Conjunctivitis, Rhinitis Allergic
Conditions
Brief summary
This is a study to evaluate the efficacy and safety of grass sublingual tablet (SCH 697243) versus placebo in the treatment of grass pollen-induced allergic hayfever symptoms. Participants will receive either the sublingual grass tablet or a placebo tablet during the study. It is expected that those participants receiving the active sublingual grass tablet will have less hayfever symptoms and need less medications to treat hayfever symptoms during the grass pollen season.
Interventions
BIOLOGICALGrass (Phleum pratense) pollen allergen extract
One dissolving tablet sublingually once daily
BIOLOGICALPlacebo for SCH 697243
One dissolving tablet sublingually once daily
Sponsors
ALK-Abelló A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Must have a clinical history of significant allergic rhinoconjunctivitis to grass (with or without asthma) * Must have a positive skin prick test response to Phleum pratense (Timothy grass) * Must be positive for specific immunoglobulin E (IgE) against Phleum pratense (Timothy grass) * Must have an forced expiratory volume in 1 second (FEV1) of at least 70% of predicted value at Screening \- Safety laboratory tests and vital signs conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor
Exclusion criteria
* Has a clinical history of symptomatic seasonal allergic rhinitis and/or asthma due to another allergen during or potentially overlapping the GPS * Has a clinical history of significant symptomatic perennial allergic rhinitis and/or asthma due to an allergen to which the participant is regularly exposed * Has received an immunosuppressive treatment within 3 months prior to the Screening Visit * Has a clinical history of severe asthma * Has a history of anaphylaxis with cardiorespiratory symptoms * Has a history of self-injectable epinephrine use * Has a history of chronic urticaria and angioedema * Has a clinical history of chronic sinusitis during the 2 years prior to the Screening Visit * Has current severe atopic dermatitis * Is breast-feeding, pregnant, or intending to become pregnant * Had previous treatment by immunotherapy with any grass pollen allergen for more than 1 month within the 5 years prior to the Screening Visit * Ongoing treatment with any specific immunotherapy at the time of the Screening Visit * Has a known history of allergy, hypersensitivity or intolerance to the ingredients of the study drug (except for Phleum pratense), rescue medications, or self-injectable epinephrine * Has any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study. Specific examples include but are not limited to hypertension being treated with beta blockers, coronary artery disease, arrhythmia, stroke, ocular conditions requiring topical beta blockers, any condition requiring the use of beta blockers * Has used any investigational drugs within 30 days of the Screening Visit * Is participating in any other clinical study * Is a family member of the investigational study staff conducting this study * Is unable to meet medication washout requirements * Is unlikely to be able to complete the trial, for any reason, or likely to travel for extended periods of time during the GPS, which in the opinion of the investigator will compromise the data * Has a clinically significant abnormal vital sign or laboratory value that would preclude participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Total Combined Rhinoconjunctivitis Daily Symptom Score (DSS) and Rhinoconjunctivitis Daily Medication Score (DMS) Over the Entire Grass Pollen Season (GPS) | Entire GPS (expected average duration of 5 to 6 weeks) | The total combined score was the sum of the rhinoconjunctivitis DSS and rhinoconjunctivitis DMS for the entire GPS (total score range: 0 to 54), with a lower score representing less rhinoconjunctivitis symptoms and use of medications. For rhinoconjunctivitis DSS, participants assessed a total of 6 rhinoconjunctivitis symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes, and watery eyes) each on a scale of 0 to 3 (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms; score range: 0 to 18), with a lower score representing less rhinoconjunctivitis symptoms. For rhinoconjunctivitis DMS, participants reported their use of specific rescue medications with specific scores assigned to each medication (score range: 0 to 36), with a lower score representing less use of medications for rhinoconjunctivitis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Total Combined Rhinoconjunctivitis DSS and Rhinoconjunctivitis DMS Over the Peak GPS | Peak GPS (expected average duration of 2 weeks) | The total combined score was the sum of the rhinoconjunctivitis DSS and rhinoconjunctivitis DMS for the entire GPS (total score range: 0 to 54), with a lower score representing less rhinoconjunctivitis symptoms and use of medications. For rhinoconjunctivitis DSS, participants assessed a total of 6 rhinoconjunctivitis symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes, and watery eyes) each on a scale of 0 to 3 (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms; score range: 0 to 18), with a lower score representing less rhinoconjunctivitis symptoms. For rhinoconjunctivitis DMS, participants reported their use of specific rescue medications with specific scores assigned to each medication (score range: 0 to 36), with a lower score representing less use of medications for rhinoconjunctivitis. |
| Average Rhinoconjunctivitis Quality of Life Questionnaire With Standardized Activities for Participants ≥12 Years of Age (RQLQ12+) Over the Peak GPS | Peak GPS (expected average duration of 2 weeks) | The RQLQ12+ consists of 7 domains: Activities, Sleep, Non-Nose/Eye Symptoms, Practical Problems, Nasal Symptoms, Eye Symptoms, Emotional. Participants reflect on their experience over the previous 7 days and assess 28 items on a scale of 0 to 6 (0=Not troubled, 6=Extremely troubled; score range: 0-6 \[mean of all domain scores\]), with a higher score indicating more significant impairment due to seasonal allergic rhinoconjunctivitis. |
| Average Rhinoconjunctivitis DMS Over the Entire GPS | Entire GPS (expected average duration of 5 to 6 weeks) | For rhinoconjunctivitis DMS, participants reported their use of specific rescue medications with specific scores assigned to each medication (score range: 0 to 36), with a lower score representing less use of medications for rhinoconjunctivitis. |
| Average Rhinoconjunctivitis DSS Over the Entire GPS | Entire GPS (expected average duration of 5 to 6 weeks) | For rhinoconjunctivitis DSS, participants assessed a total of 6 rhinoconjunctivitis symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes, and watery eyes) each on a scale of 0 to 3 (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms; score range: 0 to 18), with a lower score representing less rhinoconjunctivitis symptoms. |
| Average Rhinoconjunctivitis DMS Over the Peak GPS | Peak GPS (expected average duration of 2 weeks) | For rhinoconjunctivitis DMS, participants reported their use of specific rescue medications with specific scores assigned to each medication (score range: 0 to 36), with a lower score representing less use of medications for rhinoconjunctivitis. |
| Average Paediatric Standardised Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Overall Score Over the Peak GPS (Participants 6 to <12 Years of Age) | Peak GPS (expected average duration of 2 weeks) | For PRQLQ, participants assessed a total of 19 items within 5 domains: Nose Symptoms, Eye Symptoms, Practical Problems, Activity Limitation and Other Symptoms, each on a scale of 0 to 6 (0=Not troubled, 6=Extremely troubled; score range: 0 to 6 \[mean of all domain scores\]), with a higher score indicating more significant impairment due to seasonal allergic rhinoconjunctivitis. |
| Average Rhinoconjunctivitis DSS Over the Peak GPS | Peak GPS (expected average duration of 2 weeks) | For rhinoconjunctivitis DSS, participants assessed a total of 6 rhinoconjunctivitis symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes, and watery eyes) each on a scale of 0 to 3 (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms; score range: 0 to 18), with a lower score representing less rhinoconjunctivitis symptoms. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SCH 697243 Participants receiving Grass (Phleum pratense) Pollen Allergen Extract | 752 |
| Placebo Participants receiving Placebo | 749 |
| Total | 1,501 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 2 | 2 |
| Overall Study | Adverse Event | 54 | 19 |
| Overall Study | Lost to Follow-up | 16 | 16 |
| Overall Study | Protocol Violation | 25 | 21 |
| Overall Study | Withdrawal by Subject | 52 | 39 |
Baseline characteristics
| Characteristic | SCH 697243 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 32.9 years STANDARD_DEVIATION 14.5 | 33.5 years STANDARD_DEVIATION 14.5 | 33.2 years STANDARD_DEVIATION 14.5 |
| Gender Female | 381 Participants | 333 Participants | 714 Participants |
| Gender Male | 371 Participants | 416 Participants | 787 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 480 / 753 | 316 / 745 |
| serious Total, serious adverse events | 14 / 753 | 9 / 745 |
Outcome results
Primary
Average Total Combined Rhinoconjunctivitis Daily Symptom Score (DSS) and Rhinoconjunctivitis Daily Medication Score (DMS) Over the Entire Grass Pollen Season (GPS)
The total combined score was the sum of the rhinoconjunctivitis DSS and rhinoconjunctivitis DMS for the entire GPS (total score range: 0 to 54), with a lower score representing less rhinoconjunctivitis symptoms and use of medications. For rhinoconjunctivitis DSS, participants assessed a total of 6 rhinoconjunctivitis symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes, and watery eyes) each on a scale of 0 to 3 (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms; score range: 0 to 18), with a lower score representing less rhinoconjunctivitis symptoms. For rhinoconjunctivitis DMS, participants reported their use of specific rescue medications with specific scores assigned to each medication (score range: 0 to 36), with a lower score representing less use of medications for rhinoconjunctivitis.
Time frame: Entire GPS (expected average duration of 5 to 6 weeks)
Population: The Full Analysis Set (FAS) population consisted of all randomized participants who received at least one dose of study drug and had at least one post-treatment observation for the analysis endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCH 697243 | Average Total Combined Rhinoconjunctivitis Daily Symptom Score (DSS) and Rhinoconjunctivitis Daily Medication Score (DMS) Over the Entire Grass Pollen Season (GPS) | 3.24 score on a scale |
| Placebo | Average Total Combined Rhinoconjunctivitis Daily Symptom Score (DSS) and Rhinoconjunctivitis Daily Medication Score (DMS) Over the Entire Grass Pollen Season (GPS) | 4.22 score on a scale |
p-value: <0.00195% CI: [-1.2, -0.4]Wilcoxon Rank Sum Test
Secondary
Average Paediatric Standardised Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Overall Score Over the Peak GPS (Participants 6 to <12 Years of Age)
For PRQLQ, participants assessed a total of 19 items within 5 domains: Nose Symptoms, Eye Symptoms, Practical Problems, Activity Limitation and Other Symptoms, each on a scale of 0 to 6 (0=Not troubled, 6=Extremely troubled; score range: 0 to 6 \[mean of all domain scores\]), with a higher score indicating more significant impairment due to seasonal allergic rhinoconjunctivitis.
Time frame: Peak GPS (expected average duration of 2 weeks)
Population: The FAS population consisted of all randomized participants \<12 years of age who received at least one dose of study drug and had at least one post-treatment observation for the analysis endpoint.entry.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCH 697243 | Average Paediatric Standardised Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Overall Score Over the Peak GPS (Participants 6 to <12 Years of Age) | 0.89 score on a scale |
| Placebo | Average Paediatric Standardised Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Overall Score Over the Peak GPS (Participants 6 to <12 Years of Age) | 0.75 score on a scale |
p-value: 0.64495% CI: [-0.4, 0.6]Wilcoxon Rank Sum Test
Secondary
Average Rhinoconjunctivitis DMS Over the Entire GPS
For rhinoconjunctivitis DMS, participants reported their use of specific rescue medications with specific scores assigned to each medication (score range: 0 to 36), with a lower score representing less use of medications for rhinoconjunctivitis.
Time frame: Entire GPS (expected average duration of 5 to 6 weeks)
Population: The FAS population consisted of all randomized participants who received at least one dose of study drug and had at least one post-treatment observation for the analysis endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCH 697243 | Average Rhinoconjunctivitis DMS Over the Entire GPS | 0.88 score on a scale | Standard Error 0.11 |
| Placebo | Average Rhinoconjunctivitis DMS Over the Entire GPS | 1.36 score on a scale | Standard Error 0.16 |
p-value: 0.000395% CI: [-0.73, -0.22]Zero-Inflated Log-Normal Model
Secondary
Average Rhinoconjunctivitis DMS Over the Peak GPS
For rhinoconjunctivitis DMS, participants reported their use of specific rescue medications with specific scores assigned to each medication (score range: 0 to 36), with a lower score representing less use of medications for rhinoconjunctivitis.
Time frame: Peak GPS (expected average duration of 2 weeks)
Population: The FAS population consisted of all randomized participants who received at least one dose of study drug and had at least one post-treatment observation for the analysis endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCH 697243 | Average Rhinoconjunctivitis DMS Over the Peak GPS | 1.01 score on a scale | Standard Error 0.13 |
| Placebo | Average Rhinoconjunctivitis DMS Over the Peak GPS | 1.63 score on a scale | Standard Error 0.19 |
p-value: 0.000195% CI: [-0.94, -0.31]Zero-Inflated Log-Normal Model
Secondary
Average Rhinoconjunctivitis DSS Over the Entire GPS
For rhinoconjunctivitis DSS, participants assessed a total of 6 rhinoconjunctivitis symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes, and watery eyes) each on a scale of 0 to 3 (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms; score range: 0 to 18), with a lower score representing less rhinoconjunctivitis symptoms.
Time frame: Entire GPS (expected average duration of 5 to 6 weeks)
Population: The FAS population consisted of all randomized participants who received at least one dose of study drug and had at least one post-treatment observation for the analysis endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCH 697243 | Average Rhinoconjunctivitis DSS Over the Entire GPS | 2.49 score on a scale |
| Placebo | Average Rhinoconjunctivitis DSS Over the Entire GPS | 3.13 score on a scale |
p-value: 0.00195% CI: [-0.7, -0.2]Wilcoxon Rank Sum Test
Secondary
Average Rhinoconjunctivitis DSS Over the Peak GPS
For rhinoconjunctivitis DSS, participants assessed a total of 6 rhinoconjunctivitis symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes, and watery eyes) each on a scale of 0 to 3 (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms; score range: 0 to 18), with a lower score representing less rhinoconjunctivitis symptoms.
Time frame: Peak GPS (expected average duration of 2 weeks)
Population: The FAS population consisted of all randomized participants who received at least one dose of study drug and had at least one post-treatment observation for the analysis endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCH 697243 | Average Rhinoconjunctivitis DSS Over the Peak GPS | 2.71 score on a scale |
| Placebo | Average Rhinoconjunctivitis DSS Over the Peak GPS | 3.40 score on a scale |
p-value: <0.00195% CI: [-0.9, -0.2]Wilcoxon Rank Sum Test
Secondary
Average Rhinoconjunctivitis Quality of Life Questionnaire With Standardized Activities for Participants ≥12 Years of Age (RQLQ12+) Over the Peak GPS
The RQLQ12+ consists of 7 domains: Activities, Sleep, Non-Nose/Eye Symptoms, Practical Problems, Nasal Symptoms, Eye Symptoms, Emotional. Participants reflect on their experience over the previous 7 days and assess 28 items on a scale of 0 to 6 (0=Not troubled, 6=Extremely troubled; score range: 0-6 \[mean of all domain scores\]), with a higher score indicating more significant impairment due to seasonal allergic rhinoconjunctivitis.
Time frame: Peak GPS (expected average duration of 2 weeks)
Population: The FAS population consisted of all randomized participants ≥12 years of age who received at least one dose of study drug and had at least one post-treatment observation for the analysis endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCH 697243 | Average Rhinoconjunctivitis Quality of Life Questionnaire With Standardized Activities for Participants ≥12 Years of Age (RQLQ12+) Over the Peak GPS | 0.93 score on a scale |
| Placebo | Average Rhinoconjunctivitis Quality of Life Questionnaire With Standardized Activities for Participants ≥12 Years of Age (RQLQ12+) Over the Peak GPS | 1.06 score on a scale |
p-value: 0.02795% CI: [-0.2, 0]Wilcoxon Rank Sum Test
Secondary
Average Total Combined Rhinoconjunctivitis DSS and Rhinoconjunctivitis DMS Over the Peak GPS
The total combined score was the sum of the rhinoconjunctivitis DSS and rhinoconjunctivitis DMS for the entire GPS (total score range: 0 to 54), with a lower score representing less rhinoconjunctivitis symptoms and use of medications. For rhinoconjunctivitis DSS, participants assessed a total of 6 rhinoconjunctivitis symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes, and watery eyes) each on a scale of 0 to 3 (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms; score range: 0 to 18), with a lower score representing less rhinoconjunctivitis symptoms. For rhinoconjunctivitis DMS, participants reported their use of specific rescue medications with specific scores assigned to each medication (score range: 0 to 36), with a lower score representing less use of medications for rhinoconjunctivitis.
Time frame: Peak GPS (expected average duration of 2 weeks)
Population: The FAS population consisted of all randomized participants who received at least one dose of study drug and had at least one post-treatment observation for the analysis endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCH 697243 | Average Total Combined Rhinoconjunctivitis DSS and Rhinoconjunctivitis DMS Over the Peak GPS | 3.33 score on a scale |
| Placebo | Average Total Combined Rhinoconjunctivitis DSS and Rhinoconjunctivitis DMS Over the Peak GPS | 4.67 score on a scale |
p-value: <0.00195% CI: [-1.4, -0.5]Wilcoxon Rank Sum Test