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

NCT ID: NCT00550550

Last Updated: 2017-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 345 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2009-09-30

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.

Conditions

Rhinoconjunctivitis; Rhinitis; Conjunctivitis; Allergy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Matching Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo sublingual tablet, once daily

Loratadine Syrup 1 mg/mL Rescue Treatment

Intervention Type: DRUG

Loratadine Syrup 1 mg/mL was dosed orally once daily at a dose of 5 mg for children aged 5 to \<6 years of age and at a dose of 10 mg for children aged 6 to \<18 years of age as rescue medication for symptoms of rhinoconjunctivitis among participants with a total symptom score ≥4.

Loratadine 10 mg Rescue Treatment

Intervention Type: DRUG

Loratadine 10 mg RediTabs tablets were dosed orally once daily at a dose of 10 mg for children aged 6 to \<18 years of age as rescue medication for symptoms of rhinoconjunctivitis among participants with a total symptom score ≥4.

Olopatadine 0.1% Rescue Treatment

Intervention Type: DRUG

Olopatadine hydrochloride 0.1% ophthalmic solution was dosed intraocularly at a dose of 1 drop in each affected eye twice daily, in addition to loratadine, as rescue medication for participants with persistent eye symptoms due to rhinoconjunctivitis.

Mometasone furoate 50 mcg Rescue Treatment

Intervention Type: DRUG

Mometasone furoate monohydrate nasal spray 50 mcg was dosed intranasally at a dose of one spray in each nostril once daily for participants aged 5 to \<12 years and a dose of 2 sprays in each nostril once daily for participants aged 12 to \<18 years as rescue medication for nasal symptoms of rhinoconjunctivitis among participants with a total symptom score of ≥4 despite loratadine and mometasone furoate nasal spray.

Albuterol 108 mcg Rescue Treatment

Intervention Type: DRUG

Albuterol sulfate inhalation aerosol 108 mcg/inhalation was administered via inhalation at a dose of 2 inhalations every 4 to 6 hours as rescue medication among participants aged 5 to \<18 years with asthma symptoms .

Fluticasone 44 mcg Rescue Treatment

Intervention Type: DRUG

Fluticasone propionate inhalation aerosol 44 mcg/inhalation was administered via inhalation at a dose of 2 inhalations twice daily among participants aged 12 to \<18 years up to a maximum dose of 10 inhalations twice daily, in combination with albuterol, among participants with ≥4 albuterol sulfate inhalations/day for 2 days as rescue medication for nocturnal asthma or shortness of breath.

Prednisone 5 mg Rescue Treatment

Intervention Type: DRUG

Prednisone tablet 5 mg was administered orally at a dose of 1 mg/kg/day once daily up to a maximum of 50 mg/day on Day 1, and at a dose of 0.5 mg/kg/day once daily up to a maximum of 25 mg/day on Days 2, 3, 5, and 7 as rescue medication for asthma exacerbation at the discretion of the investigator.

SCH 697243

Grass Sublingual Tablet (Phleum pratense extract)

Group Type: EXPERIMENTAL

SCH 697243

Intervention Type: BIOLOGICAL

Grass sublingual tablet, once daily

Loratadine Syrup 1 mg/mL Rescue Treatment

Intervention Type: DRUG

Loratadine Syrup 1 mg/mL was dosed orally once daily at a dose of 5 mg for children aged 5 to \<6 years of age and at a dose of 10 mg for children aged 6 to \<18 years of age as rescue medication for symptoms of rhinoconjunctivitis among participants with a total symptom score ≥4.

Loratadine 10 mg Rescue Treatment

Intervention Type: DRUG

Loratadine 10 mg RediTabs tablets were dosed orally once daily at a dose of 10 mg for children aged 6 to \<18 years of age as rescue medication for symptoms of rhinoconjunctivitis among participants with a total symptom score ≥4.

Olopatadine 0.1% Rescue Treatment

Intervention Type: DRUG

Olopatadine hydrochloride 0.1% ophthalmic solution was dosed intraocularly at a dose of 1 drop in each affected eye twice daily, in addition to loratadine, as rescue medication for participants with persistent eye symptoms due to rhinoconjunctivitis.

Mometasone furoate 50 mcg Rescue Treatment

Intervention Type: DRUG

Mometasone furoate monohydrate nasal spray 50 mcg was dosed intranasally at a dose of one spray in each nostril once daily for participants aged 5 to \<12 years and a dose of 2 sprays in each nostril once daily for participants aged 12 to \<18 years as rescue medication for nasal symptoms of rhinoconjunctivitis among participants with a total symptom score of ≥4 despite loratadine and mometasone furoate nasal spray.

Albuterol 108 mcg Rescue Treatment

Intervention Type: DRUG

Albuterol sulfate inhalation aerosol 108 mcg/inhalation was administered via inhalation at a dose of 2 inhalations every 4 to 6 hours as rescue medication among participants aged 5 to \<18 years with asthma symptoms .

Fluticasone 44 mcg Rescue Treatment

Intervention Type: DRUG

Fluticasone propionate inhalation aerosol 44 mcg/inhalation was administered via inhalation at a dose of 2 inhalations twice daily among participants aged 12 to \<18 years up to a maximum dose of 10 inhalations twice daily, in combination with albuterol, among participants with ≥4 albuterol sulfate inhalations/day for 2 days as rescue medication for nocturnal asthma or shortness of breath.

Prednisone 5 mg Rescue Treatment

Intervention Type: DRUG

Prednisone tablet 5 mg was administered orally at a dose of 1 mg/kg/day once daily up to a maximum of 50 mg/day on Day 1, and at a dose of 0.5 mg/kg/day once daily up to a maximum of 25 mg/day on Days 2, 3, 5, and 7 as rescue medication for asthma exacerbation at the discretion of the investigator.

Interventions

Placebo

Placebo sublingual tablet, once daily

Intervention Type: DRUG

SCH 697243

Grass sublingual tablet, once daily

Intervention Type: BIOLOGICAL

Loratadine Syrup 1 mg/mL Rescue Treatment

Loratadine Syrup 1 mg/mL was dosed orally once daily at a dose of 5 mg for children aged 5 to \<6 years of age and at a dose of 10 mg for children aged 6 to \<18 years of age as rescue medication for symptoms of rhinoconjunctivitis among participants with a total symptom score ≥4.

Intervention Type: DRUG

Loratadine 10 mg Rescue Treatment

Loratadine 10 mg RediTabs tablets were dosed orally once daily at a dose of 10 mg for children aged 6 to \<18 years of age as rescue medication for symptoms of rhinoconjunctivitis among participants with a total symptom score ≥4.

Intervention Type: DRUG

Olopatadine 0.1% Rescue Treatment

Olopatadine hydrochloride 0.1% ophthalmic solution was dosed intraocularly at a dose of 1 drop in each affected eye twice daily, in addition to loratadine, as rescue medication for participants with persistent eye symptoms due to rhinoconjunctivitis.

Intervention Type: DRUG

Mometasone furoate 50 mcg Rescue Treatment

Mometasone furoate monohydrate nasal spray 50 mcg was dosed intranasally at a dose of one spray in each nostril once daily for participants aged 5 to \<12 years and a dose of 2 sprays in each nostril once daily for participants aged 12 to \<18 years as rescue medication for nasal symptoms of rhinoconjunctivitis among participants with a total symptom score of ≥4 despite loratadine and mometasone furoate nasal spray.

Intervention Type: DRUG

Albuterol 108 mcg Rescue Treatment

Albuterol sulfate inhalation aerosol 108 mcg/inhalation was administered via inhalation at a dose of 2 inhalations every 4 to 6 hours as rescue medication among participants aged 5 to \<18 years with asthma symptoms .

Intervention Type: DRUG

Fluticasone 44 mcg Rescue Treatment

Fluticasone propionate inhalation aerosol 44 mcg/inhalation was administered via inhalation at a dose of 2 inhalations twice daily among participants aged 12 to \<18 years up to a maximum dose of 10 inhalations twice daily, in combination with albuterol, among participants with ≥4 albuterol sulfate inhalations/day for 2 days as rescue medication for nocturnal asthma or shortness of breath.

Intervention Type: DRUG

Prednisone 5 mg Rescue Treatment

Prednisone tablet 5 mg was administered orally at a dose of 1 mg/kg/day once daily up to a maximum of 50 mg/day on Day 1, and at a dose of 0.5 mg/kg/day once daily up to a maximum of 25 mg/day on Days 2, 3, 5, and 7 as rescue medication for asthma exacerbation at the discretion of the investigator.

Intervention Type: DRUG

Other Intervention Names

Phleum pratense extract; Claritin; Claritin; Pantanol; Nasonex; Proventil; Ventolin; Volmax; Vospire; Flonase; Deltasone; Meticorten; Orasone; Prednicen-M; Prednicot; Sterapred; Sterapred DS

Eligibility Criteria

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ALK-Abelló A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Blaiss M, Maloney J, Nolte H, Gawchik S, Yao R, Skoner DP. Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents. J Allergy Clin Immunol. 2011 Jan;127(1):64-71, 71.e1-4. doi: 10.1016/j.jaci.2010.11.034.

Reference Type: RESULT

PMID: 21211642 (View on PubMed)

Hebert J, Blaiss M, Waserman S, Kim H, Creticos P, Maloney J, Kaur A, Li Z, Nelson H, Nolte H. The efficacy and safety of the Timothy grass allergy sublingual immunotherapy tablet in Canadian adults and children. Allergy Asthma Clin Immunol. 2014 Oct 30;10(1):53. doi: 10.1186/1710-1492-10-53. eCollection 2014.

Reference Type: DERIVED

PMID: 25685162 (View on PubMed)

Other Identifiers

3733251

Identifier Type: -

Identifier Source: secondary_id

P05239

Identifier Type: -

Identifier Source: org_study_id