Clinical Trial Results:
A randomised, parallel-group, double-blind, placebo-controlled phase III trial assessing the efficacy and safety of 5-grass mix SLIT-drops in adults with grass pollen-induced rhinoconjunctivitis
Summary
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EudraCT number |
2020-000455-12 |
Trial protocol |
EE LT LV CZ PL FR |
Global end of trial date |
26 Sep 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Oct 2024
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First version publication date |
12 Oct 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SU-G-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04881461 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
ALK-Abelló A/S
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Sponsor organisation address |
Bøge Allé 6-8, Hørsholm, Denmark, 2970
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Public contact |
Senior Director, Clinical Data Science, Global Clinical Development, ALK-Abelló A/S, +45 45747576, clinicaltrials@alk.net
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Scientific contact |
Senior Director, Clinical Data Science, Global Clinical Development, ALK-Abelló A/S, +45 45747576, clinicaltrials@alk.net
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Oct 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Sep 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Sep 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the efficacy of 5-grass mix SLIT-drops (sublingual immunotherapy) to placebo in relieving grass rhinoconjunctivitis symptoms and in use of symptom-relief medication during the 2nd Peak Grass Pollen Season (PGPS)
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Protection of trial subjects |
Safety surveillance.
Access to rescue/reliever medication.
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Background therapy |
Rhinoconjunctivitis rescue medication: Subjects were provided with rescue medication (antihistamine/nasal corticosteroid) to relieve rhinoconjunctivitis symptoms. The rescue medication was provided before the start of the grass pollen season and could be used as needed in accordance with the label. The subjects were instructed to start with antihistamine and continue with nasal corticosteroids only if antihistamine could not alleviate the symptoms. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 May 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 233
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Country: Number of subjects enrolled |
Czechia: 113
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Country: Number of subjects enrolled |
Estonia: 2
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Country: Number of subjects enrolled |
France: 13
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Country: Number of subjects enrolled |
Latvia: 33
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Country: Number of subjects enrolled |
Lithuania: 51
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Worldwide total number of subjects |
445
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EEA total number of subjects |
445
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
445
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were recruited from 45 sites in 6 countries (Poland, Czechia, Estonia, France, Latvia and Lithuania). First subject first visit: 10-May-2021 Last subject last visit/contact: 26-Sep-2023 | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
*Male or female aged ≥18 years *Clinical history of grass pollen-induced allergic rhinoconjunctivitis for ≥2 years (with or without asthma), which was severe and remained troublesome despite treatment with symptom-relieving medication during the previous grass pollen season. *Positive SPT and specific IgE against Phleum pratense | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
Placebo | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution in single-dose container
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Routes of administration |
Sublingual use
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Dosage and administration details |
Subjects were instructed to take IMP once daily and that eating and drinking should be avoided for the next 5 minutes. The entire content of the single-dose container should be placed under the tongue (sublingual) and swallowing should be avoided for 2 minutes.
The first administration of IMP was done at the clinic under medical supervision with a subsequent 30-minute observation period.
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Arm title
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5-grass mix SLIT-drops | |||||||||||||||||||||||||||
Arm description |
5-grass mix SLIT-drops | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
5-grass mix SLIT-drops
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution in single-dose container
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Routes of administration |
Sublingual use
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Dosage and administration details |
Subjects were instructed to take IMP once daily and that eating and drinking should be avoided for the next 5 minutes. The entire content of the single-dose container should be placed under the tongue (sublingual) and swallowing should be avoided for 2 minutes.
The first administration of IMP was done at the clinic under medical supervision with a subsequent 30-minute observation period.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo | ||||||||||||||||||||||||||||||||||||
Reporting group title |
5-grass mix SLIT-drops
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Reporting group description |
5-grass mix SLIT-drops | ||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Full analysis set, defined as all randomised subjects. Subjects were analysed as randomised i.e., according to their randomised assignment of treatment.
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Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Safety analysis set definded as all randomised subjects who received at least one dose of IMP. Subjects were analysed as treated i.e., according to treatment they actually received.
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo | ||
Reporting group title |
5-grass mix SLIT-drops
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Reporting group description |
5-grass mix SLIT-drops | ||
Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full analysis set, defined as all randomised subjects. Subjects were analysed as randomised i.e., according to their randomised assignment of treatment.
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Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety analysis set definded as all randomised subjects who received at least one dose of IMP. Subjects were analysed as treated i.e., according to treatment they actually received.
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End point title |
Average daily allergic rhinoconjunctivitis total combined score (TCS) during the 2nd peak grass pollen season (PGPS) | ||||||||||||
End point description |
The average daily TCS evaluates the treatment effect based on reduction in daily rhinoconjunctivitis symptoms and in use of symptom-relieving medication (on a scale from 0 to 38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 2nd PGPS.
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End point type |
Primary
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End point timeframe |
During the 2nd PGPS (14 days)
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Statistical analysis title |
Trial product estimand - Main estimator | ||||||||||||
Statistical analysis description |
The endpoint was analysed using primary (trial product) estimand. The null hypothesis was defined as "no differences in means between treatment arms". The endpoint analysis was based on a 5% significance level. The endpoint was analysed using a linear mixed effects model with the following covariates: treatment, season and their interaction, ongoing asthma status, and country and season interaction.
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Comparison groups |
Placebo v 5-grass mix SLIT-drops
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Number of subjects included in analysis |
379
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0036 [1] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Absolute difference | ||||||||||||
Point estimate |
1.88
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.6 | ||||||||||||
upper limit |
3.17 | ||||||||||||
Notes [1] - Adjusted p-value |
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End point title |
Average weekly overall rhinoconjunctivitis quality of life questionnaire (RQLQ) score during the 2nd peak grass pollen season (PGPS) | ||||||||||||
End point description |
The RQLQ measures the rhinoconjunctivitis quality of life. The RQLQ contains 28 questions, each scored on a 7-point scale (0 = not impaired at all; 6 = severely impaired). The overall RQLQ score is a mean of the 28 questions. Higher scores indicate worse quality of life. The endpoint is calculated as the average score of all reported weekly values during the 2nd PGPS.
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End point type |
Secondary
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End point timeframe |
During the 2nd PGPS (14 days)
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Statistical analysis title |
Trial product estimand - Main estimator | ||||||||||||
Statistical analysis description |
The endpoint was analysed using primary (trial product) estimand. The null hypothesis was defined as "no differences in means between treatment arms". The endpoint analysis was based on a 5% significance level. The endpoint was analysed using a linear mixed effects model with the following covariates: treatment, season and their interaction, ongoing asthma status, and country and season interaction.
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Comparison groups |
Placebo v 5-grass mix SLIT-drops
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Number of subjects included in analysis |
369
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.1111 [2] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Absolute difference | ||||||||||||
Point estimate |
0.17
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.04 | ||||||||||||
upper limit |
0.39 | ||||||||||||
Notes [2] - Adjusted p-value |
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End point title |
Average daily allergic rhinoconjunctivitis total combined score (TCS) during the 1st peak grass pollen season (PGPS) | ||||||||||||
End point description |
The average daily TCS evaluates the treatment effect based on reduction in daily rhinoconjunctivitis symptoms and in use of symptom-relieving medication (on a scale from 0 to 38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 1st PGPS.
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End point type |
Secondary
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End point timeframe |
During the 1st PGPS (14 days)
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Statistical analysis title |
Trial product estimand - Main estimator | ||||||||||||
Statistical analysis description |
The endpoint was analysed using primary (trial product) estimand. The null hypothesis was defined as "no differences in means between treatment arms". The endpoint analysis was based on a 5% significance level. The endpoint was analysed using a linear mixed effects model with the following covariates: treatment, season and their interaction, ongoing asthma status, and country and season interaction.
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Comparison groups |
Placebo v 5-grass mix SLIT-drops
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Number of subjects included in analysis |
410
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0417 [3] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Absolute difference | ||||||||||||
Point estimate |
1.33
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.01 | ||||||||||||
upper limit |
2.67 | ||||||||||||
Notes [3] - Observed p-value |
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End point title |
Average weekly overall rhinoconjunctivitis quality of life questionnaire (RQLQ) score during the 1st peak grass pollen season (PGPS) | ||||||||||||
End point description |
The RQLQ measures the rhinoconjunctivitis quality of life. The RQLQ contains 28 questions, each scored on a 7-point scale (0 = not impaired at all; 6 = severely impaired). The overall RQLQ score is a mean of the 28 questions. Higher scores indicate worse quality of life. The endpoint is calculated as the average score of all reported weekly values during the 1st PGPS.
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End point type |
Secondary
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End point timeframe |
During the 1st PGPS (14 days)
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Statistical analysis title |
Trial product estimand - Main estimator | ||||||||||||
Statistical analysis description |
The endpoint was analysed using primary (trial product) estimand. The null hypothesis was defined as "no differences in means between treatment arms". The endpoint analysis was based on a 5% significance level. The endpoint was analysed using a linear mixed effects model with the following covariates: treatment, season and their interaction, ongoing asthma status, and country and season interaction.
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Comparison groups |
Placebo v 5-grass mix SLIT-drops
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Number of subjects included in analysis |
402
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.4984 [4] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Absolute difference | ||||||||||||
Point estimate |
0.08
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.15 | ||||||||||||
upper limit |
0.3 | ||||||||||||
Notes [4] - Observed p-value |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AEs) were collected from informed consent to last follow-up contact with subject. Only treatment-emergent AEs are presented, i.e. AEs starting on/after time of first IMP administration and no later than 7 days after last IMP administration
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
5-grass mix SLIT-drops
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Reporting group description |
5-grass mix SLIT-drops | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Nov 2021 |
The amendment was issued after first subject first visit and prior to unblinding. The main changes were:
1. Visit windows changed from 7 to 14 days for the pre-EGPS visits (V4 and V7).
2. A telephone contact between randomisation (V2) and 1st off-season visit (V3) was changed to optional.
3. The definition of end of trial changed from the last subject last physical visit to the last subject follow-up telephone contact.
4. Restricted and prohibited concomitant medication was updated to only include those medications that would impact the safety of the subject and significantly impact the endpoints.
5. Medical history re. asthma: it was clarified that only subjects diagnosed/treated in adulthood should be stratified as asthmatic.
6. Additional specification of events of special interest form and procedure (administrative).
7. Updated contact info on laboratory due to change of vendor.
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |