Cold Contact Urticaria
Conditions
Brief summary
Urticaria is a very frequent skin condition characterised by transient wheal and flare type skin reactions associated with severe pruritus. Cold contact urticaria (CCU) is a frequent form of physical urticaria that is characterized by the development of wheal and flare type skin reactions due to the release of histamine and other proinflammatory mast cell mediators following exposure of the skin to cold. Among all physical urticaria subtypes the frequency of CCU varies between 5.7% and 33.8% in different studies. Physical urticarias including CCU are known to severely impair the quality of life of affected patients. The treatment of choice in CCU, as well as in other inducible forms and spontaneous urticaria, are non-sedating H1 antihistamines. Recent data have shown that updosing of H1 blockers is significantly more effective in reducing symptoms in cold urticaria than standard-dose treatment. Thus, patients who cannot be sufficiently controlled with standard-dose antihistamines should receive high-dose H1 blockers up to 4 times the standard dose as recommended by the new international guidelines for the management of urticaria. Previous phase II studies in patients with chronic spontaneous urticaria have shown favorable results for the treatment with omalizumab (Xolair®). Proof-of-concept data from completed studies suggest that omalizumab improves urticaria in patients with chronic spontaneous urticaria who have failed treatment with H1 antihistamines as well as those who have failed treatment with a combination of H1 and H2 antihistamines and a leukotriene receptor antagonist. In addition, two case reports of patients with severe therapy refractory CCU treated with omalizumab reported a complete response with no urticarial symptoms after cold challenge. In summary, these data suggest that omalizumab may have a beneficial effect in the treatment of CCU.
Interventions
DRUGOmalizumab
150mg, s.c., every 4 weeks
DRUGPlacebo
Placebo, s.c., every 4 weeks
Sponsors
Novartis Pharmaceuticals
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adults (18 years or older) Informed consent signed and dated Able to read, understand and willing to sign the informed consent form and abide with study procedures Diagnosis of CCU lasting for at least 6 months Willing, committed and able to return for all clinic visits and complete all study-related procedures, including willingness to have SC injections administered by a qualified person In females of childbearing potential: Negative pregnancy test; females willing to use highly effective contraception (Pearl-Index \< 1). A woman will be considered not of childbearing potential if she is post-menopausal for greater than two years or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) No participation in other clinical trials 4 weeks before and after participation in this study
Exclusion criteria
Patients with acute urticaria Concurrent/ongoing treatment with immunosuppressives (e.g. systemic steroids, cyclosporine, methotrexate, dapsone or others) within 4 weeks or 5 half lives prior to day 0, whichever is longer Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial Significant concomitant illness that would adversely affect the subject's participation or evaluation in this study History of malignancies within five years prior to screening other than a successfully treated non-metastatic cutaneous, basal, or squamous cell carcinoma and/or in situ cancer Presence of clinically significant laboratory abnormalities Lactating females or pregnant females Subjects for whom there is concern about compliance with the protocol procedures Any medical condition which, in the opinion of the Investigator, would interfere with participation in the study or place the subject at risk History of substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) within the last 5 years that could limit the subject's ability to comply with study procedures Subjects who are detained officially or legally to an official institute Previous use of omalizumab within the last 6 months Intake of antihistamines or leukotriene antagonists within 7 days prior to visit 1 Intake of oral corticosteroids within 14 days prior to visit 1 Use of depot corticosteroids or chronic systemic corticosteroids within 21 days before beginning of the study Known hypersensitivity to any ingredients, including excipients (sucrose, histidine, polysorbate 20) of the study medication or drugs related to omalizumab (e.g.: monoclonal antibodies, polyclonal gammaglobulin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Critical Temperature Thresholds (CTT) From Baseline to Day 70 After Treatment With Omalizumab Compared to Placebo | day 70 | The primary efficacy outcome was the change in trigger thresholds from baseline to week ten using TempTest® to assess critical temperature thresholds in °C. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Abnormal Physical Examinations, Laboratory Assessments, Vital Signs, and Adverse Events | day 70 | This includes physical examination, routine safety laboratory assessments, vital signs and adverse event reporting |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab 150mg Omalizumab: 150mg, s.c., every 4 weeks | 10 |
| Omalizumab 300mg Omalizumab: 300mg, s.c., every 4 weeks | 9 |
| Placebo Placebo: Placebo, s.c., every 4 weeks | 12 |
| Total | 31 |
Baseline characteristics
| Characteristic | Omalizumab 150mg | Omalizumab 300mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 12 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 9 Participants | 12 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Germany | 10 participants | 9 participants | 12 participants | 31 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 9 Participants | 23 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 10 | 4 / 9 | 5 / 12 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 | 0 / 12 |
Outcome results
Primary
Change in Critical Temperature Thresholds (CTT) From Baseline to Day 70 After Treatment With Omalizumab Compared to Placebo
The primary efficacy outcome was the change in trigger thresholds from baseline to week ten using TempTest® to assess critical temperature thresholds in °C.
Time frame: day 70
Population: female and male
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omalizumab 150mg | Change in Critical Temperature Thresholds (CTT) From Baseline to Day 70 After Treatment With Omalizumab Compared to Placebo | -10.6 degree celcius | Standard Deviation 7.6 |
| Omalizumab 300mg | Change in Critical Temperature Thresholds (CTT) From Baseline to Day 70 After Treatment With Omalizumab Compared to Placebo | -10.4 degree celcius | Standard Deviation 9.4 |
| Placebo | Change in Critical Temperature Thresholds (CTT) From Baseline to Day 70 After Treatment With Omalizumab Compared to Placebo | -0.3 degree celcius | Standard Deviation 3.9 |
p-value: 0.001ANOVA
p-value: 0.01ANOVA
Secondary
Number of Participants With Abnormal Physical Examinations, Laboratory Assessments, Vital Signs, and Adverse Events
This includes physical examination, routine safety laboratory assessments, vital signs and adverse event reporting
Time frame: day 70
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omalizumab 150mg | Number of Participants With Abnormal Physical Examinations, Laboratory Assessments, Vital Signs, and Adverse Events | 7 participants |
| Omalizumab 300mg | Number of Participants With Abnormal Physical Examinations, Laboratory Assessments, Vital Signs, and Adverse Events | 7 participants |
| Placebo | Number of Participants With Abnormal Physical Examinations, Laboratory Assessments, Vital Signs, and Adverse Events | 9 participants |
p-value: 0.988Chi-squared