Non-inferiority study of GSK3511294 (depemokimab) compared with mepolizumab or benralizumab in participants with severe asthma with an eosinophilic phenotype

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

28 May 2021 → 14 Sep 2025

Decision date (initial)

2024-06-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GlaxoSmithKline Research & Development Limited

External identifiers

EU CT number

2023-510230-84-00

EudraCT number

2020-003612-28

ClinicalTrials.gov

NCT04718389

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of GSK3511294 100 mg (SC) every 26 weeks versus maintaining existing treatment with either mepolizumab or benralizumab in participants with severe asthma with an eosinophilic phenotype who have previously benefited from anti-IL-5/5R therapy

Secondary objectives 1

1. To evaluate GSK3511294 100 mg (SC) every 26 weeks versus maintaining existing treatment with either mepolizumab or benralizumab on health related quality of life (HRQoL) and additional efficacy assessments

Conditions and MedDRA coding

Severe asthma with an eosinophilic phenotype

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-002836-PIP01-20

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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] Note for Germany, UK and Norway Participants: In Germany, UK and Norway, only adult participants (≥18 years) are to be included in this clinical trial. Note for Austrian Participants: In Austria, participants who are ≥16 years are to be included in this clinical trial.
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 1 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 to or a beneficiary of a social security category.

Exclusion criteria 18

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.
10. Other mAbs used in the treatment of asthma: Participants who have received omalizumab (Xolair), dupilumab (Dupixent), reslizumab (Cinqair/Cinqaero) or Tezepelumab (Tezspire) 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. Authorised treatments for COVID-19 are permitted and should be used in line with local regulatory guidance.
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.
13. ECG Assessment: QTcF ≥450msec or QTcF ≥480 msec for participants with Bundle Branch Block in the central over-read 12-lead ECG at screening Visit 1.
14. Smoking history: Current smokers or former smokers with a smoking history of ≥20 pack years (number of pack years = (number of cigarettes per day / 20) x number of years smoked). Pipes and/or cigars and/or electronic cigarettes/vaping use cannot be used to calculate pack-year history. Current and former use of these is exclusionary.
15. Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
16. Hypersensitivity: Participants with allergy/intolerance to a mAb or biologic or any of the excipients of the investigational products listed in section 6.1 of the protocol.
17. Pregnancy: Participants who are pregnant or breastfeeding.
18. Adherence: Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualised rate of clinically significant exacerbations over 52 weeks

Secondary endpoints 3

1. Weighted mean change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score calculated over 52 weeks
2. Weighted mean change from baseline in Asthma Control Questionnaire-5 (ACQ-5) score calculated over 52 weeks
3. Weighted mean change from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) calculated over 52 weeks

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 4

Locations

12 EU/EEA countries · 118 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 239 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications