Efficacy and Safety of Grass Sublingual Tablet in Children and Adolescents (P05239 AM3)(COMPLETED)

Phase 3

Completed

• Conditions: Rhinitis; Rhinoconjunctivitis; Conjunctivitis; Allergy
• Interventions: Biological: SCH 697243; Drug: Placebo; Drug: Loratadine Syrup 1 mg/mL Rescue Treatment; Drug: Loratadine 10 mg Rescue Treatment; Drug: Olopatadine 0.1% Rescue Treatment; Drug: Mometasone furoate 50 mcg Rescue Treatment; Drug: Albuterol 108 mcg Rescue Treatment; Drug: Fluticasone 44 mcg Rescue Treatment; Drug: Prednisone 5 mg Rescue Treatment

• Registration Number: NCT00550550
• Lead Sponsor: ALK-Abelló A/S

Brief Summary

The purpose of the study is to investigate the efficacy and safety of a grass sublingual tablet in children and adolescents with a history of grass-pollen induced rhinoconjunctivitis with or without asthma.

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in participants aged 5 to \<18 years of either sex, and of any race with a history of grass pollen induced rhinoconjunctivitis with or without asthma. While receiving treatment, participants will receive either grass sublingual tablet or placebo. Open-label rescue medications for the rhinoconjunctivitis and asthma symptoms will be provided. Participants will visit the study site for at least 12 visits. A total of 10 allergic symptoms, 6 rhinoconjunctivitis and 4 lung symptoms, will be recorded daily on an electronic diary by the participant/parent/guardian.

The start and end of the grass pollen season (GPS) was determined based on the regional grass pollen count, and lasted up to 162 days. For each region, the GPS is defined as the first day of 3 consecutive recorded days with a grass pollen count of ≥ 10 grains/m\^3, to the last day of the last occurrence of 3 consecutive recorded days with a grass pollen count ≥ 10 grains/m\^3, inclusively.

Study Timeline

• Study First Submitted: 2007-10-29
• Study First Submitted QC: 2007-10-29
• Study First Posted: 2007-10-30
• Study Start: 2007-11
• Primary Completion: 2009-09
• Study Completion: 2009-09
• Disposition First Submitted: 2009-10-22
• Disposition First Submitted QC: 2009-10-22
• Disposition First Posted: 2009-10-26
• Results First Submitted: 2012-08-07
• Results First Submitted QC: 2012-08-07
• Results First Posted: 2012-09-07
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-18
• Last Update Posted: 2017-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 345

Inclusion Criteria

• Participant must be 5 to <18 years of age, of either sex, and of any race.

• Participant must have a clinical history of significant allergic rhinoconjunctivitis to grass (with or without asthma) diagnosed by a physician and have received treatment for their disease during the previous GPS.

• Participant must have a positive skin prick test response (average wheal diameter >=5 mm larger than the saline control after 15 to 20 minutes) to Phleum pratense at the Screening Visit.

• Participant must have positive specific IgE against Phleum pratense (>= IgE Class 2) at the Screening Visit.

• Participant must have an FEV1 >=70% of predicted value at the Screening Visit.

• A participant's safety laboratory tests and vital signs conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor.

• A participant (and/or parent/guardian for subjects under the age of legal consent or who otherwise are unable to provide independent consent) must be willing to give written informed consent/assent and be able to adhere to dose and visit schedules.

• Female participants of childbearing potential must be using a medically acceptable and adequate form of birth control. These include:

  • hormonal contraceptives as prescribed by a physician (oral, hormonal vaginal ring, hormonal implant or depot injectable);
  • medically prescribed intra-uterine device;
  • medically prescribed topically-applied transdermal contraceptive patch;
  • double-barrier method (eg, condom in combination with a spermicide); vasectomy and tubal ligation should each be considered as single barrier.

• Female participants of childbearing potential should be counseled in the appropriate use of birth control while in the study. Female participants who are not currently sexually active must agree and consent to use one of the above-mentioned methods if they become sexually active while participating in the study.

• Female participants of childbearing potential must have a negative urine pregnancy test at the Screening Visit in order to be considered eligible for enrollment.

Exclusion Criteria

• Participant with a clinical history of symptomatic seasonal allergic rhinitis and/or asthma, having received regular medications due to another allergen during or potentially overlapping the GPS.
• Participant with a clinical history of significant symptomatic perennial allergic rhinitis and/or asthma having received regular medication due to an allergen to which the participant is regularly exposed.
• Participant with sufficient pre-seasonal data in the observational phase will not be eligible to continue in the treatment phase if the participant: 1) does not experience an increase in rhinoconjunctivitis symptom score of equal to or greater than 4 above the pre-seasonal average symptom score for at least 2 days, 2) does not use allergy rescue medication for at least 2 days, during the observational phase Year 1 2008 GPS.
• Participant has received an immunosuppressive treatment within 3 months prior to the Screening Visit (except steroids for allergic and asthma symptoms).
• Participant with a clinical history of severe asthma.
• Participant with history of anaphylaxis with cardiorespiratory symptoms.
• Participant with history of self-injectable epinephrine use.
• Participant with a history of chronic urticaria and angioedema.
• Participant with clinical history of chronic sinusitis during the 2 years prior to the Screening Visit.
• Participant with current severe atopic dermatitis.
• Female participants who are breast-feeding, pregnant, or intending to become pregnant.
• Participant who has had previous treatment by immunotherapy with grass pollen allergen or any other allergen within the 5 years prior to the Screening Visit.
• Participant with a known history of allergy, hypersensitivity or intolerance to the ingredients of the IMP (except for Phleum pratense), rescue medications, or self-injectable epinephrine.
• Participant with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study. Specific examples include but are not limited to hypertension being treated with beta blockers, coronary artery disease, arrhythmia, stroke, ocular conditions requiring topical beta blockers, any condition requiring the use of beta blockers.
• Participant who has used any investigational drugs within 30 days of the Screening Visit.
• Participant who is participating in any other clinical study.
• Participant who is a family member of the investigational study staff conducting this study.
• Participant who is unable to meet medication washout requirements as listed in the protocol.
• Participant who is unlikely to be able to complete the trial, for any reason, or likely to travel for extended periods of time during the GPS, which in the opinion of the investigator will compromise the data.
• Participant with a clinically significant abnormal vital sign or laboratory value that would preclude participation in the study.
• A participant participating in this study may not participate in this same study at another investigational site.
• A participant must not be randomized into this study more than once.
• Participant who is unable to or will not comply with the use of self-injectable epinephrine.
• Participants who may be at greater risk of developing adverse reactions after epinephrine administration.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Olopatadine 0.1% Rescue Treatment	Matching Placebo
SCH 697243	Olopatadine 0.1% Rescue Treatment	Grass Sublingual Tablet (Phleum pratense extract)
Placebo	Albuterol 108 mcg Rescue Treatment	Matching Placebo
Placebo	Fluticasone 44 mcg Rescue Treatment	Matching Placebo
Placebo	Mometasone furoate 50 mcg Rescue Treatment	Matching Placebo
Placebo	Prednisone 5 mg Rescue Treatment	Matching Placebo
Placebo	Loratadine 10 mg Rescue Treatment	Matching Placebo
SCH 697243	Loratadine 10 mg Rescue Treatment	Grass Sublingual Tablet (Phleum pratense extract)
SCH 697243	Albuterol 108 mcg Rescue Treatment	Grass Sublingual Tablet (Phleum pratense extract)
SCH 697243	Fluticasone 44 mcg Rescue Treatment	Grass Sublingual Tablet (Phleum pratense extract)
SCH 697243	SCH 697243	Grass Sublingual Tablet (Phleum pratense extract)
SCH 697243	Mometasone furoate 50 mcg Rescue Treatment	Grass Sublingual Tablet (Phleum pratense extract)
Placebo	Placebo	Matching Placebo
Placebo	Loratadine Syrup 1 mg/mL Rescue Treatment	Matching Placebo
SCH 697243	Loratadine Syrup 1 mg/mL Rescue Treatment	Grass Sublingual Tablet (Phleum pratense extract)
SCH 697243	Prednisone 5 mg Rescue Treatment	Grass Sublingual Tablet (Phleum pratense extract)

Primary Outcome Measures

Name	Time	Method
Participant Total Combined Symptom (TCS) Score Over the Entire Grass Pollen Season (GPS)	From the Start of the GPS to the End of the GPS	The TCS is the sum of the rhinoconjunctivitis daily symptom score (DSS) and rhinoconjunctivitis daily medication score (DMS) averaged over the entire GPS. The TCS ranged from 0 (no symptoms and no rescue medication use) to 54 (most severe symptoms and maximum use of rescue medication), with increasing score indicating a higher level of symptom severity. The DSS is composed of 6 rhinoconjunctivitis symptoms with scores from 0 (best) to 18 (worst), with increasing score indicating increased severity. The DMS is composed of a sum of the scores associated with rescue medication use per day. The range for the DMS was 0 (no rescue medication use) to 36 (maximum use of rescue medication), with a lower score indicating less use of rescue medication.

Secondary Outcome Measures

Name	Time	Method
Participant Average Rhinoconjunctivitis Daily Symptom Scores (DSS) Over the Entire GPS	Start of the GPS to the End of the GPS	The DSS is composed of six rhinoconjunctivitis symptoms which were recorded daily including runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy, and watery eyes, and the symptoms were measured on a scale of 0 (no symptom) to 3 (severe symptoms). A higher score indicated a higher level of symptoms and the total daily score could range from 0 (best) to 18 (worst).
Participant Average Rhinoconjunctivitis Daily Medication Score (DMS) Over the Entire GPS	Start of the GPS to the End of the GPS	The DMS is composed of a sum of the scores associated with rescue medication use per day. Rescue medications were implemented when a participant had a symptom score \>= 4. Rescue medications for allergic rhinoconjunctivitis were to be utilized in a step-wise fashion: loratadine, olopatadine hydrochloride 0.1% opthalmic solution, mometasone, and prednisone, in that sequence. The score for the DMS ranged from 0 (no use of rescue medication) to 36 (maximum use of rescue medication). A lower medication score indicated less impact on symptoms and was suggestive of less use of rescue medication.
Participant Average Weekly Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) Total Score Over the Entire GPS	Start of the GPS to the End of the GPS	The RQLQ has 28 questions and focusses on 7 domains that may be significantly impaired in participants with seasonal allergic rhinoconjunctivitis: sleep impairment, non-nasal symptoms, practical problems, nasal symptoms, eye symptoms, activity limitations, and emotional difficulty. The RQLQ score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. RQLQ scores range from 0 (best) to 6 (worst), with a higher score indicating more significant impairment.