Allergic RhinitisNCT04078009
Standardising Nasal Allergen Challenge in Adult With Hay Fever
A study testing Aquagen and Grazax in people with Allergic Rhinitis, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Hay fever affects 1 in 4 of the UK population and has significant effects on the quality of life of sufferers. Allergy to grass pollen is the most common cause. A detailed understanding of the mechanisms involved during allergic reactions to pollens in hay fever sufferers may provide improvements in diagnosis, drug… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Allergic Rhinitis
- What is being tested?
- Aquagen and Grazax
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 26 Sep 2019to 28 Aug 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults age 18 to 65 years.
- A clinical history of moderate-severe grass pollen-induced allergic rhino conjunctivitis for at least 2 years with peak symptoms from mid-May to mid-July.
- Positive skin prick test response, defined as wheal diameter ≥ 5 mm, to timothy grass pollen.
- For women of childbearing age, a negative urine pregnancy test at the time of screening and willingness to use an effective form of contraception for the duration of involvement in the study.
- The ability to give informed consent and comply with study procedures.
Who cannot join
- History of previous grass pollen allergen immunotherapy at any time in the past.
- Pre-bronchodilator FEV1 < 70% of predicted value at screening.
- A clinical history of symptomatic allergic rhinitis and/or asthma caused by an allergen other than grass pollen to which the participant is regularly exposed either seasonally (eg. tree pollen, weed pollen and moulds) or perennially (house dust mite, cat, dog dander).
- Perennial asthma requiring regular inhaled corticosteroids.
- History of emergency visit or hospital admission for asthma in the previous 12 months.
- History of chronic obstructive pulmonary disease
Show all 14Show fewer
- History of significant recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment.
- History of chronic sinusitis, defined as sinus symptoms lasting greater than 12 weeks that includes 2 or more major factors or 1 major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, ear pain, pressure, or fullness.
- At screening visit, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve.
- History of life-threatening anaphylaxis or angioedema.
- Ongoing systemic immunosuppressive treatment.
- The use of any investigational drug within 30 days of the screening visit.
- The presence of any medical condition that the investigator deems incompatible with participation in the study.
- History of fish allergy with positive skin test and/or positive specific IgE test to vertebrate/finned fish (due to potential fish allergen exposure from fish-gelatin in Grazax).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Nasal Allergen Challenge: Standardisation as a Surrogate for Hay Fever
Hay fever affects 1 in 4 of the UK population and has significant effects on the quality of life of sufferers. Allergy to grass pollen is the most common cause. A detailed understanding of the mechanisms involved during allergic reactions to pollens in hay fever sufferers may provide improvements in diagnosis, drug treatment and assessment of their response to treatment.
Controlled exposures to allergens such as grass pollen can provide important information on the mechanisms of allergic inflammation and may be used to assess the success of anti-allergy treatments.
Read more
Nasal allergen challenge (NAC) is a useful tool in the investigation of allergic rhinitis, including grass pollen-induced seasonal allergic rhinitis (hay fever). NAC is performed by installation of a very small amount of grass pollen extract into the nose in order to reproduce mild and short-lived symptoms such as nasal itch, sneezing, runny nose and nasal congestion that you experience in a more severe form during natural exposure to grass pollen during the summer. Nasal allergen challenge has allowed us to explore the mechanism of hay fever and to provide a rapid and reliable method for investigating new potential treatments for hay fever.
Nasal allergen Challenge is a very well-standardised and safe procedure that has been performed within the department of Allergy and Clinical Immunology at Imperial College and Royal Brompton Hospital for many years.
Unfortunately the grass pollen extract ('Aquagen') that we have routinely used for nasal challenge has been discontinued and is therefore no longer available. The present study involves testing an alternative source of the grass pollen extract in the form of 'Grazax' which is a freeze-dried tablet that is highly standardised and should enable us to give an identical amount of grass pollen extract for the purpose of nasal challenge. We plan a 'head-to-head' comparison of the two extracts in nasal challenge in order to confirm that the two sources of allergen are equivalent thereby enabling us to use Grazax as the source of grass pollen extract for our nasal challenge studies in the future.
Read the detailed description
Nasal allergen challenge (NAC) is a useful tool in the investigation of allergic rhinitis, including grass pollen-induced seasonal allergic rhinitis (hay fever). We have experience in using NAC to investigate the clinical and immunological effects of allergen exposure and in using NAC as a surrogate outcome to assess the efficacy of treatments for allergic rhinitis. The procedure is safe and well tolerated. In order for NAC to be a valid tool, it is essential that the allergen extracts used are standardised in terms of concentration and stability in solution. We have previously used an extract of Timothy Grass (Phleum pratense) pollen, Aquagen (ALK-Abello, Denmark). Aquagen is supplied as a dry powder, to be reconstituted prior to use by dissolving in an albumin-based diluent. Unfortunately, Aquagen production has been discontinued, but the identical allergen is now available as Timothy Grass lyophilisate tablet, Grazax (ALK-Abello), an approved and licensed product for treatment of severe seasonal allergic rhinitis. Grazax consists of purified, freeze-dried Timothy Grass pollen extract, plus only three excipients, gelatin (from fish), mannitol and sodium hydroxide. Preliminary investigations have shown that Grazax tablets can be dissolved in saline to produce identical concentrations of allergen to Aquagen, with the same stability profile in vitro. We anticipate therefore, that the clinical effect when used for nasal allergen challenges would be equivalent to the use of Aquagen for a given allergen concentration. In this study we intend to confirm that nasal symptoms produced during the NAC with either Aquagen or Grazax will be equivalent. We will recruit volunteers with grass pollen-induced hay fever to undergo NAC with each allergen source, sequentially. In an open, randomised-order, cross-over study. The primary outcome will be patient-reported nasal symptoms (according to a standardised scoring system) in the 60 minutes after each nasal challenge.
- Conditions
- Allergic Rhinitis
- Being tested
- Aquagen, Grazax
- Keywords
- Grass pollen allergy, Hayfever, Atopy, Allergic rhinitis, Nasal allergen challenge
- Medical subject headings
- Rhinitis, Allergic, Rhinitis, Allergic, Seasonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AquagenDiagnostic test
Also called Grazax Timothy Grass lyophilisate tablet
To compare the clinical allergic response after direct installation of an aqueous solution of Aquagen Timothy Grass pollen extract via nasal allergen challenge with the clinical allergic response after direct installation of an aqueous solution of Grazax Timothy Grass lyophilisate tablets via nasal allergen challenge in grass pollen allergic individuals.
GrazaxDiagnostic test
To compare the clinical allergic response after direct installation of an aqueous solution of Aquagen Timothy Grass pollen extract via nasal allergen challenge with the clinical allergic response after direct installation of an aqueous solution of Grazax Timothy Grass lyophilisate tablets via nasal allergen challenge in grass pollen allergic individuals.
| Study group | Role | What they receive |
|---|---|---|
| Aquagen (Starts with Aquagen and finish with Grazax) | Experimental | In order to explore a possible order effect with the challenges, in this single group cross-over trial, participants will be randomised (by computer-generated randomisation) to receive either Aquagen or Grazax as the first challenge, followed by the other allergen extract at the second challenge a minimum of 4 weeks later. Receives: Diagnostic Test: Aquagen |
| Grazax (Starts with Grazax and finish with Aquagen) | Experimental | In order to explore a possible order effect with the challenges, in this single group cross-over trial, participants will be randomised (by computer-generated randomisation) to receive either Aquagen or Grazax as the first challenge, followed by the other allergen extract at the second challenge a minimum of 4 weeks later. Receives: Diagnostic Test: Grazax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total nasal symptoms scores after nasal allergen challenge
To compare the total nasal symptom score at one hour after grass pollen nasal allergen challenge in Aquagen group versus Grazax group. Score ranges from 0-12 points. Higher score is more severe symptoms.
Measured: 60 minutes
Secondary outcomes (2)
Peak nasal inspiratory flow
Area under the curve for peak nasal inspiratory flow (PNIF) (delta PNIF change from baseline) 0-60 minutes post NAC. Bland Altman plots will also be utilized for the analysis of the secondary endpoint of delta PNIF AUC.
Measured: Baseline, 60 minutes
Incidence of Adverse Events
To evaluate the safety and tolerability of the nasal allergen challenge administered with each allergen source (Aquagen or Grazax). Participant and investigator reported adverse events potentially related to study procedures, including nasal allergen challenge, will be recorded (typical symptoms of hay fever following nasal allergen challenge lasting less than 24 hours will not be considered adverse events). Frequency of adverse events will be tabulated by event, system organ class, severity, and procedure relatedness as per CTCAE v4.0.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2019
- Study start26 Sep 2019
- Primary completion29 May 2020
- Study completion28 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Allergic RhinitisStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is a single group study assessing symptoms scores 4 weeks between the two assessments (Grazax NAC and Aquagen NAC) performed to avoid any carry-over effects of this cross-over design.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Prof Stephen Durham, MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04078009
- Sponsor's protocol ID
- 19IC5338
- Status last verified
- Aug 2021
- First submitted
- 28 Aug 2019
- Last updated
- 31 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nasal Allergen Challenge: Standardisation as a Surrogate for Hay Fever
- ClinicalTrials.gov ID
- NCT04078009
- Acronym / sponsor ID
- 19IC5338
- Conditions
- Allergic Rhinitis
- Keywords
- Grass pollen allergy, Hayfever, Atopy, Allergic rhinitis, Nasal allergen challenge
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- 29 May 2020 (actual)
- Study completion
- 28 Aug 2020 (actual)
- First posted
- 4 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hay fever affects 1 in 4 of the UK population and has significant effects on the quality of life of sufferers. Allergy to grass pollen is the most common cause. A detailed understanding of the mechanisms involved during allergic reactions to pollens in hay fever sufferers may provide improvements in diagnosis, drug treatment and assessment of their response to treatment.
Controlled exposures to allergens such as grass pollen can provide important information on the mechanisms of allergic inflammation and may be used to assess the success of anti-allergy treatments.
Nasal allergen challenge (NAC) is a useful tool in the investigation of allergic rhinitis, including grass pollen-induced seasonal allergic rhinitis (hay fever). NAC is performed by installation of a very small amount of grass pollen extract into the nose in order to reproduce mild and short-lived symptoms such as nasal itch, sneezing, runny nose and nasal congestion that you experience in a more severe form during natural exposure to grass pollen during the summer. Nasal allergen challenge has allowed us to explore the mechanism of hay fever and to provide a rapid and reliable method for investigating new potential treatments for hay fever.
Nasal allergen Challenge is a very well-standardised and safe procedure that has been performed within the department of Allergy and Clinical Immunology at Imperial College and Royal Brompton Hospital for many years.
Unfortunately the grass pollen extract ('Aquagen') that we have routinely used for nasal challenge has been discontinued and is therefore no longer available. The present study involves testing an alternative source of the grass pollen extract in the form of 'Grazax' which is a freeze-dried tablet that is highly standardised and should enable us to give an identical amount of grass pollen extract for the purpose of nasal challenge. We plan a 'head-to-head' comparison of the two extracts in nasal challenge in order to confirm that the two sources of allergen are equivalent thereby enabling us to use Grazax as the source of grass pollen extract for our nasal challenge studies in the future.
Detailed description
Nasal allergen challenge (NAC) is a useful tool in the investigation of allergic rhinitis, including grass pollen-induced seasonal allergic rhinitis (hay fever). We have experience in using NAC to investigate the clinical and immunological effects of allergen exposure and in using NAC as a surrogate outcome to assess the efficacy of treatments for allergic rhinitis. The procedure is safe and well tolerated. In order for NAC to be a valid tool, it is essential that the allergen extracts used are standardised in terms of concentration and stability in solution. We have previously used an extract of Timothy Grass (Phleum pratense) pollen, Aquagen (ALK-Abello, Denmark). Aquagen is supplied as a dry powder, to be reconstituted prior to use by dissolving in an albumin-based diluent. Unfortunately, Aquagen production has been discontinued, but the identical allergen is now available as Timothy Grass lyophilisate tablet, Grazax (ALK-Abello), an approved and licensed product for treatment of severe seasonal allergic rhinitis. Grazax consists of purified, freeze-dried Timothy Grass pollen extract, plus only three excipients, gelatin (from fish), mannitol and sodium hydroxide. Preliminary investigations have shown that Grazax tablets can be dissolved in saline to produce identical concentrations of allergen to Aquagen, with the same stability profile in vitro. We anticipate therefore, that the clinical effect when used for nasal allergen challenges would be equivalent to the use of Aquagen for a given allergen concentration. In this study we intend to confirm that nasal symptoms produced during the NAC with either Aquagen or Grazax will be equivalent. We will recruit volunteers with grass pollen-induced hay fever to undergo NAC with each allergen source, sequentially. In an open, randomised-order, cross-over study. The primary outcome will be patient-reported nasal symptoms (according to a standardised scoring system) in the 60 minutes after each nasal challenge.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a single group study assessing symptoms scores 4 weeks between the two assessments (Grazax NAC and Aquagen NAC) performed to avoid any carry-over effects of this cross-over design.
| Arm | Type | Receives |
|---|---|---|
| Aquagen (Starts with Aquagen and finish with Grazax) | Experimental | Diagnostic Test: AquagenIn order to explore a possible order effect with the challenges, in this single group cross-over trial, participants will be randomised (by computer-generated randomisation) to receive either Aquagen or Grazax as the first challenge, followed by the other allergen extract at the second challenge a minimum of 4 weeks later. |
| Grazax (Starts with Grazax and finish with Aquagen) | Experimental | Diagnostic Test: GrazaxIn order to explore a possible order effect with the challenges, in this single group cross-over trial, participants will be randomised (by computer-generated randomisation) to receive either Aquagen or Grazax as the first challenge, followed by the other allergen extract at the second challenge a minimum of 4 weeks later. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults age 18 to 65 years.
- A clinical history of moderate-severe grass pollen-induced allergic rhino conjunctivitis for at least 2 years with peak symptoms from mid-May to mid-July.
- Positive skin prick test response, defined as wheal diameter ≥ 5 mm, to timothy grass pollen.
- For women of childbearing age, a negative urine pregnancy test at the time of screening and willingness to use an effective form of contraception for the duration of involvement in the study.
- The ability to give informed consent and comply with study procedures.
Key exclusion criteria (14 listed)
- History of previous grass pollen allergen immunotherapy at any time in the past.
- Pre-bronchodilator FEV1 < 70% of predicted value at screening.
- A clinical history of symptomatic allergic rhinitis and/or asthma caused by an allergen other than grass pollen to which the participant is regularly exposed either seasonally (eg. tree pollen, weed pollen and moulds) or perennially (house dust mite, cat, dog dander).
- Perennial asthma requiring regular inhaled corticosteroids.
- History of emergency visit or hospital admission for asthma in the previous 12 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AquagenAlso: Grazax Timothy Grass lyophilisate tabletTo compare the clinical allergic response after direct installation of an aqueous solution of Aquagen Timothy Grass pollen extract via nasal allergen challenge with the clinical allergic response after direct installation of an aqueous solution of Grazax Timothy Grass lyophilisate tablets via nasal allergen challenge in grass pollen allergic individuals. | Diagnostic test | Aquagen (Starts with Aquagen and finish with Grazax) |
| GrazaxTo compare the clinical allergic response after direct installation of an aqueous solution of Aquagen Timothy Grass pollen extract via nasal allergen challenge with the clinical allergic response after direct installation of an aqueous solution of Grazax Timothy Grass lyophilisate tablets via nasal allergen challenge in grass pollen allergic individuals. | Diagnostic test | Grazax (Starts with Grazax and finish with Aquagen) |
Primary outcome
Total nasal symptoms scores after nasal allergen challenge
Time frame: 60 minutes
To compare the total nasal symptom score at one hour after grass pollen nasal allergen challenge in Aquagen group versus Grazax group. Score ranges from 0-12 points. Higher score is more severe symptoms.
2 secondary outcomes
Peak nasal inspiratory flow
Time frame: Baseline, 60 minutes
Incidence of Adverse Events
Time frame: 48 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof Stephen Durham, MD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aquagen and Grazax in people with Allergic Rhinitis, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total nasal symptoms scores after nasal allergen challenge (time frame: 60 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2021.