Primary objective:To evaluate the efficacy of depemokimab 100mg SC + SoC compared to placebo + SoC at Week 52 in participants with a diagnosis of CRSwNP.Secondary Objectives:To evaluate the efficacy of depemokimab 100 mg SC + SoC compared to placebo…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
- Upper respiratory tract disorders (excl infections)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
c) Change from baseline in total endoscopic NP score at Week 52 (centrally read)
a) 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 mean nasal obstruction score (VRS) from Week 21
through to Week 24
• Change from baseline in total endoscopic NP score at Week 26
Background summary
Nasal polyposis (NP) is a chronic inflammatory disease of the nasal passage
linings and/or sinuses leading to soft tissue growth in the upper nasal cavity.
The resultant swellings which can grow in both nostrils (bilateral), greatly
impact a patient*s health-related quality of life through increases in nasal
obstruction, loss of smell, facial pain, facial pressure and nasal discharge.
The persistence of these symptoms due to NP leads to CRS. The condition is
therefore also described as CRS with NP (CRSwNP). The European Position Paper
on Rhinosinusitis and NP defines the severity of disease using a total severity
visual analogue scale (VAS) in which a patient is asked to indicate on a 10 cm
VAS how troublesome they consider their symptoms. An overall VAS symptom score
of 0-3 is defined as mild disease, >3-7 as moderate and >7-10 as severe.
Symptoms are invariably accompanied with findings of inflammation of the nasal
mucosa and the presence of a polyp seen through nasal endoscopy or positive
imaging findings, for example using computerized tomography (CT). The aetiology
of CRSwNP is currently unknown.
The current SoC for CRSwNP is treatment with saline washes, INCS and, for
severe symptoms, when short term relief is required, intermittent courses of
systemic corticosteroids. Antibiotic courses may also be required for
intercurrent sinus infection, which often complicates severe NP. Although many
patients with CRSwNP can be adequately controlled with simple medical care
(INCS and oral corticosteroid [OCS], occasional nasal douching and antibiotic
courses), progression to surgery as a result of severe symptoms and disruption
to quality of life is common. Surgery, when ultimately indicated, involves the
removal of the polyp tissue and diseased mucosa, restoring aeration of the
nasal passage and sinuses. Over 250,000 NP surgeries are performed in the US
annually. However, polyps have a strong tendency to recur, often requiring
repeat surgery with a timescale that can vary from a few months to years. Data
suggests patients with NP associated with tissue eosinophilia constitute the
majority of those who have a recurrence after surgery. Repeat (revision)
surgery is associated with diminishing success and a higher potential for
adverse effects, hence alternative treatment options are needed for this
patient group.
While the recurrence of bilateral NP despite surgery is common and known to be
associated with the IL-5/eosinophilic pathway in adults, this is less so for
children. The number of eosinophils and cells expressing messenger RNA for
IL-4, IL-5 and IL-10 is higher in patients with CRS excluding cystic fibrosis
(CF) versus those with CF and controls. Antrochoanal polyps are also another
form of NP more common in children that are usually unilateral and associated
with low eosinophil tissue levels.
Study objective
Primary objective:
To evaluate the efficacy of depemokimab 100mg SC + SoC compared to placebo +
SoC at Week 52 in participants with a diagnosis of CRSwNP.
Secondary Objectives:
To evaluate the efficacy of depemokimab 100 mg SC + SoC compared to placebo +
SoC at Week 52 in terms of symptom scores for rhinorrhoea (runny nose) and loss
of smell.
To evaluate the efficacy of depemokimab 100 mg SC + SoC compared to placebo +
SoC at Week 52 in terms of the Lund Mackay CT score.
To evaluate the efficacy of depemokimab 100 mg SC + SoC compared to placebo +
SoC prior to Week 26 in participants with a diagnosis of CRSwNP.
Study design
This is a randomized, double-blind, placebo-controlled, parallel group, Phase
III study of depemokimab + SoC in adults with CRSwNP. The objective of the
study is to evaluate the efficacy and safety of depemokimab 100 mg,
administered SC by the site staff, via a pre-filled safety syringe device (SSD)
every 6 months + SoC for 52 weeks. Efficacy of depemokimab will be assessed
using co primary endpoints of change from baseline in total endoscopic NP score
at Week 52 and change from baseline in mean nasal obstruction VRS (verbal
response scale) score from Week 49 through to Week 52. Nasal surgery will be
assessed from a pre-specified pooled analysis of study 217095 (this study) and
study 218079.
Intervention
The study will include an approximate 4 week run-in period followed by
randomization to a 52 week treatment period. 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 + SoC or placebo + SoC for a total
of 2 doses (26 weeks apart).
Study burden and risks
• Risks associated with study procedures are listed below.
- When giving blood, participants may feel faint or experience mild pain,
bruising, irritation, or redness from the needle.
- It is possible that the symptoms of participants* condition will not improve
during the study or may even worsen.
- The study drug is given by subcutaneous injection. This means participants
will receive injections in the upper arm or thigh, directly under the skin.
There is a chance participants may feel faint, or experience mild pain,
bruising, irritation, or redness where the needle is placed for each injection.
- During an ECG, small sticky pads are applied to certain parts of participants
body. Some areas on which the patches are placed may need to be shaved.
participants may also feel a small amount of irritation, itching, or redness on
the skin after these pads are removed. This should disappear in a few days.
- During a computerized tomography (CT) scan of participant*s nose and
surrounding area, participants will be exposed to X-ray radiation. It is
thought that exposure to radiation during CT scans could slightly increase your
chances of developing cancer. The additional risk of developing cancer as a
result of this radiation exposure is around 1 in 5000.
- During nasal endoscopy participants might feel discomfort due to the pressure
of the endoscope. Nasal endoscopy is a routine procedure; however, it may have
rare complications like nosebleed, fainting, harmful reaction to the
anaesthetic spray (if physician decides to numb participant*s nose before the
procedure).
Burden:
Participants will be expected to complete 17 visits altogether. The time
between each visit is approximately 4 weeks. The time between Visit 8, Visit 9
and Visit 10 is shorter, there will be approximately 2 weeks between each of
these visits.
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Listed location countries
Age
Inclusion criteria
1. Participant is >=18 years old
2. Participant has a 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
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 must be on daily treatment with INCS (including intranasal
liquid steroid wash/douching) for at least 8 weeks 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
7. Male or eligible female participants:
8. Capable of giving signed informed consent
Exclusion criteria
1. As a result of medical interview, physical examination, or screening
investigation the physician responsible considers the participant unfit for the
study
2. Participants who have cystic fibrosis
3. Participants who have antrochoanal polyps
4. Nasal cavity tumor (malignant or benign)
5. Fungal rhinosinusitis
6. Participant has 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. Participants who have acute sinusitis or upper respiratory tract infection
at screening or in 2 weeks prior to screening
9. Participants who have 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 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. 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. Participants with a known, pre-existing parasitic infestation within 6
months prior to Visit 1
15. Participants with 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. Participants with 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. Participant is ineligible if any of the following hepatic characteristics
are present:
• 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,
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. Participants with allergy/intolerance to the excipients of depemokimab in
Section 6.1, a monoclonal antibody, or biologic.
21. 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
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | - |
| EudraCT | EUCTR2021-005037-16-NL |
| CCMO | NL79949.018.22 |