Safety Study of Ragweed Allergy Immunotherapy Tablet in Subjects 50 Years of Age and Older (Study P06081)
Study Details
Study Description
Brief Summary
The purpose of this study was to assess the safety and tolerability of a ragweed allergy immunotherapy tablet (AIT) administered sublingually (under-the tongue) in subjects 50 years of age and older with ragweed-induced rhinoconjunctivitis, with or without asthma.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Placebo Comparator: Placebo Matching placebo tablet sublingual, once daily |
Drug: Placebo
Placebo sublingual tablet, once daily
|
Experimental: SCH 39641 6 Amb a 1-U 6 Units Short Ragweed (Ambrosia artemisiifolia) Major Allergen 1 (Amb a 1-U) in an AIT, sublingual, once daily |
Biological: SCH 39641
Allergy immunotherapy tablet (sublingual)
Other Names:
|
Experimental: SCH 39641 12 Amb a 1-U 12 Amb a 1-U in an AIT, sublingual, once daily |
Biological: SCH 39641
Allergy immunotherapy tablet (sublingual)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The Proportion of Participants Reporting Treatment-emergent Adverse Events (AEs) [Up to Day 42]
Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion 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 Outcome Measures
- Proportion of Participants Reporting Oral Pruritus [Up to Day 42]
Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with oral pruritus were reported.
- Proportion of Participants Reporting Ear Pruritus [Up to Day 42]
Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with ear pruritus were reported.
- Proportion of Participants Reporting Throat Irritation [Up to Day 42]
Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with throat irritation were reported.
- Proportion of Participants Reporting Mouth Oedema [Up to Day 42]
Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with mouth oedema were reported.
- Proportion of Participants Who Discontinued Due to Adverse Events. [Up to Day 28]
Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with AEs leading to study discontinuation were reported. 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subject must be 50 years of age or older, of either sex, and of any race/ethnicity.
-
Subject must have a clinical history of ragweed-induced allergic rhinoconjunctivitis with or without asthma.
-
Subject must have a positive skin prick test response to Ambrosia artemisiifolia at the Screening Visit
-
Subject must have a forced expiratory volume in 1 second (FEV1) of at least 70% of predicted value at the Screening Visit and at Randomization.
-
A subject's clinical laboratory tests, electrocardiogram (ECG) and vital signs conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator.
Exclusion Criteria:
-
Subject with asthma who requires inhaled corticosteroids for the treatment of their asthma during the study period.
-
Subject requiring anti-allergy medications during the time period from randomization to study completion.
-
Subject who has received an immunosuppressive treatment within 3 months prior to the Screening Visit (except steroids for allergic and asthma symptoms).
-
Subject with a history of anaphylaxis with cardiorespiratory symptoms.
-
Subject with a history of chronic urticaria or angioedema.
-
Subject with current severe atopic dermatitis.
-
Female subject who is breastfeeding, pregnant, or intending to become pregnant.
-
Subject with a history of allergy, hypersensitivity or intolerance to the ingredients of the investigational medicinal products (IMPs) (except for Ambrosia artemisiifolia), or self-injectable epinephrine.
-
Subject with a history of self-injectable epinephrine use.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- ALK-Abelló A/S
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P06081
- MK-3641-004
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Due to non-compliance with Good Clinical Practice (GCP) 7 randomized participants who completed treatment were excluded from all subsequent analysis. |
Arm/Group Title | Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U |
---|---|---|---|
Arm/Group Description | Matching placebo tablet sublingual, once daily | 6 Units Short Ragweed (Ambrosia artemisiifolia) Major Allergen 1 (Amb a 1-U) in an Allergy Immunotherapy Tablet (AIT) sublingual, once daily | 12 Amb a 1-U in an AIT, sublingual, once daily |
Period Title: Overall Study | |||
STARTED | 65 | 66 | 65 |
COMPLETED | 64 | 63 | 59 |
NOT COMPLETED | 1 | 3 | 6 |
Baseline Characteristics
Arm/Group Title | Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Total |
---|---|---|---|---|
Arm/Group Description | Matching placebo tablet sublingual, once daily | 6 Amb a 1-U in an AIT, sublingual, once daily | 12 Amb a 1-U in an AIT, sublingual, once daily | Total of all reporting groups |
Overall Participants | 65 | 66 | 65 | 196 |
Age (Years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [Years] |
56.4
(4.7)
|
56.4
(5.4)
|
56.2
(5.7)
|
56.3
(5.3)
|
Gender (Count of Participants) | ||||
Female |
38
58.5%
|
43
65.2%
|
40
61.5%
|
121
61.7%
|
Male |
27
41.5%
|
23
34.8%
|
25
38.5%
|
75
38.3%
|
Outcome Measures
Title | The Proportion of Participants Reporting Treatment-emergent Adverse Events (AEs) |
---|---|
Description | Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion 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 42 |
Outcome Measure Data
Analysis Population Description |
---|
All subjects as treated (ASAT) consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis. |
Arm/Group Title | Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U |
---|---|---|---|
Arm/Group Description | Matching placebo tablet sublingual, once daily | 6 Amb a 1-U in an AIT, sublingual, once daily | 12 Amb a 1-U in an AIT, sublingual, once daily |
Measure Participants | 65 | 66 | 65 |
Number [Proportion of Participants] |
0.446
0.7%
|
0.515
0.8%
|
0.615
0.9%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, SCH 39641 6 Amb a 1-U |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.486 |
Comments | ||
Method | Fisher Exact | |
Comments | ||
Method of Estimation | Estimation Parameter | Percent Difference |
Estimated Value | 6.9 | |
Confidence Interval |
(2-Sided) 95% -10.17 to 23.97 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, SCH 39641 12 Amb a 1-U |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.078 |
Comments | ||
Method | Fisher Exact | |
Comments | ||
Method of Estimation | Estimation Parameter | Percent Difference |
Estimated Value | 16.9 | |
Confidence Interval |
(2-Sided) 95% 0.01 to 33.83 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Proportion of Participants Reporting Oral Pruritus |
---|---|
Description | Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with oral pruritus were reported. |
Time Frame | Up to Day 42 |
Outcome Measure Data
Analysis Population Description |
---|
ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis. |
Arm/Group Title | Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U |
---|---|---|---|
Arm/Group Description | Matching placebo tablet sublingual, once daily | 6 Amb a 1-U in an AIT, sublingual, once daily | 12 Amb a 1-U in an AIT, sublingual, once daily |
Measure Participants | 65 | 66 | 65 |
Number [Proportion of Participants] |
0.015
0%
|
0.167
0.3%
|
0.169
0.3%
|
Title | Proportion of Participants Reporting Ear Pruritus |
---|---|
Description | Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with ear pruritus were reported. |
Time Frame | Up to Day 42 |
Outcome Measure Data
Analysis Population Description |
---|
ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis. |
Arm/Group Title | Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U |
---|---|---|---|
Arm/Group Description | Matching placebo tablet sublingual, once daily | 6 Amb a 1-U in an AIT, sublingual, once daily | 12 Amb a 1-U in an AIT, sublingual, once daily |
Measure Participants | 65 | 66 | 65 |
Number [Proportion of Participants] |
0
0%
|
0.061
0.1%
|
0.077
0.1%
|
Title | Proportion of Participants Reporting Throat Irritation |
---|---|
Description | Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with throat irritation were reported. |
Time Frame | Up to Day 42 |
Outcome Measure Data
Analysis Population Description |
---|
ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis. |
Arm/Group Title | Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U |
---|---|---|---|
Arm/Group Description | Matching placebo tablet sublingual, once daily | 6 Amb a 1-U in an AIT, sublingual, once daily | 12 Amb a 1-U in an AIT, sublingual, once daily |
Measure Participants | 65 | 66 | 65 |
Number [Proportion of Participants] |
0.015
0%
|
0.121
0.2%
|
0.077
0.1%
|
Title | Proportion of Participants Reporting Mouth Oedema |
---|---|
Description | Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with mouth oedema were reported. |
Time Frame | Up to Day 42 |
Outcome Measure Data
Analysis Population Description |
---|
ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis. |
Arm/Group Title | Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U |
---|---|---|---|
Arm/Group Description | Matching placebo tablet sublingual, once daily | 6 Amb a 1-U in an AIT, sublingual, once daily | 12 Amb a 1-U in an AIT, sublingual, once daily |
Measure Participants | 65 | 66 | 65 |
Number [Proportion of Participants] |
0
0%
|
0.015
0%
|
0
0%
|
Title | Proportion of Participants Who Discontinued Due to Adverse Events. |
---|---|
Description | Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with AEs leading to study discontinuation were reported. 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. |
Time Frame | Up to Day 28 |
Outcome Measure Data
Analysis Population Description |
---|
ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis. |
Arm/Group Title | Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U |
---|---|---|---|
Arm/Group Description | Matching placebo tablet sublingual, once daily | 6 Amb a 1-U in an AIT, sublingual, once daily | 12 Amb a 1-U in an AIT, sublingual, once daily |
Measure Participants | 65 | 66 | 65 |
Number [Proportion of Participants] |
0.015
0%
|
0.03
0%
|
0.077
0.1%
|
Adverse Events
Time Frame | Up to Day 42 | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis. | |||||
Arm/Group Title | Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | |||
Arm/Group Description | Matching placebo tablet sublingual, once daily | 6 Amb a 1-U in an AIT, sublingual, once daily | 12 Amb a 1-U in an AIT, sublingual, once daily | |||
All Cause Mortality |
||||||
Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/65 (0%) | 0/66 (0%) | 1/65 (1.5%) | |||
Hepatobiliary disorders | ||||||
Cholecystitis acute | 0/65 (0%) | 0 | 0/66 (0%) | 0 | 1/65 (1.5%) | 1 |
Injury, poisoning and procedural complications | ||||||
Post procedural bile leak | 0/65 (0%) | 0 | 0/66 (0%) | 0 | 1/65 (1.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
Placebo | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 11/65 (16.9%) | 23/66 (34.8%) | 23/65 (35.4%) | |||
Ear and labyrinth disorders | ||||||
Ear pruritus | 0/65 (0%) | 0 | 4/66 (6.1%) | 5 | 5/65 (7.7%) | 5 |
Eye disorders | ||||||
Eye pruritus | 4/65 (6.2%) | 4 | 2/66 (3%) | 2 | 4/65 (6.2%) | 4 |
Gastrointestinal disorders | ||||||
Dry mouth | 2/65 (3.1%) | 2 | 1/66 (1.5%) | 1 | 4/65 (6.2%) | 6 |
Hypoaesthesia oral | 0/65 (0%) | 0 | 1/66 (1.5%) | 1 | 4/65 (6.2%) | 5 |
Oral pruritus | 1/65 (1.5%) | 1 | 11/66 (16.7%) | 15 | 11/65 (16.9%) | 21 |
Paraesthesia oral | 3/65 (4.6%) | 3 | 3/66 (4.5%) | 3 | 4/65 (6.2%) | 4 |
Respiratory, thoracic and mediastinal disorders | ||||||
Nasal congestion | 1/65 (1.5%) | 1 | 4/66 (6.1%) | 5 | 2/65 (3.1%) | 2 |
Throat irritation | 2/65 (3.1%) | 2 | 8/66 (12.1%) | 11 | 6/65 (9.2%) | 7 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The investigator agrees to provide to the sponsor for review 45 days prior to submission for publication or presentation, copies of abstracts or manuscripts for publication that report any results of the trial. If the parties disagree concerning the sponsor's confidential information, the investigator agrees to meet with the sponsor's representative, prior to submission for publication, in order to make good faith efforts to discuss and resolve any issues or disagreements.
Results Point of Contact
Name/Title | Senior Vice President, Global Clinical Development |
---|---|
Organization | Merck Sharp & Dohme Corp. |
Phone | |
ClinicalTrialsDisclosure@merck.com |
- P06081
- MK-3641-004