Rhinitis, Allergic, Seasonal
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of MK-3641 (short ragweed \[Ambrosia artemisiifolia\] extract, SCH 039641, RAGWITEK®) sublingual tablets and MK-7243 (Timothy grass \[Phleum pratense\] extract, SCH 697243, GRASTEK®) sublingual tablets co-administered in participants 18 through 65 years of age with both ragweed- and grass polled-induced allergic rhinitis, with or without conjunctivitis and with or without asthma. The primary endpoint is the percentage of participants who experience at least one event of local swelling after co-administration of MK-3641 and MK-7243 sublingual tablets.
Detailed description
Events of local swelling include pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema or throat tightness.
Interventions
BIOLOGICALMK-3641 12 Amb a 1-U (short ragweed extract)
12 units of Ambrosia artemisiifolia major allergen number 1 (Amb a 1-U) extract sublingual tablets
BIOLOGICALMK-7243 2800 BAU (Timothy grass extract)
2800 bioequivalent allergen units (BAU) of Phleum pratense extract sublingual tablets
DRUGRescue Medication
Self-injectable epinephrine, to be administered for an anaphylactic reaction, including symptoms/signs of upper airway obstruction.
Sponsors
ALK-Abelló A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Clinical history of physician-diagnosed ragweed- and grass pollen-induced rhinitis with or without conjunctivitis of \>1 year duration, with or without asthma * Female participants of childbearing potential must have a negative urine pregnancy test at Screening and Randomization Visits and must agree to remain abstinent or use (or have their partner use) any one of the acceptable methods of birth control within the projected duration of the study. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy, hormonal contraception.
Exclusion criteria
* Unstable, uncontrolled or severe asthma treated with long-acting beta agonists (LABAs) at the time of Screening * Received immunosuppressive treatment within 3 months prior to Randomization (except steroids for allergic reactions other than asthma) * History of anaphylaxis with cardiorespiratory symptoms with prior immunotherapy, unknown cause, or inhalant allergen * Diagnosis of eosinophilic esophagitis * History of any severe systemic allergic reaction or any severe local reaction to sublingual allergen immunotherapy * Female and breastfeeding, pregnant or intending to become pregnant * Received another form of allergen immunotherapy with the past month * Previously exposed to MK-3641 (RAGWITEK®) or other sublingual ragweed immunotherapy * Previously exposed to MK-7243 (GRASTEK®) or other sublingual grass immunotherapy * Known history of allergy, hypersensitivity, or intolerance to the excipient ingredients of the study drug (except for Ambrosia artemisiifolia and/or Phleum pratense), or self-injectable epinephrine * Unable to or will not comply with the use of self-injectable epinephrine * Used an investigational drug within 30 days prior to Screening Visit, or plans to participate in another interventional clinical trial during the duration of this trial * Family member of the investigational or sponsor staff involved in this trial * Participating in this same trial at another investigational site.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced at Least One Event of Local Swelling | During Period I, Period II and Period III (Up to 6 weeks) | Events of local swelling included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, or throat tightness. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the World Allergy Organization (WAO) as local side effects of sublingual immunotherapy (SLIT) that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction | During Period I, Period II and Period III (Up to 6 weeks) | Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered. |
| Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | During Period I, Period II and Period III (Up to 6 weeks) | An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study drug, was also an AE. |
| Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment | During Period I, Period II and Period III (Up to 6 weeks) | Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-3641+MK-7243 Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III. | 102 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period I | Adverse Event | 5 |
| Period I | Protocol Violation | 1 |
| Period II | Adverse Event | 1 |
| Period II | Subject Moved | 1 |
| Period III | Adverse Event | 3 |
Baseline characteristics
| Characteristic | MK-3641+MK-7243 |
|---|---|
| Age, Continuous | 40.0 Years STANDARD_DEVIATION 12 |
| Gender Female | 53 Participants |
| Gender Male | 49 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 | 74 / 102 | 68 / 96 | 55 / 94 |
| serious Total, serious adverse events | 0 / 102 | 1 / 96 | 0 / 94 |
Outcome results
Primary
Percentage of Participants Who Experienced at Least One Event of Local Swelling
Events of local swelling included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, or throat tightness. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the World Allergy Organization (WAO) as local side effects of sublingual immunotherapy (SLIT) that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.
Time frame: During Period I, Period II and Period III (Up to 6 weeks)
Population: All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-3641+MK-7243 | Percentage of Participants Who Experienced at Least One Event of Local Swelling | Period I | 13.7 Percentage of Participants |
| MK-3641+MK-7243 | Percentage of Participants Who Experienced at Least One Event of Local Swelling | Period II | 21.6 Percentage of Participants |
| MK-3641+MK-7243 | Percentage of Participants Who Experienced at Least One Event of Local Swelling | Period III | 14.7 Percentage of Participants |
Secondary
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study drug, was also an AE.
Time frame: During Period I, Period II and Period III (Up to 6 weeks)
Population: All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-3641+MK-7243 | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | Period I | 4.9 Percentage of Participants |
| MK-3641+MK-7243 | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | Period II | 1.0 Percentage of Participants |
| MK-3641+MK-7243 | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | Period III | 2.9 Percentage of Participants |
Secondary
Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction
Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.
Time frame: During Period I, Period II and Period III (Up to 6 weeks)
Population: All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-3641+MK-7243 | Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction | Period I | 70.6 Percentage of Participants |
| MK-3641+MK-7243 | Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction | Period II | 68.6 Percentage of Participants |
| MK-3641+MK-7243 | Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction | Period III | 55.9 Percentage of Participants |
Secondary
Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment
Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.
Time frame: During Period I, Period II and Period III (Up to 6 weeks)
Population: All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-3641+MK-7243 | Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment | Period I | 4.9 Percentage of Participants |
| MK-3641+MK-7243 | Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment | Period II | 3.9 Percentage of Participants |
| MK-3641+MK-7243 | Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment | Period III | 1.0 Percentage of Participants |