Rhinitis, Allergic, Nonseasonal, Rhinitis, Allergic, Perennial
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of MK-8237 (SCH 900237) in the treatment of House Dust Mite (HDM)-Induced Allergic Rhinitis/Rhinoconjunctivitis (AR/ARC) in children and adults. The primary hypothesis of this study is that administration of MK-8237, compared to placebo, results in significant reduction in the average total combined rhinitis score (TCRS).
Interventions
BIOLOGICALMK-8237 tablets
MK-8237 12 DU rapidly dissolving tablets administered sublingually q.d.
BIOLOGICALPlacebo tablets
Placebo to MK-8237 rapidly dissolving tablets administered sublingually q.d.
DRUGRescue Medication: Self-Injectable Epinephrine
Self-injectable epinephrine (preferred dose of 0.30 mg) administered intramuscularly as needed for rescue medication.
DRUGRescue Medication: Loratadine tablets
Loratadine tablet 10 mg administered orally as needed for rescue medication.
DRUGRescue Medication: Olopatadine ophthalmic drops
Olopatadine hydrochloride ophthalmic drops 0.1% administered as needed for rescue medication.
DRUGRescue Medication: Mometasone furoate nasal spray
Mometasone furoate monohydrate nasal spray 50 mcg administered intranasally as needed for rescue medication.
Sponsors
Merck Sharp & Dohme LLC
ALK-Abelló A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of AR/ARC to house dust of 1 year duration or more (with or without asthma) * If female of childbearing potential, has a negative urine pregnancy test at Screening and agrees to remain abstinent or use (or have their partner use) an acceptable method of birth control within the projected duration of the study * Able to read, understand and complete questionnaires and diaries
Exclusion criteria
* Clinically relevant history of symptomatic ARC caused by animal dander, molds and/or cockroach (e.g. present in the home, job, daycare, etc.) or other perennial allergen * History of symptomatic seasonal ARC and/or asthma due to an allergen to which the participant is sensitized and regularly exposed * Nasal condition that could confound the efficacy or safety assessments (e.g., nasal polyposis) * Received an immunosuppressive treatment within 3 months prior to screening * Unstable or severe asthma, or has experienced a life-threatening asthma attack or an occurrence of any clinical deterioration of asthma that resulted in emergency treatment, hospitalization due to asthma, or treatment with systemic corticosteroids (but allowing short-acting beta agonists \[SABAs\]) at any time within 3 months prior to screening * Asthma requiring high-dose inhaled corticosteroids (ICS) within 6 months prior to screening * History of anaphylaxis with cardiorespiratory symptoms with prior immunotherapy, unknown cause or inhalant allergen * History of chronic urticaria and/or angioedema within 2 years prior to screening * History of chronic sinusitis during 2 years prior to screening * Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study * Previous immunotherapy treatment with any HDM allergen for more than 1 month within 5 years prior to screening * Previous exposure to MK-8237 * Receiving ongoing treatment with any specific immunotherapy at screening * Known history of allergy, hypersensitivity or intolerance to investigational medicinal products (except for D. pteronyssinus and/or D. farinae), rescue medications or self-injectable epinephrine * Unable to meet medication washout requirements prior to screening * Unable or unwilling to comply with the use of self-injectable epinephrine * Business or personal relationship with investigational site personnel or Sponsor who is directly involved with the conduct of the study * Likely to travel for extended periods of time during the efficacy assessment period * Participating in a different investigational study at any site during this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Total Combined Rhinitis Score (TCRS) During Last 8 Weeks of Treatment | Last 8 weeks of treatment (Weeks 44 to 52) | The TCRS is the sum of the rhinitis Daily Symptom Score (DSS; range: 0 to 12) and the rhinitis Daily Medication Score (DMS; range: 0 to 12); the total possible TCRS ranges from 0 to 24 points with higher scores indicative of greater symptom severity. The endpoint was calculated as the average daily diary entry score from the last 8 weeks of treatment. |
| Number of Participants Who Experience At Least One Adverse Event (AE) | Up to 54 weeks | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants Who Discontinue Study Drug Due to an AE | Up to 52 weeks | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Rhinitis Daily Symptom Score (Rhinitis DSS) During Last 8 Weeks of Treatment | Last 8 weeks of treatment (Weeks 44 to 52) | The Rhinitis DSS ranges from a score of 0 to 12 (higher scores indicative of greater symptom severity). The endpoint was calculated as the average daily diary entry score from the last 8 weeks of treatment. |
| Average Rhinitis Daily Medication Score (Rhinitis DMS) During Last 8 Weeks of Treatment | Last 8 weeks of treatment (Weeks 44 to 52) | The Rhinitis DMS ranges from a score of 0 to 12 (higher scores indicative of greater symptomatic medication use). The endpoint was calculated as the average daily diary entry score from the last 8 weeks of treatment. |
| Average Total Combined Rhinoconjunctivitis Score (TCS) During Last 8 Weeks of Treatment | Last 8 weeks of treatment (Weeks 44 to 52) | The TCS is the sum of the rhinoconjunctivitis DSS (rhinitis DSS and conjunctivitis DSS; range: 0 to 18) and the rhinoconjunctivitis DMS (rhinitis DMS and conjunctivitis DMS; range: 0 to 20); the total possible TCS ranges from 0 to 38 points with higher scores indicative of greater symptom severity. The endpoint was calculated as the average daily diary entry score from the last 8 weeks of treatment. |
| Average Allergic Rhinitis/Rhinoconjunctivitis Symptoms Assessed by Visual Analogue Scale (VAS) During Last 8 Weeks of Treatment | Last 8 weeks of treatment (Weeks 44 to 52) | Participants indicated the severity of symptoms in the past week on a VAS with a score range of 0 (no symptoms) to 100 (severe symptoms). Symptoms were assessed during 2 clinic visits occurring during the final 8 weeks of treatment (VAS score reflects the mean of 2 scores). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-8237 Participants took MK-8237 12 DU rapidly dissolving tablets administered sublingually q.d. for up to one year. | 741 |
| Placebo Participants took placebo to MK-8237 rapidly dissolving tablets administered sublingually q.d. for up to one year. | 741 |
| Total | 1,482 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 73 | 18 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 42 | 29 |
| Overall Study | Never received study drug | 1 | 0 |
| Overall Study | Noncompliance with study drug | 0 | 5 |
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Pregnancy | 1 | 4 |
| Overall Study | Progressive disease | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 4 |
| Overall Study | Technical problems | 0 | 1 |
| Overall Study | Withdrawal by Subject | 56 | 64 |
Baseline characteristics
| Characteristic | MK-8237 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34.9 Years STANDARD_DEVIATION 13.82 | 35.2 Years STANDARD_DEVIATION 13.74 | 35.1 Years STANDARD_DEVIATION 13.77 |
| Sex: Female, Male Female | 445 Participants | 430 Participants | 875 Participants |
| Sex: Female, Male Male | 296 Participants | 311 Participants | 607 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 642 / 743 | 389 / 738 |
| serious Total, serious adverse events | 11 / 743 | 7 / 738 |
Outcome results
Primary
Average Total Combined Rhinitis Score (TCRS) During Last 8 Weeks of Treatment
The TCRS is the sum of the rhinitis Daily Symptom Score (DSS; range: 0 to 12) and the rhinitis Daily Medication Score (DMS; range: 0 to 12); the total possible TCRS ranges from 0 to 24 points with higher scores indicative of greater symptom severity. The endpoint was calculated as the average daily diary entry score from the last 8 weeks of treatment.
Time frame: Last 8 weeks of treatment (Weeks 44 to 52)
Population: The analysis population consists of all randomized participants who received at least 1 dose of study drug and had data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8237 | Average Total Combined Rhinitis Score (TCRS) During Last 8 Weeks of Treatment | 4.67 Score on a Scale | Standard Deviation 3.55 |
| Placebo | Average Total Combined Rhinitis Score (TCRS) During Last 8 Weeks of Treatment | 5.49 Score on a Scale | Standard Deviation 3.82 |
p-value: <0.00195% CI: [-1.2, -0.4]Wilcoxon (Mann-Whitney)
95% CI: [-25, -9.7]
Primary
Number of Participants Who Discontinue Study Drug Due to an AE
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 52 weeks
Population: The APaT population consists of all randomized participants who received at least 1 dose of study drug (data presented according to actual treatment received).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-8237 | Number of Participants Who Discontinue Study Drug Due to an AE | 73 Participants |
| Placebo | Number of Participants Who Discontinue Study Drug Due to an AE | 19 Participants |
Primary
Number of Participants Who Experience At Least One Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 54 weeks
Population: The All Participants as Treated (APaT) population consists of all randomized participants who received at least 1 dose of study drug (data presented according to actual treatment received).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-8237 | Number of Participants Who Experience At Least One Adverse Event (AE) | 676 Participants |
| Placebo | Number of Participants Who Experience At Least One Adverse Event (AE) | 539 Participants |
Secondary
Average Allergic Rhinitis/Rhinoconjunctivitis Symptoms Assessed by Visual Analogue Scale (VAS) During Last 8 Weeks of Treatment
Participants indicated the severity of symptoms in the past week on a VAS with a score range of 0 (no symptoms) to 100 (severe symptoms). Symptoms were assessed during 2 clinic visits occurring during the final 8 weeks of treatment (VAS score reflects the mean of 2 scores).
Time frame: Last 8 weeks of treatment (Weeks 44 to 52)
Population: The analysis population consists of all randomized participants who received at least 1 dose of study drug and had data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8237 | Average Allergic Rhinitis/Rhinoconjunctivitis Symptoms Assessed by Visual Analogue Scale (VAS) During Last 8 Weeks of Treatment | 42.29 Score on a Scale | Standard Deviation 23.57 |
| Placebo | Average Allergic Rhinitis/Rhinoconjunctivitis Symptoms Assessed by Visual Analogue Scale (VAS) During Last 8 Weeks of Treatment | 47.96 Score on a Scale | Standard Deviation 23.66 |
p-value: <0.00195% CI: [-9.1, -3.1]Wilcoxon (Mann-Whitney)
95% CI: [-22.7, -8.3]
Secondary
Average Rhinitis Daily Medication Score (Rhinitis DMS) During Last 8 Weeks of Treatment
The Rhinitis DMS ranges from a score of 0 to 12 (higher scores indicative of greater symptomatic medication use). The endpoint was calculated as the average daily diary entry score from the last 8 weeks of treatment.
Time frame: Last 8 weeks of treatment (Weeks 44 to 52)
Population: The analysis population consists of all randomized participants who received at least 1 dose of study drug and had data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8237 | Average Rhinitis Daily Medication Score (Rhinitis DMS) During Last 8 Weeks of Treatment | 0.84 Score on a Scale | Standard Deviation 1.817 |
| Placebo | Average Rhinitis Daily Medication Score (Rhinitis DMS) During Last 8 Weeks of Treatment | 1.03 Score on a Scale | Standard Deviation 2.074 |
p-value: 0.15495% CI: [-0.35, 0.05]Zero-inflated Log-normal Model
95% CI: [-41, 4.3]
Secondary
Average Rhinitis Daily Symptom Score (Rhinitis DSS) During Last 8 Weeks of Treatment
The Rhinitis DSS ranges from a score of 0 to 12 (higher scores indicative of greater symptom severity). The endpoint was calculated as the average daily diary entry score from the last 8 weeks of treatment.
Time frame: Last 8 weeks of treatment (Weeks 44 to 52)
Population: The analysis population consists of all randomized participants who received at least 1 dose of study drug and had data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8237 | Average Rhinitis Daily Symptom Score (Rhinitis DSS) During Last 8 Weeks of Treatment | 3.83 Score on a Scale | Standard Deviation 2.64 |
| Placebo | Average Rhinitis Daily Symptom Score (Rhinitis DSS) During Last 8 Weeks of Treatment | 4.46 Score on a Scale | Standard Deviation 2.8 |
p-value: <0.00195% CI: [-1, -0.3]Wilcoxon (Mann-Whitney)
95% CI: [-24.4, -7.3]
Secondary
Average Total Combined Rhinoconjunctivitis Score (TCS) During Last 8 Weeks of Treatment
The TCS is the sum of the rhinoconjunctivitis DSS (rhinitis DSS and conjunctivitis DSS; range: 0 to 18) and the rhinoconjunctivitis DMS (rhinitis DMS and conjunctivitis DMS; range: 0 to 20); the total possible TCS ranges from 0 to 38 points with higher scores indicative of greater symptom severity. The endpoint was calculated as the average daily diary entry score from the last 8 weeks of treatment.
Time frame: Last 8 weeks of treatment (Weeks 44 to 52)
Population: The analysis population consists of all randomized participants who received at least 1 dose of study drug and had data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8237 | Average Total Combined Rhinoconjunctivitis Score (TCS) During Last 8 Weeks of Treatment | 6.40 Score on a Scale | Standard Deviation 5.16 |
| Placebo | Average Total Combined Rhinoconjunctivitis Score (TCS) During Last 8 Weeks of Treatment | 7.62 Score on a Scale | Standard Deviation 5.48 |
p-value: <0.00195% CI: [-1.7, -0.6]Wilcoxon (Mann-Whitney)
95% CI: [-24.6, -4]