosteroids for maintenance therapy since the start of treatment OR no deterioration of the condition in the last 6 months during treatment with Mepolizumab or Benralizumab and ACQ-5 score of ≤ 1.5 at the pre-examination. (BASEC)
Ausschlusskriterien
1. Health conditions: The person must not have any other pre-existing clinically relevant lung disease other than asthma. This includes (but is not limited to) current infections, chronic bronchitis, or a history of lung cancer. Other conditions leading to exclusion include diseases that may cause increased eosinophils, a pre-existing parasitic infestation, immunodeficiency (e.g., HIV), a current malignancy, or a history of cancer in remission for less than 12 months, a current unstable liver or gallbladder disease, an active COVID-19 infection, or a known allergy/intolerance to the treatment. 2. Previous or concomitant therapies: Individuals treated with other asthma treatments such as Omalizumab, Dupilumab, or Reslizumab will be excluded under certain circumstances. Additionally, individuals must be excluded if they have been treated with an investigational drug within the last 30 days prior to this study. 3. Individuals who are currently smokers or former smokers and have a history of alcohol or drug abuse will be excluded under certain circumstances. (BASEC)
Studienstandort
Aarau, Basel, St Gallen
(BASEC)
Sponsor
GlaxoSmithKline Research & Development Limited, UK Kantonsspital Baselland - Standort Liestal
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Dr. Joerg Leuppi
+41619252180
joerg.leuppi@clutterksbl.chKantonsspital Baselland - Standort Liestal
(BASEC)
Allgemeine Auskünfte
GlaxoSmithKline
(ICTRP)
Wissenschaftliche Auskünfte
GlaxoSmithKline
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Nordwest- und Zentralschweiz EKNZ
(BASEC)
Datum der Bewilligung durch die Ethikkommission
29.09.2021
(BASEC)
ICTRP Studien-ID
NCT04718389 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
A 52-week, randomised, double-blind, double-dummy, parallel group, multicentre, non-inferiority study assessing exacerbation rate, additional measures of asthma control and safety in adult and adolescent severe asthmatic participants with an eosinophilic phenotype treated with GSK3511294 compared with mepolizumab or benralizumab (BASEC)
Wissenschaftlicher Titel
A 52-week, Randomised, Double-blind, Double-dummy, Parallel Group, Multi-centre, Non-inferiority Study Assessing Exacerbation Rate, Additional Measures of Asthma Control and Safety in Adult and Adolescent Severe Asthmatic Participants With an Eosinophilic Phenotype Treated With GSK3511294 Compared With Mepolizumab or Benralizumab (ICTRP)
Öffentlicher Titel
A Study of GSK3511294 (Depemokimab) Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype (ICTRP)
Untersuchte Krankheit(en)
Asthma (ICTRP)
Untersuchte Intervention
Biological: GSK3511294 (Depemokimab)Biological: MepolizumabBiological: BenralizumabBiological: PlaceboDrug: Standard of care (SoC)Device: Pre-filled Syringes (PFS) (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator). (ICTRP)
Ein-/Ausschlusskriterien
Key inclusion criteria for study:
- Adult and adolescent participants more than or equal to (>=)12 years of age, at the
time of signing the informed consent/assent.
- Participants who have a documented physician diagnosis of asthma for >=2 years that
meets the National Heart, Lung, and Blood Institute guidelines (NHLBI) or Global
Initiative for Asthma (GINA) guidelines.
- Participants receiving either mepolizumab 100 milligrams (mg) or benralizumab 30 mg
for >=12 months prior to screening and have a documented benefit to therapy assessed
by either:
(i) >=50% reduction in exacerbation frequency since initiating treatment, or (ii)
>=50% reduction in maintenance OCS use since initiating treatment, or (iii) No
exacerbations in the past 6 months whilst receiving anti-IL-5/5R therapy and an
Asthma Control Questionnaire (ACQ)-5 score of less than or equal to (<=)1.5 at
screening.
- A well-documented requirement for regular treatment with medium to high dose ICS in
the 12 months prior to Visit 1 with or without maintenance OCS. The maintenance ICS
dose must be >=440 micrograms (mcg) fluticasone propionate (FP) hydrofluoroalkane
(HFA) product daily, or clinically comparable. Participants who are treated with
medium dose ICS will also need to be treated with a LABA to qualify for inclusion.
- Current treatment with at least one additional controller medication, besides ICS
[for example (e.g.), LABA, LAMA, leukotriene receptor antagonist (LTRA), or
theophylline].
Key exclusion criteria for study:
- Participants with presence of a known pre-existing, clinically important lung
condition other than asthma. This includes (but is not limited to) current
infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or
diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease
other than asthma) or a history of lung cancer.
- Participants with other conditions that could lead to elevated eosinophils such as
hyper-eosinophilic syndromes including (but not limited to) Eosinophilic
Granulomatosis with Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome) or
Eosinophilic Esophagitis.
- A current malignancy or previous history of cancer in remission for less than 12
months prior to screening (Participants that had localized carcinoma of the skin
which was resected for cure will not be excluded).
- Cirrhosis or current unstable liver or biliary disease per investigator assessment
defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia,
esophageal or gastric varices, persistent jaundice.
- Participants with current diagnosis of vasculitis. Participants with high clinical
suspicion of vasculitis at screening will be evaluated and current vasculitis
excluded prior to enrolment.
- Participants who have received Omalizumab (Xolair), dupilumab (Dupixent) or
reslizumab (Cinqair/Cinqaero) within 130 days prior to Visit 1.
- Participants who have received any Monoclonal antibody (mAb) within 5 half-lives of
Visit 1.
- Corrected QT interval using Fridericia's formula (QTcF) >=450 milliseconds (msec) or
QTcF >=480 msec for participants with Bundle Branch Block at screening Visit 1.
- Current smokers or former smokers with a smoking history of >=10 pack years (number
of pack years equal to [number of cigarettes per day/20] times number of years
smoked). A former smoker is defined as a participant who quit smoking at least 6
months prior to Visit 1.
- Participants with allergy/intolerance to a mAb or biologic.
Key exclusion criteria for randomization:
- Evidence of a clinically significant abnormality in the 12-lead electrocardiogram
(ECG) over-read conducted at Screening Visit 1, based on the evaluation of the
investigator, or QTcF >=450 msec or QTcF >=480 msec for participants with Bundle
Branch Block, at randomization Visit 2.
- Participants with a clinically significant asthma exacerbation in the 7 days prior
to randomization should have their randomization visit delayed until the
investigator considers the participant's asthma to be stable. If the 8-week
screening period has elapsed, then the participant should be considered a run-in
failure.
- Any changes in the dose or regimen of Baseline ICS and/or additional controller
medication (except for treatment of an exacerbation) during the run-in period. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Annualized rate of clinically significant exacerbations over 52 weeks (ICTRP)
Weighted mean change from Baseline in St. George's Respiratory Questionnaire (SGRQ) total score;Weighted mean change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score;Weighted mean change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
Iqvia Pty Ltd (ICTRP)
Weitere Kontakte
GSK Clinical Trials, GlaxoSmithKline (ICTRP)
Sekundäre IDs
206785 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT04718389 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar