Allergy
Conditions
Keywords
Immunology
Brief summary
This study assessed the safety profile of short ragweed (Ambrosia artemisiifolia) in participants with ragweed-induced rhinoconjunctivitis with or without asthma. The primary objective was to compare treatment-emergent adverse events (AEs) for participants treated with short ragweed allergy immunotherapy tablet (AIT) with those treated with placebo.
Interventions
BIOLOGICALSCH 39641
Rapidly dissolving tablet sublingually once daily
DRUGPlacebo for SCH 39641
Rapidly dissolving tablet sublingually 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 No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical history of physician-diagnosed ragweed-induced allergic rhinoconjunctivitis of 2 years duration or more, with or without asthma * Must have a positive skin prick test response to Ambrosia artemisiifolia * Must have a forced expiratory volume in 1 second (FEV1) of at least 70% of predicted value * Clinical laboratory tests, electrocardiogram (ECG) and vital signs conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor * Females of child-bearing potential must agree to use medically accepted methods of contraception
Exclusion criteria
* Unstable asthma or has experienced an occurrence of any clinical deterioration of asthma that resulted in emergency treatment, hospitalization due to asthma, or treatment with systemic corticosteroids in previous 3 months * Received an immunosuppressive treatment within 3 months * History of anaphylaxis with cardio-respiratory symptoms. * History of chronic urticaria or angioedema * Current severe atopic dermatitis * Female subject who is breastfeeding, pregnant, or intending to become pregnant * Has received maintenance doses of immunotherapy with ragweed extract for ≥1 month within the last 5 years * History of allergy, hypersensitivity or intolerance to the ingredients of the investigational medicinal products (IMPs) (except for Ambrosia artemisiifolia), or self-injectable epinephrine * Unable to or will not comply with the use of self-injectable epinephrine * Participating in any other clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (AEs) | Up to Day 35 | Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with treatment-emergent AEs were recorded. An AE is any unfavorable and unintended sign, symptom or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent AEs are new AEs that occur after participants have been randomized into the trial, or existing AEs that occurred during Screening that increase in severity after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Ear Pruritus | Up to Day 35 | Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with ear pruritus were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported. |
| Number of Participants Reporting Throat Irritation | Up to Day 35 | Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with throat irritation were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported. |
| Number of Participants Reporting Mouth Oedema | Up to Day 35 | Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with mouth oedema were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported. |
| Number of Participants Reporting Oral Pruritus. | Up to Day 35 | Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with oral pruritus were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported. |
| Number of Participants Reporting Nasal Passage Irritation | Up to Day 35 | Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with nasal passage irritation were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported. |
| Number of Participants Reporting Skin Pruritus | Up to Day 35 | Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with skin pruritus were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported. |
| Number of Participants Who Discontinued Due to Treatment-emergent AEs | Up to Day 28 | Participants were treated with either SCH 39641 12 Amb a 1-U or placebo for 28 days, and the number who discontinued due to treatment emergent-AEs were recorded. An AE is any unfavorable and unintended sign, symptom or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent AEs are new AEs that occur after participants have been randomized into the trial, or existing AEs that occurred during Screening that increase in severity after randomization. |
| Number of Participants Reporting Eye Pruritus | Up to Day 35 | Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with eye pruritus were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SCH 39641 12 Amb a 1-U 12 Amb a 1-U extract in an AIT, sublingual, once daily. | 610 |
| Placebo Matching placebo tablet, sublingual, once daily. | 304 |
| Total | 914 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 21 | 3 |
| Overall Study | Did not meet Protocol Eligibility | 3 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Protocol Violation | 4 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | SCH 39641 12 Amb a 1-U | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 40.7 Years STANDARD_DEVIATION 12.6 | 42.3 Years STANDARD_DEVIATION 12.2 | 41.2 Years STANDARD_DEVIATION 12.5 |
| Gender Female | 345 Participants | 177 Participants | 522 Participants |
| Gender Male | 265 Participants | 127 Participants | 392 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 199 / 609 | 57 / 304 |
| serious Total, serious adverse events | 1 / 609 | 3 / 304 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (AEs)
Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with treatment-emergent AEs were recorded. An AE is any unfavorable and unintended sign, symptom or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent AEs are new AEs that occur after participants have been randomized into the trial, or existing AEs that occurred during Screening that increase in severity after randomization.
Time frame: Up to Day 35
Population: All subjects as treated (ASAT) consisting of participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCH 39641 12 Amb a 1-U | Number of Participants With Treatment-emergent Adverse Events (AEs) | 321 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs) | 130 Participants |
p-value: 0.00595% CI: [3.1, 16.7]Stratified Miettinen and Nurminen
Secondary
Number of Participants Reporting Ear Pruritus
Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with ear pruritus were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported.
Time frame: Up to Day 35
Population: ASAT consisting of participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCH 39641 12 Amb a 1-U | Number of Participants Reporting Ear Pruritus | 52 Participants |
| Placebo | Number of Participants Reporting Ear Pruritus | 2 Participants |
p-value: <0.00195% CI: [5.5, 10.5]Stratified Miettinen and Nurminen
Secondary
Number of Participants Reporting Eye Pruritus
Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with eye pruritus were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported.
Time frame: Up to Day 35
Population: ASAT consisting of participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCH 39641 12 Amb a 1-U | Number of Participants Reporting Eye Pruritus | 11 Participants |
| Placebo | Number of Participants Reporting Eye Pruritus | 5 Participants |
p-value: 0.86195% CI: [-2.1, 1.9]Stratified Miettinen and Nurminen
Secondary
Number of Participants Reporting Mouth Oedema
Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with mouth oedema were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported.
Time frame: Up to Day 35
Population: ASAT consisting of participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCH 39641 12 Amb a 1-U | Number of Participants Reporting Mouth Oedema | 34 Participants |
| Placebo | Number of Participants Reporting Mouth Oedema | 1 Participants |
p-value: <0.00195% CI: [3.3, 7.4]Stratified Miettinen and Nurminen
Secondary
Number of Participants Reporting Nasal Passage Irritation
Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with nasal passage irritation were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported.
Time frame: Up to Day 35
Population: ASAT consisting of participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCH 39641 12 Amb a 1-U | Number of Participants Reporting Nasal Passage Irritation | 21 Participants |
| Placebo | Number of Participants Reporting Nasal Passage Irritation | 7 Participants |
p-value: 0.34495% CI: [-1.5, 3.3]Stratified Miettinen and Nurminen
Secondary
Number of Participants Reporting Oral Pruritus.
Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with oral pruritus were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported.
Time frame: Up to Day 35
Population: ASAT consisting of participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCH 39641 12 Amb a 1-U | Number of Participants Reporting Oral Pruritus. | 44 Participants |
| Placebo | Number of Participants Reporting Oral Pruritus. | 5 Participants |
p-value: <0.00195% CI: [2.9, 8.2]Stratified Miettinen and Nurminen
Secondary
Number of Participants Reporting Skin Pruritus
Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with skin pruritus were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported.
Time frame: Up to Day 35
Population: ASAT consisting of participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCH 39641 12 Amb a 1-U | Number of Participants Reporting Skin Pruritus | 18 Participants |
| Placebo | Number of Participants Reporting Skin Pruritus | 6 Participants |
p-value: 0.38295% CI: [-1.5, 3]Stratified Miettinen and Nurminen
Secondary
Number of Participants Reporting Throat Irritation
Participants were treated for 28 days with either SCH 39641 12 Amb a 1-U or placebo, and the number with throat irritation were recorded. All AEs, combining non-treatment-emergent AEs with treatment-emergent AEs, were reported.
Time frame: Up to Day 35
Population: ASAT consisting of participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCH 39641 12 Amb a 1-U | Number of Participants Reporting Throat Irritation | 82 Participants |
| Placebo | Number of Participants Reporting Throat Irritation | 10 Participants |
p-value: <0.00195% CI: [6.6, 13.6]Stratified Miettinen and Nurminen
Secondary
Number of Participants Who Discontinued Due to Treatment-emergent AEs
Participants were treated with either SCH 39641 12 Amb a 1-U or placebo for 28 days, and the number who discontinued due to treatment emergent-AEs were recorded. An AE is any unfavorable and unintended sign, symptom or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent AEs are new AEs that occur after participants have been randomized into the trial, or existing AEs that occurred during Screening that increase in severity after randomization.
Time frame: Up to Day 28
Population: ASAT consisting of participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCH 39641 12 Amb a 1-U | Number of Participants Who Discontinued Due to Treatment-emergent AEs | 21 Participants |
| Placebo | Number of Participants Who Discontinued Due to Treatment-emergent AEs | 3 Participants |
p-value: 0.02995% CI: [0.3, 4.4]Stratified Miettinen and Nurminen