| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to Severe Persistent Asthma with Type 2 Inflammation |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| 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 assess the efficacy of CBP-201 versus placebo in patients with moderate to severe persistent asthma with type 2 inflammation as measured by lung function improvements
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| E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of CBP-201 on the incidence of asthma
exacerbations and time to first exacerbation
• To evaluate the effect of CBP-201 on the weekly average daily lung
function relative to placebo
• To evaluate the safety and tolerability of CBP-201
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|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adult male or female patient aged 18 to 75 years with a physician diagnosis of asthma for a minimum of 12 months, based on GINA 2020 Guidelines.
2. Patient is currently receiving treatment with medium to high dose ICS in combination with at least 1 additional reliever/controller for at least 90 days prior to the Screening Visit with a stable ICS dose at least 28 days prior to the Screening Visit.
3. Prebronchodilator (trough) FEV1 must be 40 to 85% of predicted normal at Screening and predose Baseline.
4. Patients must have ≥ 12% reversibility (and ≥ 200 mL difference) in FEV1 within 15 to 30 minutes after the administration of up to 4 puffs of albuterol/salbutamol at Screening. Note: Patients may repeat reversibility testing on a different day if the first attempt fails and justification is documented (eg, technical issues, reason to suspect that a longer bronchodilator washout is needed).
5. Blood eosinophil count ≥ 300 cells/μL at Screening. Note: Patients
consented on previous version of the protocol will not be considered
ineligible based on lower eosinophil counts at screening, or at baseline,
or in the medical history. Also, for patients on maintenance OCS
consented on previous version of the protocol will not be considered
ineligible regardless of eosinophil count.
Note: If patients' eosinophils are less than 300 cells/μL at Screening,
labs may be repeated once within 28-day Screening Period otherwise
they will be screen failed.
6. Six-question Asthma Control Questionnaire (ACQ) score ≥ 1.5 at Screening and Baseline.
7. Patient has experienced an asthma exacerbation at least once in the past 12 months, defined here as:
- Use of physician prescribed systemic corticosteroid [oral or parenteral], or
- Asthma requiring treatment increase of approximately 4 times the baseline dose of ICS, or
- Hospitalization or emergency medical care due to asthma.
Note: If patient is maintained on oral steroids, exacerbation requiring an increase in dose of at least 2-fold is considered adequate to fulfil this criterion. In the event the physician is uncertain that a patient meets the criteria of exacerbation defined within the protocol, the Medical Monitor(s) should be contacted for consultation.
8. Patient demonstrates acceptable inhaler, peak flow meter, and spirometry techniques during Screening Period, in the opinion of the Investigator.
9. Patient demonstrates at least 70% compliance with usual asthma controller use during Run-in Period, based on their patient diary in the 7 days prior to dosing.
10. Patient demonstrates at least 70% compliance with recording of
symptom scores in patient-reported outcomes (PRO) diary completion
during Run-in Period and in their hand-held pulmonary function device in
the 7 days prior to dosing.
11. Patient is able to understand and willing to sign the informed consent form (ICF).
12. Patient is willing and able to comply with clinic visit schedule and study-related procedures, in the opinion of the Investigator.
13. Male patients and their female partners agree to practice adequate and effective forms of contraception through the duration of the study from first dose to 8 weeks beyond the last dose of study drug (see Section 4.5.3).
14. Female patients of childbearing potential who are sexually active with a non-sterilized male partner agree to practice adequate and effective forms of contraception from first dose to 8 weeks after last dose of study drug (see Section 4.5.3).
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| E.4 | Principal exclusion criteria |
15. Patient has a current diagnosis of a respiratory disorder other than asthma or other disease associated with elevated peripheral eosinophil counts.
16. Patient has an acute upper or lower respiratory infection requiring antibiotics or antiviral
medication within 30 days prior to the date of informed consent or during the Screening/Run-in Period.
17. Patient experiences an asthma exacerbation at any time from 1 month prior to Screening up to and including the Baseline Visit. Exacerbation is defined as:
- Use of physician prescribed systemic corticosteroid, or
- Asthma requiring treatment increase of approximately 4 times the baseline dose of ICS, or
- Hospitalization or emergency medical care due to asthma.
18. Current smoker or former smoker with a smoking history of > 10 pack-years. Note: This includes tobacco, marijuana, and vaping products.
19. Patient is undergoing or planning to undergo any elective surgery during the study requiring general anesthesia.
20. Patient has received treatment with any marketed or investigational biologic drug for asthma or other diseases within 16 weeks or 5 half-lives prior to randomization, whichever is longer.
21. Patient has received treatment with any investigational nonbiologic drug within 30 days or 5 half-lives prior to randomization, whichever is longer.
22. Patient did not respond favorably to previous dupilumab treatment.
23. Patient has received specific immunotherapy within 3 months prior to randomization. Note: If the patient has received immunotherapy, a 3 -month washout period is required following the last dose of immunotherapy.
24. Patient is receiving medications or therapy that are prohibited as concomitant medications (See Section 4.5.1).
25. Patient has a known or suspected history of immunosuppression, including history of invasive opportunistic infections regardless of infection resolution; or unusually frequent, recurrent, or prolonged infections.
26. Patient has positive results at Screening for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody with positive HCV RNA polymerase chain reaction; or positive HIV serology at Screening.
27. Patient has a helminth parasitic infection diagnosed within 24 weeks prior to the date of informed consent that has not been treated with, or has failed to respond to, standard of care therapy.
28. Patient shows evidence of acute or chronic infection requiring treatment with antibacterials, antivirals, antifungals, antiparasitics, or antiprotozoals within 28 days of Screening, or significant viral infections within 28 days of Screening that may not have received antiviral treatment.
29. Patient receives live (attenuated) vaccinations within 7 days of Screening or plans to receive live (attenuated) vaccinations during the study.
30. Patient has any disorder that is not stable in the opinion of the Investigator and may affect the safety of the patient throughout the study; influence the findings of the studies or their interpretations; or impede the patient’s ability to complete the entire duration of study.
31. Patient has any clinically significant abnormal findings in physical examination, vital signs, or safety lab tests during Screening/Run-in Period; or any significant medical history which, in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient’s ability to complete entire duration of the study.
32. Patient is being treated with immunosuppressive therapy or biologic therapy for autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis).
33. Patient has a prolonged corrected QT (QTc) interval (male > 450 milliseconds, female > 470 milliseconds) or tachyarrhythmia.
34. Patient has any of the following laboratory abnormalities at Screening:
- Eosinophils > 1500 cells/mm3or 1.5*109/L
- Platelets < 100000 cells/mm3or 100*109/L
- Creatine phosphokinase (CPK) > 10 times the upper limit of normal (ULN)
- Alanine aminotransferase (ALT) > 2.5 times the ULN
- Aspartate aminotransferase (AST) ≥ 2.5 times the ULN
- Bilirubin > 2 times the ULN.
35. Patient has a history of alcohol or drug abuse within 12 months of Screening.
36. Patient has an allergy to L-histidine, trehalose, or Tween (polysorbate) 80 or a history of a systemic hypersensitivity reaction, other than localized injection site reaction, to any biologic drug.
37. Patient has a history of malignancy within 5 years prior to the Baseline Visit, with the following exceptions: patients with a history of completely treated carcinoma in situ of cervix and nonmetastatic squamous or basal cell carcinoma of the skin are allowed.
38. Female patient is pregnant, planning to become pregnant, or is breastfeeding. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is absolute change from Baseline in prebronchodilator (trough) FEV1 at Week 12.
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|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
•Absolute change from Baseline in prebronchodilator (trough) FEV1 at Weeks 1, 2, 4, 8 and 24
•Percent change from Baseline in prebronchodilator (trough) FEV1 at Weeks 1, 2, 4, 8, 12 and 24
•Change from Baseline in other lung function measurements [percentage predicted FEV1, morning and evening peak expiratory flow (PEF) and FEV1]
•Time to exacerbation and number of events during the 24-week Treatment Period and number of
events during the 24-week Treatment Period
•Proportion of patients with ≥ 1 asthma exacerbation during the 24-week Treatment Period
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| 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 |
| China |
| Korea, Republic of |
| United States |
| Poland |
| Hungary |
| Ukraine |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 1 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 8 |
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