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

NCT04783389 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CBP-201-WW003
• Study Type: interventional
• Target: 40
• Locations: 5 countries
• Sites: 68

Brief Summary

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

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Outcome Measures

Primary Outcomes (2)

• Change in Endoscopic Nasal Polyp Score (NPS)

  Change from baseline at Week 24 in endoscopic Nasal Polyp Score (NPS). Endoscopic NPS is assessed by central clinical specialist assessment of video recordings of nasal endoscopy. NPS is graded based on polyp size (recorded as the sum of the right and left nostril scores with a range of 0 to 8; higher scores indicate worse status). The scoring for each nostril is as follows: 0 No polyps, 1 Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate, 2 Polyps reaching below the lower border of the middle turbinate, 3 Large polyps reaching the lower border of the inferior turbinate or large polyps medial to the middle turbinate (i.e., reaching below the middle turbinate), 4 Large polyps causing complete obstruction of the inferior nasal cavity (i.e., touching the floor of the nose). The most improvement improvement possible from baseline would be -8 and the max worsening possible is +8.

  From Baseline to Week 24

• Change in Average Daily Nasal Congestion Score (NCS)

  Change from baseline at Week 24 in average daily Nasal Congestion Score (NCS). Daily NCS wase assessed by patient diary from screening and throughout the study by using a 0 to 3 categorical scale for severity of symptoms from none to severe over the past 24 hours. The patient diary prompt: "How would you rate nasal congestion over the last 24 hours?" The answers are: 0 None,1 Minor, 2 Moderate, 3 Severe. The lowest possible weekly average is 0 and the highest possible is 3. The higher the NCS score, the worse the symptoms. Change from baseline in weekly average score is the outcome. Maximal improvement in NCS would be -3 and maximal worsening would be +3.

  From Baseline to Week 24

Secondary Outcomes (15)

• Change in Percentage of Maxillary Sinus Volume Occupied by Disease

  From Baseline to Week 24

• Change in University of Pennsylvania Smell Identification Test (UPSIT)

  From Baseline to Week 24

• Change in Visual Analogue Scale for Rhinosinusitis (VAS-RS)

  From Baseline to Week 24

• Change in Total Nasal Symptom Score (TNSS)

  From Baseline to Week 24

• Change in 22-item Sinonasal Outcome Test (SNOT-22)

  From Baseline to Week 24

Study Arms (3)

CBP-201 Dose 1

EXPERIMENTAL

CBP-201 Dose 1 subcutaneous (SC) injection.

Drug: CBP-201

CBP-201 Dose 2

EXPERIMENTAL

CBP-201 Dose 2 subcutaneous (SC) injection.

Drug: CBP-201

Placebo

PLACEBO COMPARATOR

Placebo subcutaneous (SC) injection.

Drug: Placebo

Interventions

CBP-201 DRUG

CBP-201 subcutaneous (SC) injection.

Also known as: rademikibart

CBP-201 Dose 1; CBP-201 Dose 2

Placebo DRUG

Placebo subcutaneous (SC) injection.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and male patients aged ≥ 18 and ≤ 75 years at the time of screening.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Patient is able to understand and willing to sign the informed consent form (ICF) prior to any study related procedures being performed.
• Willing and able to comply with all study visits and study-related procedures, in the opinion of the Investigator.

You may not qualify if:

• A patient who meets any of the following criteria will be ineligible to participate in this study:
• Patients unable to use MFNS.
• Patients who are taking or have taken the following prohibited therapies as specified:
• Systemic steroids within 28 days prior to screening,
• Other nonbiologic investigational drugs within 60 days (or 5 half-lives, whichever is longer) of screening,
• Intranasal corticosteroid drops or corticosteroid-administering devices (eg, OptiNose device or stents) within 28 days prior to screening,
• Non-steroidal immunosuppressants (eg, cyclosporine, methotrexate, azathioprine, mycophenolate, sirolimus, tacrolimus) within 60 days or 5 half-lives, whichever is longer, of screening,
• 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,
• Leukotriene antagonists/modifiers within 7 days prior to screening for patients who were not on continuous treatment for ≥ 30 days prior to screening,
• Allergen immunotherapy for patients who were not on maintenance treatment for at least 90 days prior to screening
• Patients who did not respond favorably to previous dupilumab treatment (eg, therapy failure or patient experienced an adverse reaction to treatment).
• 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.
• 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.
• Signs or a CT scan suggestive of Allergic Fungal Rhinosinusitis.
• Patients with co-morbid asthma are excluded if:

Sponsors & Collaborators

• Connect Biopharm LLC: lead

Study Sites (68)

Connect Investigative Site 130

Birmingham, Alabama, 35205, United States

Location

Connect Investigative Site 124

Bakersfield, California, 93301, United States

Location

Connect Investigative Site 125

La Mesa, California, 91942, United States

Location

Connect Investigative Site 134

Los Angeles, California, 90048, United States

Location

Connect Investigative Site 128

Temecula, California, 92592, United States

Location

Connect Investigative Site 119

Torrance, California, 90503, United States

Location

Connect Investigative Site 114

Miami, Florida, 33135, United States

Location

Connect Investigative Site 109

Miami, Florida, 33155, United States

Location

Connect Investigative Site 116

Tampa, Florida, 33613, United States

Location

Connect Investigative Site 111

Chicago, Illinois, 60637, United States

Location

Connect Investigative Site 126

Chicago, Illinois, 60657, United States

Location

Connect Investigative Site 132

Louisville, Kentucky, 40205, United States

Location

Connect Investigative Site 110

White Marsh, Maryland, 21162, United States

Location

Connect Investigative Site 121

Ann Arbor, Michigan, 48109-0360, United States

Location

Connect Investigative Site 127

St Louis, Missouri, 63141, United States

Location

Connect Investigative Site 102

Princeton, New Jersey, 08540, United States

Location

Connect Investigative Site 105

Rochester, New York, 14618, United States

Location

Connect Investigative Site 113

The Bronx, New York, 10461, United States

Location

Connect Investigative Site 117

Winston-Salem, North Carolina, 27103, United States

Location

Connect Investigative Site 123

Cincinnati, Ohio, 45229, United States

Location

Connect Investigative Site 133

Columbus, Ohio, 43235, United States

Location

Connect Investigative Site 112

Tulsa, Oklahoma, 74136, United States

Location

Connect Investigative Site 122

Tulsa, Oklahoma, 74137, United States

Location

Connect Investigative Site 108

Charleston, South Carolina, 29425, United States

Location

Connect Investigative Site 107

Memphis, Tennessee, 38119, United States

Location

Connect Investigative Site 106

Austin, Texas, 75759, United States

Location

Connect Investigative Site 104

Dallas, Texas, 75231, United States

Location

Connect Investigative Site 120

Houston, Texas, 77074, United States

Location

Connect Investigative Site 101

Sherman, Texas, 75092, United States

Location

Connect Investigative Site 129

St. George, Utah, 84790, United States

Location

Connect Investigative Site 118

Norfolk, Virginia, 23507, United States

Location

Connect Investigative Site 115

Bellingham, Washington, 98225, United States

Location

Connect Investigative Site 307

Bengbu, Anhui, 233060, China

Location

Connect Investigative Site 303

Chongqing, Chongqing Municipality, 400042, China

Location

Connect Investigative Site 302

Nanning, Guangxi, 530021, China

Location

Connect Investigative Site 309

Jingzhou, Hubei, 434020, China

Location

Connect Investigative Site 306

Nanjing, Jiangsu, 210029, China

Location

Connect Investigative Site 308

Yangzhou, Jiangsu, 225007, China

Location

Connect Investigative Site 313

Shenyang, Liaoning, 110004, China

Location

Connect Investigative Site 304

Qingdao, Shandong, 266033, China

Location

Connect Investigative Site 301

Shanghai, Shanghai Municipality, 200031, China

Location

Connect Investigative Site 312

Shanghai, Shanghai Municipality, 201620, China

Location

Connect Investigative Site 311

Taiyuan, Shanxi, 30001, China

Location

Connect Investigative Site 305

Xi’an, Shanxi, 710061, China

Location

Connect Investigative Site 310

Hangzhou, Zhejiang, 310014, China

Location

Connect Investigative Site 401

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-605, Poland

Location

Connect Investigative Site 407

Krakow, Lesser Poland Voivodeship, 30-033, Poland

Location

Connect Investigative Site 402

Krakow, Lesser Poland Voivodeship, 31-411, Poland

Location

Connect Investigative Site 409

Lubin, Lower Silesian Voivodeship, 59-300, Poland

Location

Connect Investigative Site 408

Warsaw, Masovian Voivodeship, 00-892, Poland

Location

Connect Investigative Site 403

Warsaw, Masovian Voivodeship, 02-793, Poland

Location

Connect Investigative Site 405

Rzeszów, Podkarpackie Voivodeship, 35-055, Poland

Location

Connect Investigative Site 404

Bialystok, Podlaskie Voivodeship, 15-879, Poland

Location

Connect Investigative Site 406

Zabrze, Silesian Voivodeship, 41-800, Poland

Location

Connect Investigative Site 604

Barcelona, Catalonia, 08208, Spain

Location

Connect Investigative Site 602

Córdoba, Spain

Location

Connect Investigative Site 601

Madrid, 28040, Spain

Location

Connect Investigative Site 603

Seville, 41009, Spain

Location

Connect Investigative Site 501

Dnipropetrovsk, Dnipro, 49006, Ukraine

Location

Connect Investigative Site 507

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76000, Ukraine

Location

Connect Investigative Site 508

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76000, Ukraine

Location

Connect Investigative Site 510

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76000, Ukraine

Location

Connect Investigative Site 509

Kharkiv, Kharkivs’ka Oblast’, 61124, Ukraine

Location

Connect Investigative Site 506

Poltava, Poltava Oblast, 36038, Ukraine

Location

Connect Investigative Site 504

Lutsk, Volyn Oblast, 43005, Ukraine

Location

Connect Investigative Site 503

Kyiv, 2002, Ukraine

Location

Connect Investigative Site 502

Kyiv, 3049, Ukraine

Location

Connect Investigative Site 505

Kyiv, 3057, Ukraine

Location

Limitations and Caveats

The study was prematurely discontinued after 40 patients were enrolled due to recruitment issues resulting from the COVID-19 pandemic and operational issues such as the inability to fully conduct/implement the study (e.g., monitoring, logistics of drug supply, transportation of clinical testing samples, etc.) due to the Russian invasion of Ukraine in Mar 2022. Because only limited data was collected, no definitive conclusions can be made at the pre-planned 24-week primary endpoint.

Results Point of Contact

• Title: Dr. Malinda Longphre, PhD, Head of Clinical Operations
• Organization: Connect Biopharma

mlongphre@connectpharm.com

+1 510 520 3361

Study Officials

• Suzhou Connect

  Connect Biopharm LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 5, 2021
• Study Start: June 16, 2021
• Primary Completion: April 15, 2022
• Study Completion: June 10, 2022
• Last Updated: October 17, 2023
• Results First Posted: October 17, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); CN (13); UA (10); US (32); PL (9)