| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Severe asthma with an eosinophilic phenotype |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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 |
|
| E.2.2 | Secondary objectives of the trial |
| 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 to or a beneficiary of a social security category. |
|
| E.4 | Principal 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 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.
17. Pregnancy: Participants who are pregnant or breastfeeding. Participants should not be enrolled if they plan to become pregnant during the time of study participation. Requirements for pregnancy testing are located in Section 8.3.5 of the protocol.
18. Adherence: Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Annualised rate of clinically significant exacerbations over 52 weeks |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.Week 0 through Week 52
2.Week 0 through Week 52
3.Week 0 through Week 52 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Double dummy design to maintain the blind |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 185 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Switzerland |
| Puerto Rico |
| Taiwan |
| Australia |
| Canada |
| Japan |
| United Kingdom |
| United States |
| Austria |
| Belgium |
| Czechia |
| Finland |
| France |
| Germany |
| Hungary |
| Ireland |
| Italy |
| Netherlands |
| Norway |
| Poland |
| Portugal |
| Slovenia |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 5 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 5 |
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