Investigation of depemokimab (GSK3511294) in patients with chronic rhinosinusitus with nasal polyps (CRSwNP).

Phase 1

• Conditions: Chronic Rhinosinusitis with Nasal Polyps; MedDRA version: 27.0Level: PTClassification code 10080060Term: Chronic rhinosinusitis with nasal polypsSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2021-005037-16-DE
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-28
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply at screening:
AGE
1. 18 years of age and older inclusive, at the time of signing the informed consent.
CRSwNP / ECRS DIAGNOSIS
2. Endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) assessed by the investigator (see Appendix 10)
3.Participants who have had at least one of the following at Visit 1:
• previous nasal surgery for the removal of NP;
• have used at least three consecutive days of systemic corticosteroids in the previous 2 years for the treatment of NP;
• medically unsuitable or intolerant to systemic corticosteroid.
4.Participants (except for those in Japan) must be on daily treatment with INCS (including intranasal liquid steroid wash/douching) for at least the 8 weeks immediately prior to screening.
5.Participants presenting with severe NP symptoms defined as symptoms of nasal congestion/blockade/obstruction with moderate or severe severity and loss of smell or rhinorrhoea (runny nose) based on clinical assessment by the investigator.
6.Presence of symptoms of chronic rhinosinusitis as described by at least 2 different symptoms for at least 12 weeks prior to Visit 1, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), plus
• facial pain/pressure
and/or
•reduction or loss of smell
GENDER
7.Male or eligible female participants:
Female Participants:
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
o Is a woman of non-childbearing potential (WONCBP) as defined in Appendix 4
OR
o Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Appendix 4, from at least 14 days prior to the first dose of study intervention until at least 30 weeks after the last administered dose of study intervention.
• A WOCBP must have a negative highly sensitive serum pregnancy test at Screening Visit 1 and a negative highly sensitive urine pregnancy test within 24 hours before the first dose of study intervention. Additional requirements for pregnancy testing are located in the SoA (Section 1.3).
• Contraceptive use by WOCBP should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention).
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
INFORMED CONSENT
8. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this study protocol.
French participants: In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 240
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY
1.As a result of medical interview, physical examination, or screening investigation the physician responsible considers the participant unfit for the study
2.Cystic fibrosis
3.Antrochoanal polyps
4.Nasal cavity tumor (malignant or benign)
5.Fungal rhinosinusitis
6.Severe nasal septal deviation occluding one nostril preventing full assessment of nasal polyps in both nostrils
7.Participants who had a sino-nasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of nasal polyp score
8.Acute sinusitis or upper respiratory tract infection (URTI) at screening or in 2 weeks prior to screening
9.Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis)
10.Participants who have had an asthma exacerbation requiring admission to hospital within 4 weeks of Screening
11.Participants who have undergone any intranasal and/or sinus surgery (for example polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior to Visit 1; nasal biopsy prior to Visit 1 for diagnostic purposes only is excepted.
12.Participants where NP surgery is contraindicated in the opinion of the Investigator
13.Eosinophilic Diseases: Participants with other conditions that could lead to elevated eosinophils such as hyper-eosinophilic syndromes including (but not limited to) EGPA (formerly known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis
14.Parasitic infection: Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1
15.Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids (CSs) taken as therapy for asthma
16.Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (NOTE:Participants that had localised carcinoma of the skin which was resected for cure will not be excluded).
17.Liver Disease:
•Alanine aminotransferase (ALT) >2x ULN
•Total bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
•Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice.
NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C) are acceptable if participant otherwise meets entry criteria.
18.Other Concurrent Medical Conditions: Participants who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
19.Vasculitis: Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrolment.
20.Hypersensitivity: Participants with allergy/intolerance to the excipients of depemokimab in Section 6.1, a monoclonal antibody, or biologic.
21.COVID-19: Participants that, according to the investigator's medical judgment, are likely to have active COVID-19 infection must be excluded. Participants with known COVID-19

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified