on-inferiority study of GSK3511294 compared with mepolizumab or benralizumab in participants with severe asthma with an eosinophilicphenotype

Phase 1

Conditions: Severe asthma with an eosinophilic phenotype
MedDRA version: 20.0Level: SOCClassification code 10038738Term: Respiratory, thoracic and mediastinal disordersSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2020-003612-28-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: 1700

Inclusion Criteria

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 who 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].
3. Anti-IL-5/5R Therapy: Receiving either mepolizumab 100 mg SC or
benralizumab 30 mg SC for =12 months prior to Screening and have a
documented benefit to therapy assessed by either:
• =50% reduction in exacerbation frequency since initiating treatment,
OR
• =50% reduction in maintenance OCS use since initiating treatment, OR
• no exacerbations in the past 6 months whilst receiving anti-IL-5/5R
therapy and an ACQ-5 score of =1.5 at Screening.
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 fluticasone propionate [FP] hydrofluoroalkane product [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 a Long-acting beta-agonist (LABA) to qualify for
inclusion.
5. Additional Controller Medication: Current treatment with at least one
additional controller medication, besides ICS
[e.g., LABA, 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
o 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 either: the first
dose (if study intervention was permanently discontinued prior to Week
26), or the dose at Week 26.
• 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
history, and recent sexual activity to decrease the risk for inclusion of a
woman with an early undetected pregnancy.
7. Informed Consent: Capable of giving signed informed consent/assent
as described in Section 10.1 of the protocol which includes compliance
with the requirements and restrictions listed in the informed consent
form (ICF) and in the protocol.
French participants: In France, a participant will be eligible for inclusion
in this study only if either affiliated

Exclusion Criteria

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
Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome) or
Eosinophilic Esophagitis.
3. Parasitic Infection: Participants with a known, pre-existing parasitic
infestation within 6 months prior to Visit 1 are to be excluded.
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 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. Other mAbs used in the treatment of asthma: Participants who have
received omalizumab (Xolair), dupilumab (Dupixent) or reslizumab
(Cinqair/Cinqaero) within 130 days prior to Visit 1.
11. Other mAbs not used for the treatment of asthma: Participants who
have received any mAb within 5 half-lives of Visit 1.
12. 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).
13. ECG Assessment: QTcF =450msec or QTcF =480 msec for
participants with Bundle Branch Block at screening Visit 1.
14. Smoking history: Current smokers or former smokers with a smoking
history of =10 pack years (number of pack years = (number of cigarettes
per day / 20) x number of years smoked). A former smoker is defined as
a participant who quit smoking at least 6 months prior to Visit 1.
15. Alcohol/Substance

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of GSK3511294 100 mg (SC) every 26 weeks<br>versus maintaining existing treatment with either mepolizumab<br>or benralizumab in participants with severe asthma with an eosinophilic<br>phenotype who have previously benefited from anti-IL-5/5R therapy;Secondary Objective: To evaluate GSK3511294 100 mg (SC) every 26 weeks versus<br>maintaining existing treatment with either mepolizumab or<br>benralizumab on health related quality of life (HRQoL) and additional<br>efficacy assessments;Primary end point(s): Annualised rate of clinically significant exacerbations over 52 week;Timepoint(s) of evaluation of this end point: Week 0 through Week 52

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1.Weighted mean change from baseline in St. George's Respiratory<br>Questionnaire (SGRQ) total score calculated over 52 weeks<br>2.Weighted mean change from baseline in Asthma Control<br>Questionnaire-5 (ACQ-5) score calculated over 52 weeks<br>3.Weighted mean change from baseline in pre-bronchodilator forced<br>expiratory volume in one second (FEV1) calculated over 52 we;Timepoint(s) of evaluation of this end point: 1.Week 0 through Week 52<br>2.Week 0 through Week 52<br>3.Week 0 through Week 52

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