Conjunctivitis, Rhinitis; Allergic, With Asthma
Conditions
Brief summary
This study will evaluate the efficacy and safety of ragweed sublingual tablet (SCH 39641/MK-3641) compared with placebo in participants with ragweed-induced rhinoconjunctivitis over a one-year period. It is expected that ragweed allergic participants on one of the active arms of the trial will have decreased allergic rhinoconjunctivitis symptoms and require less allergy rescue medications during ragweed pollen season.
Interventions
BIOLOGICALSCH 39641 6 Amb a 1-U
SCH 39641 6 Amb a 1-U sublingual tablets administered once daily
BIOLOGICALSCH 39641 12 Amb a 1-U
SCH 39641 12 Amb a 1-U sublingual tablets administered once daily
BIOLOGICALPlacebo
matching placebo sublingual tablets administered once daily
Sponsors
ALK-Abelló A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Must have a clinical history of significant ragweed-induced allergic rhinoconjunctivitis of at least 2 years duration, with or without asthma and have received treatment during the previous RS. * Must have a positive skin prick test response to Ambrosia artemisiifolia at Screening Visit. * Must be positive for specific immunoglobulin E (IgE) against Ambrosia artemisiifolia at Screening Visit. * Must have an forced expiratory volume in 1 second (FEV1) of at least 70% of predicted at Screening Visit. * 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
* Clinical history of symptomatic seasonal allergic rhinitis and/or asthma having received regular medication, due to another allergen during or potentially overlapping the RS. * Clinical history of significant symptomatic perennial allergic rhinitis and/or asthma due to an allergen to which the participant is regularly exposed. * Receipt of an immunosuppressive treatment within 3 months prior to the Screening Visit (except steroids for allergic and asthma symptoms). * Clinical history of severe asthma. * Asthma requiring medium or high dose inhaled corticosteroids. * History of anaphylaxis with cardiorespiratory symptoms. * History of chronic urticaria and angioedema. * Clinical history of chronic sinusitis 2 years prior to the Screening Visit. * Current severe atopic dermatitis. * Breast-feeding, pregnant, or intending to become pregnant. * Had previous treatment by immunotherapy with ragweed allergen or any other allergen 5 years prior to Screening Visit. * History of allergy, hypersensitivity or intolerance to the ingredients of the investigational medicinal products (except for Ambrosia artemisiifolia), rescue medications, or self-injectable epinephrine. * History of self-injectable epinephrine use.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Combined (Sum of) Rhinoconjunctivitis Daily Symptom Score (DSS) and Daily Medication Score (DMS) Averaged Over the Peak Ragweed Season (RS) | The 15-day period during the ragweed season with the highest moving pollen average | The total combined score is a composite endpoint that combines the rhinoconjuntivitis DSS and the rhinoconjunctivitis DMS. The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18). Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medicationwith different rescue medications being assigned different scores/dose unit. The maximum rhinoconjunctivitis DMS score was 36. The sum of the rhinoconjunctivitis DSS and DMS could range from 0 to 54, with a lower score indicating less rhinoconjuntivitis symptoms and medication use. Raw means for DSS+DMS were converted to adjusted means based on an analysis of variance (ANOVA) model with baseline asthmatic condition, pollen region and treatment group as fixed effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Combined Rhinoconjunctivitis DSS and DMS Over the Entire RS | Approximately 5 weeks | The total combined score is a composite endpoint that combines the rhinoconjuntivitis DSS and the rhinoconjunctivitis DMS. The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18). Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medicationwith different rescue medications being assigned different scores/dose unit. The maximum rhinoconjunctivitis DMS score was 36. The sum of the rhinoconjunctivitis DSS and DMS could range from 0 to 54, with a lower score indicating less rhinoconjuntivitis symptoms and medication use. Raw means for DSS+DMS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects. |
| Average Rhinoconjunctivitis DSS for the Peak RS | The 15-day period during the ragweed season with the highest moving pollen average | The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18), with a lower score indicating less rhinoconjuntivitis symptoms. Raw means for DSS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects. |
| Average Rhinoconjunctivitis DSS for the Entire RS | Approximately 5 weeks | The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18), with a lower score indicating less rhinoconjuntivitis symptoms. Raw means for DSS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects. |
| Average Rhinoconjunctivitis DMS for the Peak RS | The 15-day period during the ragweed season with the highest moving pollen average | Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medicationwith different rescue medications being assigned different scores/dose unit. The maximum rhinoconjunctivitis DMS score was 36, with a lower score indicating less rhinoconjuntivitis medication use. Raw means for DMS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SCH 39641 6 Amb a 1-U Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | 190 |
| SCH 39641 12 Amb a 1-U Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | 187 |
| Placebo Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | 188 |
| Total | 565 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative | 2 | 1 | 2 |
| Overall Study | Adverse Event | 15 | 19 | 3 |
| Overall Study | Did not meet protocol eligibility | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 11 | 1 | 7 |
| Overall Study | Noncompliance with protocol | 7 | 7 | 10 |
| Overall Study | Withdrawal by Subject | 22 | 14 | 20 |
Baseline characteristics
| Characteristic | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 35.3 years STANDARD_DEVIATION 9 | 34.9 years STANDARD_DEVIATION 9.41 | 35.9 years STANDARD_DEVIATION 9.13 | 35.4 years STANDARD_DEVIATION 9.17 |
| Gender Female | 84 Participants | 109 Participants | 93 Participants | 286 Participants |
| Gender Male | 106 Participants | 78 Participants | 95 Participants | 279 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 124 / 188 | 136 / 186 | 93 / 186 |
| serious Total, serious adverse events | 2 / 188 | 3 / 186 | 4 / 186 |
Outcome results
Primary
Combined (Sum of) Rhinoconjunctivitis Daily Symptom Score (DSS) and Daily Medication Score (DMS) Averaged Over the Peak Ragweed Season (RS)
The total combined score is a composite endpoint that combines the rhinoconjuntivitis DSS and the rhinoconjunctivitis DMS. The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18). Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medicationwith different rescue medications being assigned different scores/dose unit. The maximum rhinoconjunctivitis DMS score was 36. The sum of the rhinoconjunctivitis DSS and DMS could range from 0 to 54, with a lower score indicating less rhinoconjuntivitis symptoms and medication use. Raw means for DSS+DMS were converted to adjusted means based on an analysis of variance (ANOVA) model with baseline asthmatic condition, pollen region and treatment group as fixed effects.
Time frame: The 15-day period during the ragweed season with the highest moving pollen average
Population: The Full Analysis Set (FAS) population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement. A total of 5 participants at one site were excluded from all efficacy analyses due to Good Clinical Practice (GCP) issues.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCH 39641 6 Amb a 1-U | Combined (Sum of) Rhinoconjunctivitis Daily Symptom Score (DSS) and Daily Medication Score (DMS) Averaged Over the Peak Ragweed Season (RS) | 6.70 score on a scale | Standard Error 0.563 |
| SCH 39641 12 Amb a 1-U | Combined (Sum of) Rhinoconjunctivitis Daily Symptom Score (DSS) and Daily Medication Score (DMS) Averaged Over the Peak Ragweed Season (RS) | 6.22 score on a scale | Standard Error 0.543 |
| Placebo | Combined (Sum of) Rhinoconjunctivitis Daily Symptom Score (DSS) and Daily Medication Score (DMS) Averaged Over the Peak Ragweed Season (RS) | 8.46 score on a scale | Standard Error 0.521 |
p-value: 0.003995% CI: [-2.95, -0.57]ANOVA
p-value: 0.000295% CI: [-3.41, -1.07]ANOVA
Secondary
Average Combined Rhinoconjunctivitis DSS and DMS Over the Entire RS
The total combined score is a composite endpoint that combines the rhinoconjuntivitis DSS and the rhinoconjunctivitis DMS. The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18). Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medicationwith different rescue medications being assigned different scores/dose unit. The maximum rhinoconjunctivitis DMS score was 36. The sum of the rhinoconjunctivitis DSS and DMS could range from 0 to 54, with a lower score indicating less rhinoconjuntivitis symptoms and medication use. Raw means for DSS+DMS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.
Time frame: Approximately 5 weeks
Population: The FAS population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement. A total of 5 participants at one site were excluded from all efficacy analyses due to GCP issues.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCH 39641 6 Amb a 1-U | Average Combined Rhinoconjunctivitis DSS and DMS Over the Entire RS | 5.92 score on a scale | Standard Error 0.467 |
| SCH 39641 12 Amb a 1-U | Average Combined Rhinoconjunctivitis DSS and DMS Over the Entire RS | 5.21 score on a scale | Standard Error 0.45 |
| Placebo | Average Combined Rhinoconjunctivitis DSS and DMS Over the Entire RS | 7.01 score on a scale | Standard Error 0.434 |
p-value: 0.03295% CI: [-2.08, -0.09]ANOVA
p-value: 0.000395% CI: [-2.78, -0.82]ANOVA
Secondary
Average Rhinoconjunctivitis DMS for the Peak RS
Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medicationwith different rescue medications being assigned different scores/dose unit. The maximum rhinoconjunctivitis DMS score was 36, with a lower score indicating less rhinoconjuntivitis medication use. Raw means for DMS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.
Time frame: The 15-day period during the ragweed season with the highest moving pollen average
Population: The FAS population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement. A total of 5 participants at one site were excluded from all efficacy analyses due to GCP issues.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCH 39641 6 Amb a 1-U | Average Rhinoconjunctivitis DMS for the Peak RS | 1.89 score on a scale | Standard Error 0.314 |
| SCH 39641 12 Amb a 1-U | Average Rhinoconjunctivitis DMS for the Peak RS | 1.57 score on a scale | Standard Error 0.303 |
| Placebo | Average Rhinoconjunctivitis DMS for the Peak RS | 2.87 score on a scale | Standard Error 0.291 |
p-value: 0.003995% CI: [-1.65, -0.32]ANOVA
p-value: 0.000195% CI: [-1.95, -0.64]ANOVA
Secondary
Average Rhinoconjunctivitis DSS for the Entire RS
The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18), with a lower score indicating less rhinoconjuntivitis symptoms. Raw means for DSS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.
Time frame: Approximately 5 weeks
Population: The FAS population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement. A total of 5 participants at one site were excluded from all efficacy analyses due to GCP issues.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCH 39641 6 Amb a 1-U | Average Rhinoconjunctivitis DSS for the Entire RS | 4.41 score on a scale | Standard Error 0.306 |
| SCH 39641 12 Amb a 1-U | Average Rhinoconjunctivitis DSS for the Entire RS | 4.05 score on a scale | Standard Error 0.295 |
| Placebo | Average Rhinoconjunctivitis DSS for the Entire RS | 4.87 score on a scale | Standard Error 0.285 |
p-value: 0.168695% CI: [-1.11, 0.19]ANOVA
p-value: 0.012595% CI: [-1.46, -0.18]ANOVA
Secondary
Average Rhinoconjunctivitis DSS for the Peak RS
The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18), with a lower score indicating less rhinoconjuntivitis symptoms. Raw means for DSS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.
Time frame: The 15-day period during the ragweed season with the highest moving pollen average
Population: The FAS population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement. A total of 5 participants at one site were excluded from all efficacy analyses due to GCP issues.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCH 39641 6 Amb a 1-U | Average Rhinoconjunctivitis DSS for the Peak RS | 4.81 score on a scale | Standard Error 0.362 |
| SCH 39641 12 Amb a 1-U | Average Rhinoconjunctivitis DSS for the Peak RS | 4.65 score on a scale | Standard Error 0.349 |
| Placebo | Average Rhinoconjunctivitis DSS for the Peak RS | 5.59 score on a scale | Standard Error 0.335 |
p-value: 0.047295% CI: [-1.54, -0.01]ANOVA
p-value: 0.014495% CI: [-1.7, -0.19]ANOVA