ANCHOR-1

JRCT ID: jRCT2061220020

Registered date:28/05/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Chronic rhinosinusitis with nasal polyps
• Date of first enrollment: 07/07/2022
• Target sample size: 250
• Countries of recruitment: Netherlands,Japan,Germany,Japan,France,Japan,China,Japan,United States,Japan,United Kingdom,Japan,Argentina,Japan,Canada,Japan,Belgium,Japan
• Study type: Interventional

Intervention(s)

This is a study of depemokimab 100 mg + SoC in approximately 250 adults with CRSwNP.
The study will include a 4-week run-in period followed by randomisation to a 52-week treatment period as a double-blind, placebo-controlled phase. The total study duration will be approximately 56 weeks. Randomization will be stratified based on occurrence of previous surgery for nasal polyps and country. Participants will be randomised in a 1:1 ratio into one of the two treatment groups, receiving 100 mg of depemokimab SC or placebo (both in addition to SoC) for a total of two doses (26 weeks apart).
Throughout the entire study period (run-in + treatment period), participants will be on the SoC for CRSwNP.

Outcome(s)

Primary Outcome

-Change from baseline in total endoscopic NP score at Week 52 (centrally read)
-Change from baseline in mean nasal obstruction score (verbal response scale [VRS]) from Week 49 through to Week 52

Secondary Outcome

-Change from baseline in mean symptom score for rhinorrhoea (runny nose) (VRS) from Week 49 through to Week 52
-Change from baseline in mean symptom score for loss of smell (VRS) from Week 49 through to Week 52
-Change from baseline in Lund Mackay CT score at Week 52
-Change from baseline in SNOT-22 total score at Week 52
-Change from baseline in Asthma Control Questionnaire (ACQ-5) score at Week 52 in participants with an ACQ-5 score >0.75 at baseline
-Change from baseline in mean nasal obstruction score (VRS) from Week 21 through to Week 24
-Change from baseline in total endoscopic NP score at Week 26

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.18 years of age and older inclusive, at the time of signing the informed consent.
2.Endoscopic bilateral Nasal Polyps (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
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 8 weeks prior to
screening.
5.Participants with severe NP symptoms defined as symptoms of nasal congestion/blockade/obstruction with moderate or severe severity (VRS (Verbal response scale) score of 2 or 3) and loss of smell or rhinorrhoea (runny nose)
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
7.Male or eligible female participants.

Exclude criteria

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 toelevated 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.
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.
18.Other Concurrent Medical Conditions: Participants who have known, preexisting, 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, 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 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant should remain symptom-free. Reported smell/ taste complications from COVID-19 must be used as exclusion.
22.Participants that have been exposed to ionising radiation in excess of 10mSv above background over the previous 3-year period as a result of occupational exposure or previous participation in research studies.
23.Previous participation: Previously participated in any study with mepolizumab, reslizumab, or benralizumab and received study intervention (including placebo) within 12 months prior to Visit 1.
24.Women who are pregnant or lactating or are planning on becoming pregnant during the study.

Related Information

• Primary Sponsor: Sugiyama Yutaro
• Secondary ID(s): NCT05274750