Placebo-controlled efficacy and safety study of GSK3511294 in participants with severe asthma with an eosinophilic phenotype
- Conditions
- Severe uncontrolled asthma with an eosinophilic phenotypeMedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2020-003611-10-IT
- Lead Sponsor
- GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 375
1. Age: Adults and adolescents =12 years of age, at the time of signing
the informed consent/assent. [For countries where local regulations or
the regulatory status of study medication permit enrolment of adults
only, participants recruited will be =18 years of age]
2. Asthma: Participants must have a documented physician diagnosis of
asthma for =2 years that meets the National Heart, Lung, and Blood
Institute guidelines [NHLBI, 2007] or GINA guidelines [GINA, 2020]
AND
a) Eosinophilic phenotype: Have, or with high likelihood of having,
asthma with an eosinophilic phenotype as per Randomisation Criteria 1
and 2 (see Section 5.3 of the protocol)
AND
b) Exacerbation history: Have previously confirmed history of =2
exacerbations requiring treatment with systemic corticosteroids ( CS)
(IM, IV, or oral), in the 12 months prior to Visit 1, despite the use of
medium to high-dose inhaled corticosteroids (ICS) (see criterion 4). For
participants receiving maintenance CS, the CS treatment for the
exacerbations must have been a two-fold dose increase or greater.
3. Airflow obstruction: Persistent airflow obstruction as indicated by:
a) For participants =18 years of age at Visit 1, a pre-bronchodilator FEV1
<80% predicted (NHANES III) recorded at Visit 1
b) For participants 12-17 years of age at Visit 1:
• A pre-bronchodilator FEV1 <90% predicted (NHANES III) recorded at
Visit 1 OR
• FEV1:Forced Vital Capacity (FVC) ratio <0.8 recorded at Visit 1
4. Inhaled Corticosteroid: 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 mcg FP HFA daily, or clinically comparable [GINA, 2020; see
Appendix 10 of the protocol]. Participants who are treated with medium
dose ICS will also need to be treated with Long-acting beta-agonist
(LABA) to qualify for inclusion.
5. Additional Controller Medication: Current treatment with at least one
additional controller medication, besides ICS, for at least 3 months [e.g.,
LABA, long-acting muscarinic antagonist (LAMA), leukotriene receptor
antagonist (LTRA), or theophylline].
6. Male or eligible female.
• A female participant is eligible to participate if she is not pregnant or
breastfeeding, and one of the following conditions applies:
o Is a woman of non-childbearing potential (WONCBP) as defined in
Section 10.4.1 of the protocol
OR
Is a woman of childbearing potential (WOCBP) and using a contraceptive
method that is highly effective, with a failure rate of <1%, as described
in Section 10.4.2 of the protocol from at least 14 days prior to the first
dose of study intervention until at least 30 weeks after the last
administered dose of study intervention.
•A WOCBP must have a negative highly sensitive serum pregnancy test
at screening Visit 1 and a negative highly sensitive urine pregnancy test
within 24 hours before the first dose of study intervention. Additional
requirements for pregnancy testing during and after study intervention
are located in Section 8.3.5. of the protocol
•Contraceptive use by women should be consistent with local
regulations regarding the methods of contraception for those
participating in clinical studies.
• The investigator should evaluate the potential for contraceptive
method failure (e.g., noncompliance, recently initiated in relationship to
the first dose of study intervention).
• The investigator is responsible for review of medical history, menstrual
hist
1. Concurrent Respiratory Disease: 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.
2. Eosinophilic Diseases: Participants with other conditions that could
lead to elevated eosinophils such as hyper-eosinophilic syndromes
including (but not limited to) Eosinophilic Granulomatosis with
Eosinophilic Esophagitis.
3. Parasitic infection: Participants with a known, pre-existing parasitic
infestation within 6 months prior to Visit 1.
4. Immunodeficiency: A known immunodeficiency (e.g. human
immunodeficiency virus – HIV), other than that explained by the use of
CSs taken as therapy for asthma.
5. Malignancy: A current malignancy or previous history of cancer in
remission for less than 12 months prior to screening (Participants that
had localised carcinoma of the skin which was resected for cure will not
be excluded).
6. Liver Disease: Cirrhosis or current unstable liver or biliary disease per
investigator assessment defined by the presence of ascites,
encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or
gastric varices, persistent jaundice.
NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert's
syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C)
are acceptable if participant otherwise meets entry criteria.
7. Other Concurrent Medical Conditions: Participants who have known,
preexisting, clinically significant cardiac, endocrine, autoimmune,
metabolic, neurological, renal, gastrointestinal, hepatic, haematological
or any other system abnormalities that are uncontrolled with standard
treatment.
8. Vasculitis: Participants with current diagnosis of vasculitis.
Participants with high clinical suspicion of vasculitis at screening will be
evaluated and current vasculitis must be excluded prior to enrolment.
9. COVID-19: Participants that, according to the investigator's medical
judgment, are likely to have active COVID-19 infection should be
excluded. Participants with known COVID-19 positive contacts within the
past 14 days should be excluded for at least 14 days following the
exposure during which the participant should remain symptom-free.
10. Monoclonal antibodies targeting IL-5/5R: Participants who have
received mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), or
benralizumab (Fasenra) within 12 months prior to Visit 1 or who have a
previous documented failure with anti-IL-5/5R therapy.
11. Other mAbs in the treatment of asthma: Participants who have
received omalizumab (Xolair) or dupilumab (Dupixent) within 130 days
prior to Visit 1.
12. Other mAbs not used for the treatment of asthma: Participants who
have received any mAb within 5 half-lives of Visit 1.
13. Investigational Medications: Participants who have received
treatment with an investigational drug within the past 30 days or five
terminal phase half-lives of the drug whichever is longer, prior to Visit 1
(this also includes investigational formulations of marketed products).
14. Previous participation: Previously participated in any study with
mepolizumab, reslizumab, or benralizumab and received study
intervention (including placebo) within 12 months prior to Visit 1.
15. ECG Assessment: QTcF =450 msec or QTcF =480 msec for
participants wit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method