| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10068462 |
| E.1.2 | Term | Eosinophilic 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 dexpramipexole on pulmonary function. |
|
| E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of dexpramipexole on asthma control, asthma symptoms, and quality of life.
•To evaluate the effect of dexpramipexole on blood eosinophils.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
To be eligible to participate in this study, candidates must meet the following eligibility criteria at the Screening Visit or at the time point specified in the individual eligibility criterion listed below:
1.Signed informed consent form.
2.Male or female ≥12 years of age at Screening Visit 1. Sites in Poland will only include participants aged ≥18 years.
Asthma-related criteria
3.Documented physician diagnosis of asthma for ≥12 months prior to Screening Visit 1.
4.Participants requiring at a minimum daily medium dose inhaled corticosteroids (ICS; ≥500 μg/day fluticasone propionate dry powder formulation daily or clinically comparable, per GINA 2021), plus one or more additional daily maintenance asthma controller medications, eg, long-acting β2 agonist (LABA), leukotriene antagonist, theophylline, long-acting muscarinic antagonists, cromolyn/nedocromil. Note: Poland will include participants requiring a minimum daily medium dose ICS (≥500 μg/day fluticasone propionate dry powder formulation daily or clinically comparable, per GINA 2021). Use of daily ICS must be for at least 12 weeks prior to Screening Visit 1 and the doses of all controller medications must be stable for at least 4 weeks prior to Screening Visit 1. Participants in Poland must be taking the equivalent of GINA Step 4 or 5 asthma controller medications.
The ICS may be contained within an ICS/ LABA combination product. As noted in Section 5.2.2, daily oral corticosteroids are an allowed concomitant medication.
5.Pre-BD FEV1 ≥40% and <80% (<90% for participants 12 to 17 years of age) of predicted at Screening Visit 2.
6.Bronchodilator reversibility, at Screening Visit 2 during screening, as evidenced by ≥12% and ≥200 mL improvement in FEV1, 15 to 30 minutes following inhalation of 400 µg (four puffs) of albuterol/salbutamol. Participants who do not meet the bronchodilator reversibility inclusion criterion (or have a history) but have ≥10% and ≥160 mL reversibility, may repeat the reversibility spirometry assessment once during the Screening Period, at an unscheduled visit prior to baseline.
7.ACQ-6 ≥1.5 at Screening Visit 2.
8.Eosinophil count of ≥0.30x10ˆ9/L at Screening Visit 1. May be repeated prior to or at Screening Visit 2 if the initial value is between 0.250x10ˆ9/L to 0.299x10ˆ9/L
General medical history
9.Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Screening and Baseline visits.
10.WOCBP must use either of the following methods of birth control, from Screening Visit 1 through the End of Study Visit:
a.A highly effective form of birth control (confirmed by the investigator). Highly effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective intrauterine device (IUD), IUD/intrauterine system (IUS), Levonorgestrel Intrauterine system, or oral contraceptive.
Or
b. Two protocol acceptable methods of contraception in tandem.
Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months prior to the planned date of the Baseline Visit without an alternative medical cause. The following age specific requirements apply:
c. Women <50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range.
d. Women ≥50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment. |
|
| E.4 | Principal exclusion criteria |
1.A participant who experiences a severe asthma exacerbation (defined
as a deterioration of asthma that results in emergency treatment,
hospitalization due to asthma, or treatment with systemic steroids) at
any time from 4 weeks prior to the SCR Visit 1 up to and including the
Baseline Visit.
Participants who experience an asthma exacerbation during the
Screening/Run-in Period may remain in screening and proceed with
study visits 14 days after they have completed their course of oral
steroids or returned to their pre-Screening visit maintenance dose of
oral steroids and the investigator considers participant has returned to
baseline status.
2.Current diagnosis of diseases which may confound interpretation of
this study's findings such as allergic bronchopulmonary aspergillosis,
eosinophilic granulomatosis with polyangiitis, eosinophilic
gastrointestinal diseases, hypereosinophilic syndrome, chronic
obstructive pulmonary disease, idiopathic pulmonary fibrosis.
3.Respiratory infection: Upper or lower respiratory tract, sinus, or middle
ear infection within the 4 weeks before SCR Visit 1.
Prohibited medications/procedures
4.Treatment with a biologic investigational drug in the last 5 months
prior to SCR Visit 1. Treatment with non-biologic investigational drugs in
the previous 30 days or five-half-lives prior to SCR Visit 1, whichever is
longer. Treatment with GSK3511294 (long-acting anti-interleukin-5) in
the past 12 months.
5.Treatment with any of the following monoclonal antibody therapies
within 120 days prior to Baseline: benralizumab, dupilumab,
mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.
6.Treatment with pramipexole (Mirapex®) within 30 days of Baseline.
7.Treatment with selected drugs known to have a substantial risk of
neutropenia in the past 30 days (see Appendix A).
8.Bronchial thermoplasty procedure in the past 12 months prior to SCR
Visit 1 or planned during the study period.
General medical history
9.Weight <40 kg at SCR Visit 2.
10.Current smoking within the past year, 12 months prior to SCR Visit 1
or a smoking history of >10 pack-years. Smoking includes tobacco,
vaping, and/or marijuana use.
11.Known or suspected alcohol or drug abuse
12.Uncontrolled severe hypertension: systolic blood pressure >180
mmHg or diastolic blood pressure >110 mmHg prior to the Baseline Visit
despite anti-hypertensive therapy.
13.History of malignancy that required surgery (excluding local and
wide-local excision), radiation therapy and/or systemic therapy during
the 5 years prior to Baseline Visit.
14.History of human immunodeficiency virus (HIV) infection or chronic
infection with hepatitis B or C.
15.A helminth parasitic infection diagnosed within 24 weeks prior to the
date informed consent, and assent when applicable, SCR Visit 1 that has
not been treated with or has failed to respond to standard of care
therapy.
16.Medical or other condition likely to interfere with participant's ability
to undergo study procedures, adhere to visit schedule, or comply with
study requirements.
17.Known or suspected noncompliance with medication.
18.Unwillingness or inability to follow the procedures outlined in the
protocol.
Clinical safety labs
19.Absolute neutrophil count <2.000x10ˆ9/L at SCR Visit 1 or SCR Visit
2.
20.Renal dysfunction, defined as an estimated glomerular filtration rate
(eGFR) <60 mL/min/1.73m2 at SCR Visit 2 (using the Chronic Kidney
Disease Epidemiology Collaboration [CKD-EPI] formula [Levey et al,
2009] for age ≥18 years at screening; using the Bedside Schwartz
[Schwartz and Work, 2009] eGFR formula for age <18).
21.Active liver disease defined as any known current infectious,
neoplastic, or metabolic pathology of the liver or unexplained elevations
in alanine aminotransferase (ALT), aspartate aminotransferase (AST),
>3x the upper limit of normal (ULN), or total bilirubin >2x ULN at SCR
visit 2 confirmed by a repeat abnormal measurement of the relevant
value(s), at least 1 week apart.
Cardiac safety
22.History of New York Heart Association class IV heart failure or last
known left ventricular ejection fraction <25%.
23.History of major adverse cardiovascular event (MACE) within 3
months prior to Baseline Visit.
24.History of cardiac arrhythmia within 3 months prior baseline visit that
is not controlled by medication or via ablation.
25.History of long QT syndrome.
26.Corrected QT interval by Fridericia (QTcF) interval >450 ms for males
and >470 ms for females at SCR Visit 2 or QTcF ≥480 ms for participants
with bundle branch block.
27.Clinically important abnormalities in resting ECG that may interfere
with the interpretation of QTcF interval changes at SCR Visit 2, including
resting heart rate <45 beats per minute (bpm) or >100 bpm.
Pregnancy/Lactation
28.Pregnant women or women breastfeeding.
29.Males who are unwilling to use an acceptable method of birth control
during the entire study period (ie, condom with spermicide). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Pre-bronchodilator (pre-BD) FEV1, absolute change from baseline, averaged over Weeks 20 and 24. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
•Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) averaged across visits at Weeks 20 and 24.
•Standardized version of the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12) change from baseline to Week 24.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please refer to the clinical study Protocol |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 17 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| 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 |
| Ukraine |
| Korea, Democratic People's Republic of |
| Taiwan |
| Canada |
| Israel |
| South Africa |
| United Kingdom |
| United States |
| Poland |
| Romania |
| Türkiye |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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