Ignite Creation Date:
2024-05-06 @ 2:16 AM
Last Modification Date:
2024-10-26 @ 11:16 AM
Study NCT ID:
NCT02005627
Status:
COMPLETED
Last Update Posted:
2019-12-04
First Post:
2013-12-04
Brief Title:
Grass Pollen Allergen Immunotherapy Tablet AIT Time Course Study
Sponsor:
Imperial College London
Organization:
Imperial College London
Study Overview
Official Title:
Randomised Placebo-controlled Study of Grass Pollen Allergen Immunotherapy Tablet AIT for Seasonal Rhinitis Time Course of Nasal Cutaneous and Immunological Outcomes
Status:
COMPLETED
Status Verified Date:
2019-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Pollen
Brief Summary:
About 45 million people in Europe have allergic rhinitis hay fever - inflammation of the nasal passages causing sneezing runny nose nasal congestion itching and tearing of the eyes In the United Kingdom UK seasonal hay fever due to grass pollen allergy accounts for approximately 7 times more doctors appointments than asthma The standard treatment for hay fever consists of treating the symptoms with a nasal spray and an antihistamine However in a survey taken in a UK general practice less than 40 of patients with hay fever reported good symptom control with this standard treatment For those patients with hay fever whose symptoms are not well controlled by treatment with antihistamines and nasal sprays subcutaneous immunotherapy SCIT - monthly injections of a grass allergen extract for a period of 3-5 years is an effective alternative and is approved in the UK on a named patient basis More recently allergen immunotherapy tablets AITs have been developed including grass pollen allergen tablets These have been shown to be highly effective in the treatment of hay fever with the additional benefit of being convenient for patients given that they may be taken at home Grazax manufactured by Allergologisk Laboratorium København ALK-Abello Denmark has UK and European Union EU license for use in the treatment of troublesome grass pollen induced hay fever The aim of this research is to investigate the effects of the AIT treatment on the immune system over time - which changes are taking place and when in the course of treatment This will provide insight into the complexities of the development of allergen-specific immune tolerance - how harmful allergic responses against innocuous substances such as grass pollen can be overridden
Detailed Description:
The study will be conducted over 44 months We expect to screen 70 atopic patients in order to enroll up to 50 suitable atopic participants to ensure randomisation of at least 40 atopic participants following their baseline visit Additionally we shall recruit 20 healthy non-atopic volunteers Individuals with moderate to severe grass pollen hay fever with or without associated seasonal asthma will be recruited and screened after the pollen season from September through March 2014 Atopic Participants will undergo baseline assessments in December 2013 to March 2014 All screening assessments will be completed before eligible participants are randomized to active or placebo treatment Atopic participants will then begin AIT treatment in February-March 2014 and continue treatment for 12 months All atopic participants will be provided with anti-allergic rescue medications antihistamine tablets topical intranasal corticosteroids and eye-drops throughout the pollen season Clinical surrogate endpoint assessments and on specific time Points blood nasal fluid and nasal brushing sampling will be performed at baseline January-March 2014 at 4 8 12 and 16 weeks after starting the AIT and at 6 and at 12 months January-March 2015 of treatment Nasal mucosal biopsies will be taken at baseline during the Peak pollen season and 12 months of treatment After 12 months of treatment unblinding will take place Those atopic participants receiving active AIT treatment will continue therapy for another 12 months followed by a withdrawal phase of 12 months Blood samples and nasal biopsies will be taken from these participants again at 24 and at 36 months from the initial start of treatment Those atopic participants on placebo will be offered 24 months of active treatment after unblinding
20 healthy non-atopic participants will also be recruited and studied on a single day before and after nasal challenge at one timepoint at 12 months They will undergo the same clinical and immunological measurements as for the 46 randomised subjects participating in the clinical trial The healthy subjects will undergo no therapeutic intervention and serve as controls for the immunological measurements
The study will receive monitoring by
the sponsor Imperial College London
and audits by
Medicines for human use clinical trials regulations authority MHRA
We will assess the clinical data on paper case report forms and will use Inform as a database in order to verify completeness of data entry
The Inform database also includes normal ranges of parameters if relevant
Standard Operating Procedures are in place regarding clinical measures eg nasal allergen challenges nasal biopsies etc as well as data management eg the Trial Master File reporting of adverse events and data collection All involved investigators are informed about these procedures and have current Good Clinical Practice GMC instructions
Statistical analysis will be with non-parametric statistics taking into account treatment effect baseline values and visit number Inclusion of 20 participants per group will give greater than 90 power p005 to detect a 40 reduction in the early phase response EPR after nasal challenge AUC of the TNSS in the first 60 minutes after challenge a 40 reduction in the skin late phase response LPR and a 50 increase in grass pollen allergen specific immunoglobulin G4 IgG4 for AIT vs placebo
Based on more recent nasal allergen challenge studies Scadding et al unpublished data mean 463 standard deviation 165 for AUC 0-60 minutes post grass pollen nasal challenge in 14 allergic volunteers inclusion of 13 patients per group will provide 80 power to detect a 40 reduction in AUC after challenge whereas inclusion of 22 patients per group will provide 80 power to detect a 30 reduction
Further based on a recent study Scadding et al unpublished data mean 7014 standard deviation 1417 for cross-sectional area in cm2 at 8 hours for skin late phase response to intradermal grass pollen injection inclusion of 7 participants per group will provide 80 power to detect a 30 reduction whereas inclusion of 10 participants per group will provide 90 power to detect a 30 reduction
Intent-to-treat ITT sample will be defined as all randomized participants ITT participants will be analysed with the group to which they were randomized regardless of the medication actually received If participants drop out post randomisation they will be invited to complete study assessments throughout the duration of the trial
Per-protocol PP sample will be defined as ITT sample participants who remain in the study for 12 months and in whom the primary endpoints were assessed Participants in the PP sample must be compliant with study medication defined as taking 75 or more of their study medication for the duration of the study Compliance with study medication will be as assessed by pill count for returned AITplacebo Participants in the PP sample will be analysed with the group to which they were randomized The non-atopics will also be included in the PP sample
Safety sample SS will be defined as all enrolled participants
Analysis of study data will be conducted to address all objectives of the trial and other interrelationships among all data elements of interest to the investigators and of relevance to the objectives of the study Primary analysis of treatment effect will be conducted under the intention-to-treat ITT principle of eligible patients whereby outcome data from all eligible patients will be included regardless of treatment compliance In addition to the analyses described in sections below summary descriptive statistics will be provided in the following manner continuous data will be summarized descriptively by mean standard deviation median and range categorical data will be presented as enumerations and percentages
Analysis of primary endpoint
The primary endpoint will be analysed using the ITT and the PP sample The analysis of the primary endpoint will compare the mean EPR to nasal challenge recorded by the TNSS during the first 60 minutes after the nasal challenge at 12 months of therapy Comparison between active and placebo groups will be assessed using ANOVA at the 005 level of significance
Analysis of secondary endpoint
All secondary analyses will be treated as supportive P-values will be presented for the secondary endpoints but will not be adjusted for multiplicity and should be interpreted with caution Findings will be evaluated in the context of the available body of knowledge and with respect to other findings
20 healthy non-atopic participants will also be recruited and studied on a single day before and after nasal challenge at one timepoint at 12 months They will undergo the same clinical and immunological measurements as for the 46 randomised subjects participating in the clinical trial The healthy subjects will undergo no therapeutic intervention and serve as controls for the immunological measurements
The study will receive monitoring by
the sponsor Imperial College London
and audits by
Medicines for human use clinical trials regulations authority MHRA
We will assess the clinical data on paper case report forms and will use Inform as a database in order to verify completeness of data entry
The Inform database also includes normal ranges of parameters if relevant
Standard Operating Procedures are in place regarding clinical measures eg nasal allergen challenges nasal biopsies etc as well as data management eg the Trial Master File reporting of adverse events and data collection All involved investigators are informed about these procedures and have current Good Clinical Practice GMC instructions
Statistical analysis will be with non-parametric statistics taking into account treatment effect baseline values and visit number Inclusion of 20 participants per group will give greater than 90 power p005 to detect a 40 reduction in the early phase response EPR after nasal challenge AUC of the TNSS in the first 60 minutes after challenge a 40 reduction in the skin late phase response LPR and a 50 increase in grass pollen allergen specific immunoglobulin G4 IgG4 for AIT vs placebo
Based on more recent nasal allergen challenge studies Scadding et al unpublished data mean 463 standard deviation 165 for AUC 0-60 minutes post grass pollen nasal challenge in 14 allergic volunteers inclusion of 13 patients per group will provide 80 power to detect a 40 reduction in AUC after challenge whereas inclusion of 22 patients per group will provide 80 power to detect a 30 reduction
Further based on a recent study Scadding et al unpublished data mean 7014 standard deviation 1417 for cross-sectional area in cm2 at 8 hours for skin late phase response to intradermal grass pollen injection inclusion of 7 participants per group will provide 80 power to detect a 30 reduction whereas inclusion of 10 participants per group will provide 90 power to detect a 30 reduction
Intent-to-treat ITT sample will be defined as all randomized participants ITT participants will be analysed with the group to which they were randomized regardless of the medication actually received If participants drop out post randomisation they will be invited to complete study assessments throughout the duration of the trial
Per-protocol PP sample will be defined as ITT sample participants who remain in the study for 12 months and in whom the primary endpoints were assessed Participants in the PP sample must be compliant with study medication defined as taking 75 or more of their study medication for the duration of the study Compliance with study medication will be as assessed by pill count for returned AITplacebo Participants in the PP sample will be analysed with the group to which they were randomized The non-atopics will also be included in the PP sample
Safety sample SS will be defined as all enrolled participants
Analysis of study data will be conducted to address all objectives of the trial and other interrelationships among all data elements of interest to the investigators and of relevance to the objectives of the study Primary analysis of treatment effect will be conducted under the intention-to-treat ITT principle of eligible patients whereby outcome data from all eligible patients will be included regardless of treatment compliance In addition to the analyses described in sections below summary descriptive statistics will be provided in the following manner continuous data will be summarized descriptively by mean standard deviation median and range categorical data will be presented as enumerations and percentages
Analysis of primary endpoint
The primary endpoint will be analysed using the ITT and the PP sample The analysis of the primary endpoint will compare the mean EPR to nasal challenge recorded by the TNSS during the first 60 minutes after the nasal challenge at 12 months of therapy Comparison between active and placebo groups will be assessed using ANOVA at the 005 level of significance
Analysis of secondary endpoint
All secondary analyses will be treated as supportive P-values will be presented for the secondary endpoints but will not be adjusted for multiplicity and should be interpreted with caution Findings will be evaluated in the context of the available body of knowledge and with respect to other findings
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 13EM0351 | OTHER | United Kingdom UK Research Ethics Committee | None |
| 2013-003732-72 | EUDRACT_NUMBER | None | None |