Chronic Idiopathic UrticariaPhase 2NCT02031679
Efficacy and Safety of Chemoattractant Receptor-homologous Molecule Expressed on T Helper Type 2 (CRTh2) Antagonist AZD1981 in Chronic Idiopathic Urticaria (CIU) Antihistamines
A Phase 2 study testing AZD1981 in people with Chronic Idiopathic Urticaria, run by Johns Hopkins University at 1 site in United States.
Trial summary
The investigators are recruiting for a chronic hives study. This research is being done to test whether an investigational drug called AstraZeneca drug (AZD)1981 may be helpful for treating people with Chronic Idiopathic Urticaria who continue to have symptoms despite taking antihistamines. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Idiopathic Urticaria
- What is being tested?
- AZD1981
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Jan 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Females must be surgically sterile or postmenopausal or using a highly effective form of birth control throughout the duration of the study
- Females must have a negative urine pregnancy test at screening
- Must meet the criteria for Chronic Idiopathic Urticaria (CIU) as defined by itching and hives for >3 days per week for over 6 weeks with no clear cause
- CIU symptoms must have started at least 6 months prior to starting the study
- Must have moderate to severe CIU, using a standardized survey, despite taking antihistamines
Who cannot join
- Pregnant females or females who plan to become pregnant during the study
- Drug or alcohol abuse within the past 3 years
- Use of any investigational drug with 30 days of the start of the study
- Eczema or other skin conditions associated with itching (besides hives)
- Inability to comply with follow-up procedures
- Use of the following therapies in the past 30 days: hydroxychloroquine, sulfasalazine, dapsone, methotrexate, cyclophosphamide, Intravenous Immunoglobulin (IVIG), plasmapheresis, cyclosporine, oral or systemic steroids, or other monoclonal antibody therapies
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- Use of doxepin within the past 2 weeks
- Use of either H2 antihistamines and leukotriene receptor antagonists within 7 days before starting the study (unless already on these medications for Gastroesophageal Reflux Disease (GERD), asthma or allergic rhinitis)
- Inability to take diphenhydramine (Benadryl)
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks or interfere with ability to comply with study procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Asthma and Allergy Center
Baltimore, Maryland, 21224-6821
About this study
Official title: A Phase IIa, Randomized, Placebo-controlled, Double-blind Study to Assess the Efficacy and Safety of the CRTh2 Antagonist AZD1981 in Patients With Chronic Idiopathic Urticaria (CIU) Who Are Refractory to H1 Antihistamines
The investigators are recruiting for a chronic hives study. This research is being done to test whether an investigational drug called AstraZeneca drug (AZD)1981 may be helpful for treating people with Chronic Idiopathic Urticaria who continue to have symptoms despite taking antihistamines. The word "investigational" means that AZD1981 is not approved for marketing by the Food and Drug Administration (FDA). The FDA is allowing the use of AZD1981 in this study.
People with chronic hives lasting for at least 6 months and without a known cause may join. The study involves 6 visits over 8 weeks. Approximately 48 participants expected to take part in this study at the Johns Hopkins Asthma and Allergy Clinic. All participants will be treated with the study medication and/or placebo for 8 weeks.
The results of this trial may have a benefit others with Chronic Idiopathic Urticaria who don't respond well to antihistamines by generating experience and data to support the design of a larger, multicenter trial investigating the efficacy of AZD1981 in treating antihistamine refractory CIU.
Read the detailed description
The investigators propose to use AZD1981 in subjects with chronic idiopathic urticaria (CIU) who are otherwise uncontrolled on first-line, oral antihistamine therapy. The skin lesion pathology in CIU shows a perivascular infiltrate of lymphocytes (both Th2 and Th1), eosinophils, and basophils, and closely resembles an allergen-induced late-phase reaction. Further, murine studies show that the chemoattractant receptor-homologous molecule expressed on Th2 (CRTh2) pathway is important in leukocyte recruitment following allergen challenge of the skin. Our proposed hypothesis is that AZD1981 in CIU will reduce CRTh2-expressing, leukocyte recruitment to the skin and reduce leukocyte activation through CRTh2, thus reducing the signs and symptoms in CIU refractory to control with antihistamines.
- Conditions
- Chronic Idiopathic Urticaria
- Being tested
- AZD1981, Placebo
- Keywords
- Chronic Idiopathic Urticaria
- Medical subject headings
- Chronic Urticaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD1981Drug
Also called Oral CRTh2 antagonist
AZD1981 is an oral, potent, selective, reversible antagonist of CRTh2 (Chemoattractant Receptor Homologous Molecule expressed on Th2 cells).
PlaceboDrug
Sugar pill manufactured to mimic AZD1981 10 mg tablet
| Study group | Role | What they receive |
|---|---|---|
| AZD1981 | Experimental | AZD1981 for oral administration will be available in tablet form. AZD1981 tablets will be provided in 10 mg strengths.
The drug will be self-administered by the subject. Subjects will take 4 tablets in the morning, 4 tablets in the afternoon, and 4 tablets in the evening.
The tablets should be swallowed whole with a glass of water. Receives: Drug: AZD1981 |
| Placebo | Placebo comparator | The placebo will be available in tablet form. The placebo contains the same ingredients as the AZD1981 with the exception of the active compound.
The placebo will be self-administered by the subject. Subjects will take 4 tablets in the morning, 4 tablets in the afternoon, and 4 tablets in the evening.
The tablets should be swallowed whole with a glass of water. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7)
The UAS score, which is the sum of pruritus and hives, will be used to calculate the UAS7. UAS is a validated measure of Chronic Spontaneous Urticaria (CSU) disease activity which scores the intensity of pruritus (0-3, with 0 = no itch and 3 is severe itch) and number of hives (0-3 0 means no hives and 3 means greater than 50 hives) with a maximum value of 6 for a given day. The UAS7 is the sum of the daily average UAS scores (average of a.m. and p.m.) for 7 days with a minimum score of 0 and a maximum value of 42. The UAS7 is a sum of the daily average (average of a.m. and p.m.) for 7 days. The baseline score was established during the second placebo therapy week and compared to the final week of the 4 week active treatment period.
Measured: 7 Days
Secondary outcomes (2)
The Number of Participants With Adverse Events
The safety of AZD1981 will be assessed using the following outcome measures: incidence and severity of treatment-emergent adverse events and serious adverse events, clinical laboratory measures, and vital signs. In particular we will measure CBC's with differential at baseline and week 4 and liver function tests every 2 weeks based on past trial experience of dose-related toxicity.
Measured: 8 weeks
The Ability of AZD1981 to Inhibit Prostaglandin D2 (PGD2)-Induced Eosinophil Shape
The measure of Eosinophil shape change was assessed by cell scatter characteristics using a flow cytometer. Cellular scatter was established with buffer and then several doses of PGD2 stimulation.
Measured: Baseline, End of treatment, end of washout
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Idiopathic UrticariaStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Sarbjit S Saini, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02031679
- Sponsor's protocol ID
- NA_00089252
- Status last verified
- Jun 2017
- First submitted
- 7 Jan 2014
- Last updated
- 12 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa, Randomized, Placebo-controlled, Double-blind Study to Assess the Efficacy and Safety of the CRTh2 Antagonist AZD1981 in Patients With Chronic Idiopathic Urticaria (CIU) Who Are Refractory to H1 Antihistamines
- ClinicalTrials.gov ID
- NCT02031679
- Acronym / sponsor ID
- NA_00089252
- Conditions
- Chronic Idiopathic Urticaria
- Keywords
- Chronic Idiopathic Urticaria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Jan 2014 (actual)
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 9 Jan 2014 (estimated)
- Results
- Posted 12 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators are recruiting for a chronic hives study. This research is being done to test whether an investigational drug called AstraZeneca drug (AZD)1981 may be helpful for treating people with Chronic Idiopathic Urticaria who continue to have symptoms despite taking antihistamines. The word "investigational" means that AZD1981 is not approved for marketing by the Food and Drug Administration (FDA). The FDA is allowing the use of AZD1981 in this study.
People with chronic hives lasting for at least 6 months and without a known cause may join. The study involves 6 visits over 8 weeks. Approximately 48 participants expected to take part in this study at the Johns Hopkins Asthma and Allergy Clinic. All participants will be treated with the study medication and/or placebo for 8 weeks.
The results of this trial may have a benefit others with Chronic Idiopathic Urticaria who don't respond well to antihistamines by generating experience and data to support the design of a larger, multicenter trial investigating the efficacy of AZD1981 in treating antihistamine refractory CIU.
Detailed description
The investigators propose to use AZD1981 in subjects with chronic idiopathic urticaria (CIU) who are otherwise uncontrolled on first-line, oral antihistamine therapy. The skin lesion pathology in CIU shows a perivascular infiltrate of lymphocytes (both Th2 and Th1), eosinophils, and basophils, and closely resembles an allergen-induced late-phase reaction. Further, murine studies show that the chemoattractant receptor-homologous molecule expressed on Th2 (CRTh2) pathway is important in leukocyte recruitment following allergen challenge of the skin. Our proposed hypothesis is that AZD1981 in CIU will reduce CRTh2-expressing, leukocyte recruitment to the skin and reduce leukocyte activation through CRTh2, thus reducing the signs and symptoms in CIU refractory to control with antihistamines.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD1981 | Experimental | Drug: AZD1981AZD1981 for oral administration will be available in tablet form. AZD1981 tablets will be provided in 10 mg strengths. The drug will be self-administered by the subject. Subjects will take 4 tablets in the morning, 4 tablets in the afternoon, and 4 tablets in the evening. The tablets should be swallowed whole with a glass of water. |
| Placebo | Placebo comparator | Drug: PlaceboThe placebo will be available in tablet form. The placebo contains the same ingredients as the AZD1981 with the exception of the active compound. The placebo will be self-administered by the subject. Subjects will take 4 tablets in the morning, 4 tablets in the afternoon, and 4 tablets in the evening. The tablets should be swallowed whole with a glass of water. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Females must be surgically sterile or postmenopausal or using a highly effective form of birth control throughout the duration of the study
- Females must have a negative urine pregnancy test at screening
- Must meet the criteria for Chronic Idiopathic Urticaria (CIU) as defined by itching and hives for >3 days per week for over 6 weeks with no clear cause
- CIU symptoms must have started at least 6 months prior to starting the study
- Must have moderate to severe CIU, using a standardized survey, despite taking antihistamines
Key exclusion criteria (10 listed)
- Pregnant females or females who plan to become pregnant during the study
- Drug or alcohol abuse within the past 3 years
- Use of any investigational drug with 30 days of the start of the study
- Eczema or other skin conditions associated with itching (besides hives)
- Inability to comply with follow-up procedures
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 |
|---|---|---|
| AZD1981Also: Oral CRTh2 antagonistAZD1981 is an oral, potent, selective, reversible antagonist of CRTh2 (Chemoattractant Receptor Homologous Molecule expressed on Th2 cells). | Drug | AZD1981 |
| PlaceboSugar pill manufactured to mimic AZD1981 10 mg tablet | Drug | Placebo |
Primary outcome
The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7)
Time frame: 7 Days
The UAS score, which is the sum of pruritus and hives, will be used to calculate the UAS7. UAS is a validated measure of Chronic Spontaneous Urticaria (CSU) disease activity which scores the intensity of pruritus (0-3, with 0 = no itch and 3 is severe itch) and number of hives (0-3 0 means no hives and 3 means greater than 50 hives) with a maximum value of 6 for a given day. The UAS7 is the sum of the daily average UAS scores (average of a.m. and p.m.) for 7 days with a minimum score of 0 and a maximum value of 42. The UAS7 is a sum of the daily average (average of a.m. and p.m.) for 7 days. The baseline score was established during the second placebo therapy week and compared to the final week of the 4 week active treatment period.
2 secondary outcomes
The Number of Participants With Adverse Events
Time frame: 8 weeks
The Ability of AZD1981 to Inhibit Prostaglandin D2 (PGD2)-Induced Eosinophil Shape
Time frame: Baseline, End of treatment, end of washout
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Sarbjit S Saini, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD1981 in people with Chronic Idiopathic Urticaria, run by Johns Hopkins University at 1 site in United States.
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 10 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 12 Jul 2017. 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 States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7) (time frame: 7 Days). 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 12 Jul 2017.