A Study to Evaluate CBP-201, Rademikibart, in Adult Patients With Chronic Rhinosinusitis With Nasal Polyps
Condition: Chronic Rhinosinusitis With Nasal Polyps
MeSH terms: Sinusitis; Nasal Polyps; Polyps
Intervention: CBP-201; Placebo
Intervention description: CBP-201 subcutaneous (SC) injection.; Placebo subcutaneous (SC) injection.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This study will evaluate the effect of CBP-201, rademikibart, in adult patients with Chronic
      Rhinosinusitis with Nasal Polyps (CRSwNP).
    

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.