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Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID) (ORCHID)

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ClinicalTrials.gov Identifier: NCT04157335
Recruitment Status : Recruiting
First Posted : November 8, 2019
Last Update Posted : March 25, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a randomized, double-blind, placebo-controlled, parallel-group, international, multicenter, Phase 3 study to evaluate the efficacy and safety of repeat dosing of benralizumab 30 mg administered subcutaneously (SC) versus placebo in patients with severe nasal polyposis.

Condition or disease Intervention/treatment Phase
Nasal Polyposis Biological: Benralizumab 30 mg Biological: Matched placebo Phase 3

Detailed Description:
Approximately 148 patients will be randomized to receive benralizumab 30 mg SC or matching placebo. After enrolment, eligible patients will enter a 5-week screening/run in period. Patients who meet eligibility criteria will be randomised 1:1 at Week 0 (Day 0) to receive either placebo or benralizumab 30 mg SC every 4 weeks for the first 3 doses (Weeks 0, 4 and 8) and every 8 weeks thereafter (Weeks 16, 24, 32, 40 and 48). An end of treatment visit will be conducted at Week 56.The first up to 74 patients that complete the 56-week treatment will have a 24-week follow-up (FU) period without dosing to assess durability of benefit. These patients will have the FU for the final safety assessment at week 80. The remaining patients will have a last FU visit 12 weeks after last dose for final safety assessments at week 60.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 148 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multicentre, Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Benralizumab in Patients With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID)
Actual Study Start Date : November 25, 2019
Estimated Primary Completion Date : July 12, 2022
Estimated Study Completion Date : July 12, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Benralizumab
Benralizumab administered subcutaneously
Biological: Benralizumab 30 mg

Benralizumab is 30 mg/ml solution for injection in accessorized pre-filled syringe, 1 ml fill volume.

Benralizumab 30 mg subcutaneously will be injected every 4 weeks for the first 3 doses (Weeks 0, 4 and 8) and every 8 weeks thereafter (Weeks 16, 24, 32, 40 and 48).


Placebo Comparator: Placebo
Placebo administered subcutaneously
Biological: Matched placebo

Matching placebo solution for injection in accessorized pre-filled syringe. 1 ml fill volume.

Matching placebo subcutaneously will be injected every 4 weeks for the first 3 doses (Weeks 0, 4 and 8) and every 8 weeks thereafter (Weeks 16, 24, 32, 40 and 48).





Primary Outcome Measures :
  1. Endoscopic total nasal polyp score [ Time Frame: Baseline and Week 56 ]
    Change in endoscopic total nasal polyp score (nasal polyp score range from 0 to 8, higher scores mean a worse outcome)

  2. Nasal blockage score [ Time Frame: Baseline and week 56 ]
    Change in mean nasal blockage score (The severity of nasal blockage can be rated as 0 - None; 1 - Mild; 2 - Moderate; 3 - Severe )


Secondary Outcome Measures :
  1. Lund Mackay Score [ Time Frame: Baseline and week 56 ]
    Change in Lund Mackay Score (Lund Mackay Score range from 0 to 24, higher scores mean a worse outcome)

  2. Nasal polyp surgery [ Time Frame: By week 56 ]
    Time to first nasal polyp surgery

  3. Patients with surgery for nasal polyp [ Time Frame: By week 56 ]
    Proportion of patients with surgery for nasal polyp

  4. SinoNasal Outcome Test (SNOT-22) score [ Time Frame: Baseline and week 56 ]
    Change in SinoNasal Outcome Test (SNOT-22) score (SNOT-22 can be rated via a 6-point scale (0- No Problem to 5- Problem as bad as it can be)

  5. Patients with systemic corticosteroids use for nasal polyp [ Time Frame: By week 56 ]
    Proportion of patients with systemic corticosteroids use for nasal polyp

  6. First systemic corticosteroids course for nasal polyp [ Time Frame: By week 56 ]
    Time to first systemic corticosteroids course for nasal polyp

  7. Courses of systemic corticosteroids for nasal polyp [ Time Frame: By week 56 ]
    Number of courses of systemic corticosteroids for nasal polyp

  8. Total systemic corticosteroids dose used [ Time Frame: By Week 56 ]
    Systemic corticosteroids use for relief of nasal symptoms

  9. Total duration of systemic corticosteroids use for nasal polyp [ Time Frame: By Week 56 ]
    Systemic corticosteroids use for relief of nasal symptoms

  10. Nasal symptom score(s) as captured in the daily diary [ Time Frame: Baseline and week 56 ]
    Change in nasal symptom score(s) as captured in the daily diary (severity of each symptom at its worst can be rated using a 4-point verbal rating scale (0-none to 3-severe) )

  11. University of Pennsylvania Smell Identification Test (UPSIT) score [ Time Frame: Baseline and week 56 ]
    Change in University of Pennsylvania Smell Identification Test score (UPSIT scores are based on number of correctly identified odors (score range 0 to 40), higher scores mean a better outcome.)

  12. Sinus severity score by quantitative CT analysis [ Time Frame: Baseline and week 56 ]
    Change in sinus severity score by Quantitative CT analysis (sinus severity score range from 0 to 100%, higher scores mean a worse outcome)

  13. Zinreich score (modified LMS) [ Time Frame: Baseline and week 56 ]
    Change in Zinreich score (modified LMS) (Zinreich score range from 0-54, higher scores mean a worse outcome.)

  14. Short Form 36-item Health survey, Version 2 (SF-36v2) [ Time Frame: Baseline and week 56 ]
    Change in Short Form 36-item Health survey, Version 2 (SF-36v2), Physical Component Score and Mental Component Score and domains (each item is scored 0-100, with higher scores meaning better outcomes)

  15. Serum trough concentrations [ Time Frame: Week 0, 16, 24, 40, 56, 60, 68, 80. ]
    Summary of serum concentration of benralizumab

  16. Anti-drug antibodies [ Time Frame: Week 0, 16, 24, 40, 56, 60, 68, 80. ]
    Incidence of anti-drug antibodies



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
  2. Subject must be 18 to 75 years of age inclusive, at the time of signing the informed consent form.
  3. Patients with bilateral sinonasal polyps that, despite treatment with standard of care including a history of treatment with Systemic corticosteroids (oral, parenteral) or prior surgery for Nasal polyps have severity consistent with a need for surgery as described by:

    • A minimum total Nasal polyp score of 5 out of a maximum score of 8 (with a unilateral score of at least 2 for each nostril) at Visit 1 and continuously maintained at Visit 2 to meet the randomisation criterion as determined by the study Imaging Core Lab
    • Ongoing symptoms for at least 12 weeks prior to Visit 1
    • Patient-reported moderate to severe nasal blockage (score 2 or 3) over the 2-weeks prior to Visit 1 (2-week recall assessment of symptoms, scores 0-none to 3-severe).
  4. CT Lund Mackay score for ethmoid ≥ maxillary as determined by the study Imaging Core lab.
  5. Patients meet one of the following criteria:

    • Blood eosinophil count > 5% as determined by central lab
    • Blood eosinophil count is >2% and ≤ 5% as determined by central lab with a diagnosis of asthma and/or Aspirin exacerbated respiratory disease or NSAID exacerbated respiratory disease
  6. Patients who are on Intranasal corticosteroids or leukotriene receptor antagonists (LTRAs), need to be at stable dose for at least 30 days prior to Visit 1.
  7. SNOT-22 total score ≥ 20 at enrolment (Visit 1).

Exclusion Criteria:

  1. Patients who have undergone any nasal and/or sinus surgery within 3 months prior to Visit 1.
  2. Patients with conditions or concomitant disease that makes them non evaluable for the co-primary efficacy endpoint such as:

    • Unilateral antrochoanal polyps;
    • Nasal septal deviation that occludes at least one nostril;
    • Acute sinusitis, nasal infection, or upper respiratory infection at screening or in the 2 weeks before screening;
    • Current rhinitis medicamentosa;
    • Allergic fungal rhinosinusitis or allergic fungal sinusitis;
    • Nasal cavity tumours.
  3. Patients experiencing an asthma exacerbation requiring systemic (oral and/or parenteral) corticosteroids treatment or hospitalisation (>24hrs) for treatment of asthma within 4 weeks prior to Visit 1.
  4. Known history of allergy or reaction to any component of the Investigational product formulation.
  5. Prior/concomitant therapy: use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, or any experimental anti-inflammatory therapy) within 3 months prior to V1 and during the study period.
  6. Alanine aminotransferase or aspartate aminotransferase level ≥ 3 times the upper limit of normal.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04157335


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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China
Research Site Not yet recruiting
Beijing, China, 100191
Research Site Not yet recruiting
Beijing, China, 100730
Research Site Not yet recruiting
Changchun, China, 130021
Research Site Not yet recruiting
Changsha, China, 410013
Research Site Not yet recruiting
Chengdu, China, 610072
Research Site Not yet recruiting
Chongqing, China, 400010
Research Site Not yet recruiting
Dalian, China, 116001
Research Site Not yet recruiting
Foshan, China, 528000
Research Site Not yet recruiting
Guangzhou, China, 510180
Research Site Not yet recruiting
Hangzhou, China, 310003
Research Site Not yet recruiting
Jinan, China, 250014
Research Site Not yet recruiting
Nanjing, China, 210029
Research Site Not yet recruiting
Nanning, China, 530021
Research Site Not yet recruiting
Qingdao, China, 266003
Research Site Not yet recruiting
Shanghai, China, 200065
Research Site Not yet recruiting
Shanghai, China, 200092
Research Site Not yet recruiting
Tianjin, China, 300052
Research Site Not yet recruiting
Wuhan, China, 430022
Research Site Not yet recruiting
Xian, China, 710061
Research Site Not yet recruiting
Yantai, China, 264000
Japan
Research Site Recruiting
Chiba-shi, Japan, 262-0015
Research Site Recruiting
Hiroshima-shi, Japan, 734-8551
Research Site Recruiting
Ichikawa-shi, Japan, 272-0143
Research Site Recruiting
Kawasaki-shi, Japan, 211-0063
Research Site Recruiting
Kumamoto-shi, Japan, 860-0814
Research Site Recruiting
Meguro-ku, Japan, 153-0061
Research Site Recruiting
Meguro-ku, Japan, 153-8515
Research Site Not yet recruiting
Minato-ku, Japan, 105-8471
Research Site Not yet recruiting
Moriguchi-shi, Japan, 570-0074
Research Site Recruiting
Osaka-shi, Japan, 540-0008
Research Site Recruiting
Yoshida-gun, Japan, 910-1193
Thailand
Research Site Recruiting
Bangkok, Thailand, 10330
Research Site Recruiting
Bangkok, Thailand, 10400
Research Site Recruiting
Bangkok, Thailand, 10700
Research Site Recruiting
Chiang Mai, Thailand, 50200
Research Site Recruiting
Khon Kaen, Thailand, 40002
Vietnam
Research Site Not yet recruiting
Hanoi, Vietnam
Research Site Not yet recruiting
Ho Chi Minh City, Vietnam, 70000
Research Site Not yet recruiting
Ho Chi Minh, Vietnam, 700000
Research Site Not yet recruiting
Ho Chi Minh, Vietnam, 70000
Research Site Not yet recruiting
Hochiminh, Vietnam, 700000
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Luo Zhang, Prof. Dr. Beijing Tongren Hospital
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04157335    
Other Study ID Numbers: D3252C00002
First Posted: November 8, 2019    Key Record Dates
Last Update Posted: March 25, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by AstraZeneca:
Benralizumab
Nasal Polyposis
Eosinophilic Chronic Rhinosinusitis with Nasal Polyposis
Nasal Polyps
Additional relevant MeSH terms:
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Nasal Polyps
Polyps
Pathological Conditions, Anatomical
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Benralizumab
Anti-Asthmatic Agents
Respiratory System Agents