A Study to Evaluate CBP-201, Rademikibart, in Adult Patients With Chronic Rhinosinusitis With Nasal Polyps

NCT ID: NCT04783389

Last Updated: 2023-10-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-16
• Study Completion Date: 2022-06-10

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.

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CBP-201 Dose 1

CBP-201 Dose 1 subcutaneous (SC) injection.

Group Type: EXPERIMENTAL

CBP-201

Intervention Type: DRUG

CBP-201 subcutaneous (SC) injection.

CBP-201 Dose 2

CBP-201 Dose 2 subcutaneous (SC) injection.

Group Type: EXPERIMENTAL

CBP-201

Intervention Type: DRUG

CBP-201 subcutaneous (SC) injection.

Placebo

Placebo subcutaneous (SC) injection.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo subcutaneous (SC) injection.

Interventions

CBP-201

CBP-201 subcutaneous (SC) injection.

Intervention Type: DRUG

Placebo

Placebo subcutaneous (SC) injection.

Intervention Type: DRUG

Other Intervention Names

rademikibart

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Connect Biopharm LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suzhou Connect

Role: STUDY_DIRECTOR

Connect Biopharm LLC

Locations

Connect Investigative Site 130

Birmingham, Alabama, United States

Connect Investigative Site 124

Bakersfield, California, United States

Connect Investigative Site 125

La Mesa, California, United States

Connect Investigative Site 134

Los Angeles, California, United States

Connect Investigative Site 128

Temecula, California, United States

Connect Investigative Site 119

Torrance, California, United States

Connect Investigative Site 114

Miami, Florida, United States

Connect Investigative Site 109

Miami, Florida, United States

Connect Investigative Site 116

Tampa, Florida, United States

Connect Investigative Site 111

Chicago, Illinois, United States

Connect Investigative Site 126

Chicago, Illinois, United States

Connect Investigative Site 132

Louisville, Kentucky, United States

Connect Investigative Site 110

White Marsh, Maryland, United States

Connect Investigative Site 121

Ann Arbor, Michigan, United States

Connect Investigative Site 127

St Louis, Missouri, United States

Connect Investigative Site 102

Princeton, New Jersey, United States

Connect Investigative Site 105

Rochester, New York, United States

Connect Investigative Site 113

The Bronx, New York, United States

Connect Investigative Site 117

Winston-Salem, North Carolina, United States

Connect Investigative Site 123

Cincinnati, Ohio, United States

Connect Investigative Site 133

Columbus, Ohio, United States

Connect Investigative Site 112

Tulsa, Oklahoma, United States

Connect Investigative Site 122

Tulsa, Oklahoma, United States

Connect Investigative Site 108

Charleston, South Carolina, United States

Connect Investigative Site 107

Memphis, Tennessee, United States

Connect Investigative Site 106

Austin, Texas, United States

Connect Investigative Site 104

Dallas, Texas, United States

Connect Investigative Site 120

Houston, Texas, United States

Connect Investigative Site 101

Sherman, Texas, United States

Connect Investigative Site 129

St. George, Utah, United States

Connect Investigative Site 118

Norfolk, Virginia, United States

Connect Investigative Site 115

Bellingham, Washington, United States

Connect Investigative Site 307

Bengbu, Anhui, China

Connect Investigative Site 303

Chongqing, Chongqing Municipality, China

Connect Investigative Site 302

Nanning, Guangxi, China

Connect Investigative Site 309

Jingzhou, Hubei, China

Connect Investigative Site 306

Nanjing, Jiangsu, China

Connect Investigative Site 308

Yangzhou, Jiangsu, China

Connect Investigative Site 313

Shenyang, Liaoning, China

Connect Investigative Site 304

Qingdao, Shandong, China

Connect Investigative Site 301

Shanghai, Shanghai Municipality, China

Connect Investigative Site 312

Shanghai, Shanghai Municipality, China

Connect Investigative Site 311

Taiyuan, Shanxi, China

Connect Investigative Site 305

Xi’an, Shanxi, China

Connect Investigative Site 310

Hangzhou, Zhejiang, China

Connect Investigative Site 401

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Connect Investigative Site 407

Krakow, Lesser Poland Voivodeship, Poland

Connect Investigative Site 402

Krakow, Lesser Poland Voivodeship, Poland

Connect Investigative Site 409

Lubin, Lower Silesian Voivodeship, Poland

Connect Investigative Site 408

Warsaw, Masovian Voivodeship, Poland

Connect Investigative Site 403

Warsaw, Masovian Voivodeship, Poland

Connect Investigative Site 405

Rzeszów, Podkarpackie Voivodeship, Poland

Connect Investigative Site 404

Bialystok, Podlaskie Voivodeship, Poland

Connect Investigative Site 406

Zabrze, Silesian Voivodeship, Poland

Connect Investigative Site 604

Barcelona, Catalonia, Spain

Connect Investigative Site 602

Córdoba, , Spain

Connect Investigative Site 601

Madrid, , Spain

Connect Investigative Site 603

Seville, , Spain

Connect Investigative Site 501

Dnipropetrovsk, Dnipro, Ukraine

Connect Investigative Site 507

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Connect Investigative Site 508

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Connect Investigative Site 510

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Connect Investigative Site 509

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Connect Investigative Site 506

Poltava, Poltava Oblast, Ukraine

Connect Investigative Site 504

Lutsk, Volyn Oblast, Ukraine

Connect Investigative Site 503

Kyiv, , Ukraine

Connect Investigative Site 502

Kyiv, , Ukraine

Connect Investigative Site 505

Kyiv, , Ukraine

Countries

United States; China; Poland; Spain; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CBP-201-WW003

Identifier Type: -

Identifier Source: org_study_id