Clinical trial NCT04773678: Efficacy and Safety of CBP-201 in Patients With Moderate to Severe Persistent Asthma With Type 2 Inflammation
Official title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Efficacy and Safety Study of CBP-201 in Patients With Moderate to Severe Persistent Asthma With Type 2 Inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Moderate to Severe Persistent Asthma
Keywords: Type 2 inflammation
Lead sponsor: Connect Biopharm LLC
Sponsor class: INDUSTRY
First posted: 2021-02-26
Enrollment: 322
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety of two dose levels of CBP-201 in patients with moderate to severe persistent asthma with Type 2 inflammation.

Detailed description: This is a multicenter, randomized, double-blind, parallel group, placebo-controlled study to assess the efficacy and safety of two dose levels of CBP-201 administered to eligible patients with moderate to severe persistent asthma with Type 2 inflammation compared to placebo. CBP-201 is administered as a subcutaneous (SC) injection. The study is divided into a treatment period of 24 weeks and a follow-up period of 8 weeks.

Eligibility criteria: 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 the Global Initiative for Asthma (GINA) 2020 Guidelines.
2. Patient is currently receiving treatment with medium to high dose inhaled corticosteroids (ICS) in combination with at least 1 additional reliever/controller for at least 90 days prior to the Screening Visit with a stable dose of ICS at least 28 days prior to the Screening Visit.

   Note:
   * Patients receiving ICS equivalent to ≥ 226 μg fluticasone propionate twice daily or equipotent ICS daily dosage of a maximum of 2000 μg/day fluticasone propionate (or equivalent) in combination with a second reliever/controller (eg, long-acting ß agonist \[LABA\], leukotriene receptor antagonist \[LTRA\], long-acting muscarinic antagonist \[LAMA\], theophylline) are eligible.
   * Patients receiving fluticasone furoate/vilanterol with fluticasone furoate ≥ 200 μg once daily are eligible.
   * Patients receiving budesonide/formoterol with budesonide ≥ 640 μg/day are eligible.
   * Patients requiring a third reliever/controller for their asthma are eligible.
   * Patients requiring maintenance oral corticosteroids (OCS) with a stable dose ≤ 10 mg/day prednisone or equivalent OCS in addition to ICS are eligible; OCS total daily dose must have been stable at least 28 days prior to Screening.
3. Prebronchodilator (trough) forced expiratory volume in the first second of expiration (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.
5. Blood eosinophil count ≥ 300 cells/μL at Screening.
6. Asthma Control Questionnaire, 6-question (ACQ-6) 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.
8. Patient demonstrates acceptable inhaler, peak flow meter, and spirometry techniques during the 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 the patient-reported outcomes (PRO) diary completion during Run-in Period and in their handheld 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 of child-bearing potential agree to practice adequate and effective forms of contraception through the duration of the study from first dose to 8 weeks after the last dose of study drug.
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.

    Exclusion Criteria:

    -

    A patient who meets any of the following criteria will be ineligible to participate in this study:
15. Patient has a current diagnosis of a respiratory disorder other than asthma (eg, active lung infection, chronic obstructive pulmonary disease (COPD), bronchiectasis, pulmonary fibrosis, cystic fibrosis) or other disease associated with elevated peripheral eosinophil counts (eg, allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome).
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. Note: Patients must be symptom-free for at least 30 days.
17. Patient experiences ana asthma exacerbation at any time from 1 month prior to the Screening Visit up to and including the Baseline Visit. Exacerbation is defined 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.
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 (eg, omalizumab, benralizumab, mepolizumab, reslizumab, dupilumab) 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 (e.g. therapy failure or patient experienced an adverse reaction to 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.
25. Patient has a known or suspected history of immunosuppression, including history of invasive opportunistic infections, such as aspergillosis, coccidioidomycosis, histoplasmosis, HIV, listeriosis, pneumocystosis, pulmonary non-tuberculosis mycobacteria, or tuberculosis, regardless of infection resolution; or unusually frequent, recurrent, or prolonged infections. Note: Tuberculosis testing will be performed on a country-by-country basis according to local guidelines if required by regulatory authorities or ethics committees (ECs).
26. Patient has positive results at Screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HbsAqHBsAq), or hepatitis C antibody (HbsAqHBsAq) 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 (eg, influenza receiving only symptomatic 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, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment.
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/mmE3 or 1.5\*10E9/L
    * Platelets \< 100000 cells/mmE3 or 100\*10E9/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.

Primary outcomes:
measure: Absolute change in prebronchodilator (trough) forced expiratory volume in the first second of expiration (FEV1)
timeFrame: at Week 12
Secondary outcomes:
measure: Absolute change in prebronchodilator (trough) FEV1
timeFrame: at Weeks 1, 2, 4, 8 and 24
measure: Percent change in prebronchodilator (trough) FEV1
timeFrame: at Weeks 1, 2, 4, 8, 12 and 24
measure: Change in other lung function measurements
timeFrame: From Baseline to Week 24
measure: Time to severe exacerbation and number of events
timeFrame: From Baseline to Week 24
measure: Proportion of patients with ≥ 1 asthma exacerbation
timeFrame: From Baseline to Week 24
measure: Incidence, type and severity of Adverse Event (AE)
timeFrame: From Baseline to Week 32
measure: Pharmacokinetics (Steady-state trough PK profile)
timeFrame: From Baseline to Week 32
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Connect Investigative Site 154
state: Arizona
city: Huntington Beach
country: United States
facility: Connect Investigative Site 109
state: California
city: Huntington Beach
country: United States
facility: Connect Investigative Site 143
state: California
city: Lancaster
country: United States
facility: Connect Investigative Site 132
state: California
city: Mission Viejo
country: United States
facility: Connect Investigative Site 125
state: California
city: San Jose
country: United States
facility: Connect Investigative Site 103
state: California
city: Hialeah
country: United States
facility: Connect Investigative Site 161
state: Florida
city: Hollywood
country: United States
facility: Connect Investigative Site 114
state: Florida
city: Leesburg
country: United States
facility: Connect Investigative Site 142
state: Florida
city: Miami Gardens
country: United States
facility: Connect Investigative Site 165
state: Florida
city: Miami Lakes
country: United States
facility: Connect Investigative Site 110
state: Florida
city: Miami
country: United States
facility: Connect Investigative Site 104
state: Florida
city: Miami
country: United States
facility: Connect Investigative Site 166
state: Florida
city: Miami
country: United States
facility: Connect Investigative Site 118
state: Florida
city: Miami
country: United States
facility: Connect Investigative Site 162
state: Florida
city: Miami
country: United States
facility: Connect Investigative Site 163
state: Florida
city: Miami
country: United States
facility: Connect Investigative Site 164
state: Florida
city: Miami
country: United States
facility: Connect Investigative Site 105
state: Florida
city: Winter Park
country: United States
facility: Connect Investigative Site 123
state: Florida
city: Bangor
country: United States
facility: Connect Investigative Site 124
state: Maine
city: White Marsh
country: United States
facility: Connect Investigative Site 120
state: Maryland
city: West Bloomfield
country: United States
facility: Connect Investigative Site 146
state: Michigan
city: Saint Louis
country: United States
facility: Connect Investigative Site 112
state: Missouri
city: Bellevue
country: United States
facility: Connect Investigative Site 119
state: Nebraska
city: North Las Vegas
country: United States
facility: Connect Investigative Site 144
state: Nevada
city: Princeton
country: United States
facility: Connect Investigative Site 111
state: New Jersey
city: Buffalo
country: United States
facility: Connect Investigative Site 117
state: New York
city: New York
country: United States
facility: Connect Investigative Site 153
state: New York
city: Winston-Salem
country: United States
facility: Connect Investigative Site 122
state: North Carolina
city: Cincinnati
country: United States
facility: Connect Investigative Site 136
state: Ohio
city: Toledo
country: United States
facility: Connect Investigative Site 147
state: Ohio
city: Edmond
country: United States
facility: Connect Investigative Site 107
state: Oklahoma
city: Oklahoma City
country: United States
facility: Connect Investigative Site 149
state: Oklahoma
city: Warwick
country: United States
facility: Connect Investigative Site 129
state: Rhode Island
city: Austin
country: United States
facility: Connect Investigative Site 116
state: Texas
city: Boerne
country: United States
facility: Connect Investigative Site 102
state: Texas
city: Dallas
country: United States
facility: Connect Investigative Site 121
state: Texas
city: El Paso
country: United States
facility: Connect Investigative Site 108
state: Texas
city: Katy
country: United States
facility: Connect Investigative Site 150
state: Texas
city: Bengbu
country: China
facility: Connect Investigative Site 206
state: Anhui
city: Beijing
country: China
facility: Connect Investigative Site 201
state: Beijing
city: Beijing
country: China
facility: Connect Investigative Site 216
state: Beijing
city: Beijing
country: China
facility: Connect Investigative Site 209
state: Beijing
city: Beijing
country: China
facility: Connect Investigative Site 215
state: Beijing
city: Guangzhou
country: China
facility: Connect Investigative Site 203
state: Guangdong
city: Luoyang
country: China
facility: Connect Investigative Site 211
state: Henan
city: Wuhan
country: China
facility: Connect Investigative Site 213
state: Hubei
city: Changsha
country: China
facility: Connect Investigative Site 202
state: Hunan
city: Baotou
country: China
facility: Connect Investigative Site 204
state: Inner Mongolia
city: Baotou
country: China
facility: Connect Investigative Site 214
state: Inner Mongolia
city: Hohhot
country: China
facility: Connect Investigative Site 210
state: Inner Mongolia
city: Wuxi
country: China
facility: Connect Investigative Site 205
state: Jiangsu
city: Yangzhou
country: China
facility: Connect Investigative Site 208
state: Jiangsu
city: Changchun
country: China
facility: Connect Investigative Site 212
state: Jilin
city: Shenyang
country: China
facility: Connect Investigative Site 220
state: Liaoning
city: Shanghai
country: China
facility: Connect Investigative Site 207
state: Shanghai
city: Shanghai
country: China
facility: Connect Investigative Site 218
state: Shanghai
city: Taiyuan
country: China
facility: Connect Investigative Site 221
state: Shanxi
city: Taiyuan
country: China
facility: Connect Investigative Site 222
state: Shanxi
city: Ürümqi
country: China
facility: Connect Investigative Site 224
state: Xinjiang
city: Ningbo
country: China
facility: Connect Investigative Site 217
state: Zhejiang
city: Püspökladány
country: Hungary
facility: Connect Investigative Site 304
state: Hajdú-Bihar
city: Szombathely
country: Hungary
facility: Connect Investigative Site 303
state: Vas
city: Incheon
country: Korea, Republic of
facility: Connect Investigative Site 505
state: Gyeonggi
city: Seongnam-si
country: Korea, Republic of
facility: Connect Investigative Site 503
state: Gyeonggi
city: Seoul
country: Korea, Republic of
facility: Connect Investigative Site 501
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Connect Investigative Site 502
state: Seoul Teugbyeolsi
city: Lubin
country: Poland
facility: Connect Investigative Site 403
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Connect Investigative Site 408
state: Dolnoslaskie
city: Skierniewice
country: Poland
facility: Connect Investigative Site 406
state: Lódzkie
city: Kraków
country: Poland
facility: Connect Investigative Site 402
state: Malopolskie
city: Kraków
country: Poland
facility: Connect Investigative Site 401
state: Malopolskie
city: Białystok
country: Poland
facility: Connect Investigative Site 404
state: Podlaskie
city: Białystok
country: Poland
facility: Connect Investigative Site 405
state: Podlaskie
city: Częstochowa
country: Poland
facility: Connect Investigative Site 410
state: Świętokrzyskie
city: Skarżysko-Kamienna
country: Poland
facility: Connect Investigative Site 407
state: Świętokrzyskie
Study officials:
affiliation: Connect Biopharm LLC
name: Suzhou Connect
role: STUDY_DIRECTOR
References: