Clinical trial NCT04783389: A Study to Evaluate CBP-201, Rademikibart, in Adult Patients With Chronic Rhinosinusitis With Nasal Polyps
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate CBP-201 in Adult Patients With Chronic Rhinosinusitis With Nasal Polyps
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Lead sponsor: Connect Biopharm LLC
Sponsor class: INDUSTRY
First posted: 2021-03-05
Enrollment: 40
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 effect of CBP-201, rademikibart, in adult patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP).

Detailed description: This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the effect of CBP-201 on a background of mometasone furoate nasal spray (MFNS) in reducing endoscopic nasal polyp score (NPS) and nasal congestion/obstruction score (NCS) severity in eligible patients with CRSwNP whose disease remains inadequately controlled despite daily treatment with intranasal corticosteroid (INCS) therapy in comparison 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. Female and male patients aged ≥ 18 and ≤ 75 years at the time of screening.
2. Patients who are diagnosed with chronic rhinosinusitis with bilateral polyps despite treatment with systemic corticosteroid within the past 2 years and/or medical contraindication/intolerance to systemic corticosteroids. The polyps have a minimum bilateral nasal polyps score (NPS) of 5 out of a maximum score of 8 with at least a score of 2 for each nostril at screening and baseline evaluated by endoscopy.
3. Nasal congestion/blockade/obstruction with moderate or severe symptom severity (Nasal Congestion Score of \> 2) at screening and a weekly average severity of \> 1 at time of randomization.
4. Patients using a documented stable dose of nasal mometasone at least 200 mcg/day, or an equivalent daily dose of another inhaled nasal corticosteroid (INCS), for at least 28 days before randomization and willing to continue the dose for the duration of the study. Note: For patients who are using an alternative INCS product other than mometasone furoate nasal spray (MFNS) prior to the screening visit, the investigator must switch the patient to MFNS at V1.
5. Patients willing to enter Patient Diary daily symptom assessments and maintain stable dosing with MFNS with a compliance of at least 70% in the 7 days preceding randomization. Note: Patients must use nasal mometasone at least 200 mcg/day, or equivalent, for at least 28 days before randomization, which can include days prior to screening with supportive documentation. Run-in can be 7-31 days with the compliance determined in the week prior to dosing.
6. Male patients who are non-sterilized and sexually active with a female partner of childbearing potential agree to use highly effective contraception from randomization until 8 weeks after last dose.
7. Female patients of childbearing potential who are sexually active with a nonsterilized male partner should have a confirmed negative serum beta-human chorionic gonadotropin test at Visit 1 and agrees to use highly effective contraception from signing of informed consent throughout the duration of the study and for 8 weeks after last dose.
8. Patient is able to understand and willing to sign the informed consent form (ICF) prior to any study related procedures being performed.
9. Willing and able to comply with all study visits and study-related procedures, in the opinion of the Investigator.

   Exclusion Criteria:

   -

   A patient who meets any of the following criteria will be ineligible to participate in this study:
10. Patients unable to use MFNS.
11. Patients who are taking or have taken the following prohibited therapies as specified:

    1. Systemic steroids within 28 days prior to screening,
    2. Other nonbiologic investigational drugs within 60 days (or 5 half-lives, whichever is longer) of screening,
    3. Intranasal corticosteroid drops or corticosteroid-administering devices (eg, OptiNose device or stents) within 28 days prior to screening,
    4. Non-steroidal immunosuppressants (eg, cyclosporine, methotrexate, azathioprine, mycophenolate, sirolimus, tacrolimus) within 60 days or 5 half-lives, whichever is longer, of screening,
    5. Any monoclonal antibody therapy (eg, benralizumab, mepolizumab, omalizumab, reslizumab, dupilumab) or investigational biologic drug for asthma or other diseases within 60 days or 5 half-lives, whichever is longer, of screening,
    6. Leukotriene antagonists/modifiers within 7 days prior to screening for patients who were not on continuous treatment for ≥ 30 days prior to screening,
    7. Allergen immunotherapy for patients who were not on maintenance treatment for at least 90 days prior to screening
12. Patients who did not respond favorably to previous dupilumab treatment (eg, therapy failure or patient experienced an adverse reaction to treatment).
13. Patients who have undergone any nasal surgery (including polypectomy) within 6 months before screening; or have a history of sinus or nasal surgery modifying the structure of the nose such that assessment of NPS is not possible, or have had uncontrolled epistaxis requiring surgical or procedural intervention, including nasal packing.
14. Patients with conditions/concomitant diseases making them non evaluable at screening or for the primary efficacy endpoint such as: antrochoanal polyps, nasal septal deviation that would occlude at least 1 nostril, acute sinusitis, nasal infection or upper respiratory infection at screening or within 2 weeks before screening, ongoing rhinitis medicamentosa; known or suspected diagnosis of cystic fibrosis; chronic granulomatous disease and granulomatous vasculitis, granulomatosis with polyangiitis (Wegener's Granulomatosis), eosinophilic granulomatous with polyangiitis (Churg-Strauss syndrome), Young's syndrome, primary dyskinetic ciliary syndromes (eg, Kartagener's syndrome) or other dyskinetic ciliary syndromes.
15. Signs or a CT scan suggestive of Allergic Fungal Rhinosinusitis.
16. Patients with co-morbid asthma are excluded if:

    1. Forced Expiratory Volume in 1 second (FEV1) ≤ 50% of normal predicted value OR
    2. An exacerbation within 90 days prior screening that required hospitalization (\> 24 hours) OR
    3. Are on a daily dose of inhaled corticosteroids (ICS) higher than 1000 mcg fluticasone or the equivalent.
17. Known or suspected history of immunosuppression, including history of invasive opportunistic infections, such as aspergillosis, coccidioidomycosis, histoplasmosis, human immunodeficiency virus (HIV), listeriosis, pneumocystosis, or tuberculosis, despite infection resolution; or unusually frequent, recurrent or prolonged infections. Tuberculosis testing would be performed on a country-by-country basis according to local guidelines if required by regulatory authorities or ethics committees.
18. Patients who have active Hepatitis B, Hepatitis C or HIV infections as determined by positive results at Screening for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb); or hepatitis C (HCV) antibody; or positive HIV serology. Note: Patients who test positive for HBvAb, negative for HBsAg and subsequently confirmed positive for HBsAb, indicating resolved natural infection (confirmed by negative HBV-DNA), may participate. Patients with positive HCV may participate if subsequent viral load is confirmed negative.
19. A helminth parasitic infection diagnosed within 24 weeks prior to the date of informed consent that has not been treated, or has failed to respond to, standard of care therapy.
20. Evidence of infection requiring treatment with systemic antibacterials, antivirals, antifungals, antiparasitics, or antiprotozoals within 7 days before baseline, or viral infections within 14 days before screening that may not have received antiviral treatment.
21. Live, attenuated vaccinations within 28 days prior to screening or planned live, attenuated vaccinations during the study.
22. Pregnant or intent to become pregnant during the study, or breast-feeding women.
23. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and may affect the safety of the patient throughout the study, or influence the findings of the studies or their interpretations, or impede the patient's ability to complete the entire duration of study.
24. Any clinically significant abnormal findings in physical examination, vital signs, safety lab tests during screening/run-in period, which in the opinion of the investigator, may put the patient at risk because of their participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study.
25. Have any of the following laboratory abnormalities at Screening:

    1. Eosinophils \>1500 cells/mm3 (or 1.5 x 10E9/L)
    2. Platelets \<100000 cells/mm3 (or 100 x 10E9/L)
    3. Creatine phosphokinase (CPK) \> 10 upper limit of normal (ULN)
    4. Alanine aminotransferase (ALT) \> 2.5 times the ULN
    5. Aspartate aminotransferase (AST) ≥ 2.5 times the ULN
    6. Bilirubin ≥ 2 times the ULN
26. History of alcohol or drug abuse within 12 months prior to the date informed consent.
27. 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.
28. Plans to undergo any surgical procedure requiring general anesthesia during the study.
29. History of cancer: Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent. Note: Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date of informed consent.

Primary outcomes:
measure: Change in Endoscopic Nasal Polyp Score (NPS)
timeFrame: From Baseline to Week 24
measure: Change in Average Daily Nasal Congestion Score (NCS)
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Change in Percentage of Maxillary Sinus Volume Occupied by Disease
timeFrame: From Baseline to Week 24
measure: Change in University of Pennsylvania Smell Identification Test (UPSIT)
timeFrame: From Baseline to Week 24
measure: Change in Visual Analogue Scale for Rhinosinusitis (VAS-RS)
timeFrame: From Baseline to Week 24
measure: Change in Total Nasal Symptom Score (TNSS)
timeFrame: From Baseline to Week 24
measure: Change in 22-item Sinonasal Outcome Test (SNOT-22)
timeFrame: From Baseline to Week 24
measure: Change in Average Daily Anterior Rhinorrhea Score
timeFrame: From Baseline to Week 24
measure: Change in Average Daily Posterior Rhinorrhea Score
timeFrame: From Baseline to Week 24
measure: Change in Average Daily Loss of Smell Score
timeFrame: From Baseline to Week 24
measure: Change in Daily Subject-assessed Nasal Peak Inspiratory Flow (NPIF)
timeFrame: From Baseline to Week 24
measure: Change From Baseline in Blood Level of IgE
timeFrame: From Baseline to Week 32
measure: Change From Baseline in Peripheral Eosinophil Counts
timeFrame: From Baseline to Week 32
measure: Change From Baseline in Eosinophil Cationic Protein (ECP)
timeFrame: From Baseline to Week 32
measure: Change From Baseline in Thymus and Activation-regulated Chemokine (TARC)
timeFrame: From Baseline to Week 32
measure: Change From Baseline in Eotaxin-3
timeFrame: From Baseline to Week 32
measure: Change From Baseline in Periostin
timeFrame: From Baseline to Week 32
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Connect Investigative Site 130
state: Alabama
city: Bakersfield
country: United States
facility: Connect Investigative Site 124
state: California
city: La Mesa
country: United States
facility: Connect Investigative Site 125
state: California
city: Los Angeles
country: United States
facility: Connect Investigative Site 134
state: California
city: Temecula
country: United States
facility: Connect Investigative Site 128
state: California
city: Torrance
country: United States
facility: Connect Investigative Site 119
state: California
city: Miami
country: United States
facility: Connect Investigative Site 114
state: Florida
city: Miami
country: United States
facility: Connect Investigative Site 109
state: Florida
city: Tampa
country: United States
facility: Connect Investigative Site 116
state: Florida
city: Chicago
country: United States
facility: Connect Investigative Site 111
state: Illinois
city: Chicago
country: United States
facility: Connect Investigative Site 126
state: Illinois
city: Louisville
country: United States
facility: Connect Investigative Site 132
state: Kentucky
city: White Marsh
country: United States
facility: Connect Investigative Site 110
state: Maryland
city: Ann Arbor
country: United States
facility: Connect Investigative Site 121
state: Michigan
city: Saint Louis
country: United States
facility: Connect Investigative Site 127
state: Missouri
city: Princeton
country: United States
facility: Connect Investigative Site 102
state: New Jersey
city: Bronx
country: United States
facility: Connect Investigative Site 113
state: New York
city: Rochester
country: United States
facility: Connect Investigative Site 105
state: New York
city: Winston-Salem
country: United States
facility: Connect Investigative Site 117
state: North Carolina
city: Cincinnati
country: United States
facility: Connect Investigative Site 123
state: Ohio
city: Columbus
country: United States
facility: Connect Investigative Site 133
state: Ohio
city: Tulsa
country: United States
facility: Connect Investigative Site 112
state: Oklahoma
city: Tulsa
country: United States
facility: Connect Investigative Site 122
state: Oklahoma
city: Charleston
country: United States
facility: Connect Investigative Site 108
state: South Carolina
city: Memphis
country: United States
facility: Connect Investigative Site 107
state: Tennessee
city: Austin
country: United States
facility: Connect Investigative Site 106
state: Texas
city: Dallas
country: United States
facility: Connect Investigative Site 104
state: Texas
city: Houston
country: United States
facility: Connect Investigative Site 120
state: Texas
city: Sherman
country: United States
facility: Connect Investigative Site 101
state: Texas
city: Saint George
country: United States
facility: Connect Investigative Site 129
state: Utah
city: Norfolk
country: United States
facility: Connect Investigative Site 118
state: Virginia
city: Bellingham
country: United States
facility: Connect Investigative Site 115
state: Washington
city: Bengbu
country: China
facility: Connect Investigative Site 307
state: Anhui
city: Chongqing
country: China
facility: Connect Investigative Site 303
state: Chongqing
city: Nanning
country: China
facility: Connect Investigative Site 302
state: Guangxi
city: Jingzhou
country: China
facility: Connect Investigative Site 309
state: Hubei
city: Nanjing
country: China
facility: Connect Investigative Site 306
state: Jiangsu
city: Yangzhou
country: China
facility: Connect Investigative Site 308
state: Jiangsu
city: Shenyang
country: China
facility: Connect Investigative Site 313
state: Liaoning
city: Qingdao
country: China
facility: Connect Investigative Site 304
state: Shandong
city: Shanghai
country: China
facility: Connect Investigative Site 301
state: Shanghai
city: Shanghai
country: China
facility: Connect Investigative Site 312
state: Shanghai
city: Taiyuan
country: China
facility: Connect Investigative Site 311
state: Shanxi
city: Xi'an
country: China
facility: Connect Investigative Site 305
state: Shanxi
city: Hangzhou
country: China
facility: Connect Investigative Site 310
state: Zhejiang
city: Lubin
country: Poland
facility: Connect Investigative Site 409
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Connect Investigative Site 401
state: Kujawsko-Pomorskie
city: Kraków
country: Poland
facility: Connect Investigative Site 407
state: Malopolskie
city: Kraków
country: Poland
facility: Connect Investigative Site 402
state: Malopolskie
city: Warszawa
country: Poland
facility: Connect Investigative Site 403
state: Masovian
city: Warszawa
country: Poland
facility: Connect Investigative Site 408
state: Mazowieckie
city: Rzeszow
country: Poland
facility: Connect Investigative Site 405
state: Podkarpackie
city: Białystok
country: Poland
facility: Connect Investigative Site 404
state: Podlaskie
city: Zabrze
country: Poland
facility: Connect Investigative Site 406
state: Slaskie
city: Barcelona
country: Spain
facility: Connect Investigative Site 604
state: Catalunya
city: Córdoba
country: Spain
facility: Connect Investigative Site 602
city: Madrid
country: Spain
facility: Connect Investigative Site 601
city: Sevilla
country: Spain
facility: Connect Investigative Site 603
city: Dnipropetrovsk
country: Ukraine
facility: Connect Investigative Site 501
state: Dnipro
city: Ivano-Frankivs'k
country: Ukraine
facility: Connect Investigative Site 507
state: Ivano-Frankivs'ka Oblast'
city: Ivano-Frankivs'k
country: Ukraine
facility: Connect Investigative Site 508
state: Ivano-Frankivs'ka Oblast'
city: Ivano-Frankivs'k
country: Ukraine
facility: Connect Investigative Site 510
state: Ivano-Frankivs'ka Oblast'
city: Kharkiv
country: Ukraine
facility: Connect Investigative Site 509
state: Kharkivska Oblast
city: Poltava
country: Ukraine
facility: Connect Investigative Site 506
state: Poltavska Oblast
city: Lutsk
country: Ukraine
facility: Connect Investigative Site 504
state: Volyns'ka Oblast'
city: Kyiv
country: Ukraine
facility: Connect Investigative Site 503
city: Kyiv
country: Ukraine
facility: Connect Investigative Site 502
city: Kyiv
country: Ukraine
facility: Connect Investigative Site 505
Study officials:
affiliation: Connect Biopharm LLC
name: Suzhou Connect
role: STUDY_DIRECTOR
References: