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Trial registered on ANZCTR


Trial ID
ACTRN12613001096741
Ethics application status
Approved
Date submitted
27/06/2013
Date registered
1/10/2013
Date last updated
11/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized, placebo-controlled, double blind, parallel design study of Xolair (omalizumab) for the management of treatment-resistant systemic and cutaneous mastocytosis.
Scientific title
In patients with systemic and/or cutaneous mastocytosis, is omalizumab (Xolair) in addition to standard care more effective in the management of symptoms than standard care alone? A randomized, placebo-controlled, double blind, parallel design study
Secondary ID [1] 282671 0
Nil
Universal Trial Number (UTN)
U1111-1144-3330
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic mastocytosis
289368 0
Mastocytosis in the skin 289370 0
Condition category
Condition code
Blood 289764 289764 0 0
Other blood disorders
Skin 290615 290615 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Omalizumab (Xolair) 375mg subcutaneously every 4 weeks for 6 months

Trial medication with be administered in hospital
Intervention code [1] 287416 0
Treatment: Drugs
Comparator / control treatment
Placebo infusion subcutaneously every 4 weeks for 6 months.

The placebo is formulated by Novartis to resemble the trial medication ie a lyophilised sterile powder, containing 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate.
Control group
Placebo

Outcomes
Primary outcome [1] 289885 0
Improvement in AFIRMM score (standardised and validated symptom score for mastocytosis)
Timepoint [1] 289885 0

4 weeks after final dose (week 24)
Secondary outcome [1] 303477 0
Improvement in VAS (symptom score)
Timepoint [1] 303477 0

4 weeks after last dose (week 24)
Secondary outcome [2] 303478 0
Improvement in standardised clinical assessment for mastocytosis(SCORMA)
Timepoint [2] 303478 0

4 weeks after last dose (week 24)
Secondary outcome [3] 303479 0
Improvement in standardised score for clinical skin photography as assessed by a dermatologist
Timepoint [3] 303479 0

4 weeks after last dose (week 24)
Secondary outcome [4] 303480 0
Improvement in laboratory parameters relating to mastocytosis including tryptase, routine haematology and biochemistry, bone turnover markers, basophil activation and serum cytokines
Timepoint [4] 303480 0

4 weeks after last dose (week 24)

Eligibility
Key inclusion criteria
1. Over 18 years of age;
2. A diagnosis of Indolent Systemic Mastocytosis, OR
Smouldering Systemic Mastocytosis, OR
Aggressive Systemic Mastocytosis, OR
Cutaneous Mastocytosis as per WHO current guidelines, with satisfaction of Valent 2007 criteria for Mastocytosis in the Skin (Valent P, Akin C, Escribano L et. al. Standards and Standardization in Mastocytosis: Consensus Statements on Diagnosis, Treatment Recommendations and Response Criteria. Eur J Clin Invest 2007, 37 (6); 435 – 453.);
3. Breakthrough symptoms of disease despite maximal tolerated conventional therapy.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnancy (a beta-HCG and pregnancy counseling will be performed for all female patients of child-bearing age).
2. Terminal illness
3. Associated haematological clonal non-mast cell lineage disease or mast cell leukaemia
4. Beta blocker use
5. Unable to give consent
6. Known sensitivity to study drug(s) or class of study drug(s)
7. Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study (specify as required)
8. Use of any other investigational agent in the last 30 days

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by a separate group
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data will be analysed with the assistance of the RMH Clinical Epidemiology and Health Service Evaluation Unit (EpiCentre). Outcomes will be determined by measuring changes in the relevant parameters for each patient, with the patient and control groups compared by 2 tailed t test for each parameter. As the variables measured are not likely to be independent, a Bonferroni correction will not be applied.

Sample size: assuming a drop-out rate of 10%, to have an 80% chance of detecting a difference of 1 standard deviation of AFIRMM score improvement in the control group at 95% confidence (2-tailed), 38 patients would need to be enrolled in the study. A single standard deviation of the control group score has been selected as the minimal improvement likely to represent a clinical difference.

The continuous variables described above will be summarized with standard descriptive statistics including means, standard deviations, medians and ranges. Inferential analyses will be parametric except in the case of markedly non-normal distribution.

An alpha level of 0.05 will be used as a cut-off point for statistical significance, and all statistical tests will be 2 sided. Analysis will be intention-to-treat.
The assessment of safety will be based mainly on the frequency of adverse events, which includes all serious adverse events, at each time point. Adverse events will be summarized by presenting for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each body system and having each individual adverse event. Any other information collected (e.g. severity or relatedness to study medication) will be listed as appropriate.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1174 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 7021 0
3050 - Royal Melbourne Hospital

Funding & Sponsors
Funding source category [1] 287520 0
Commercial sector/Industry
Name [1] 287520 0
Novartis Pharmaceuticals, Australia
Address [1] 287520 0
Novartis Pharmaceuticals Australia Pty Ltd
54 Waterloo Road
NORTH RYDE. NSW. 2113
Country [1] 287520 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Novartis Pharmaceuticals Australia Pty Ltd
54 Waterloo Road
NORTH RYDE. NSW. 2113
Country
Australia
Secondary sponsor category [1] 286266 0
Hospital
Name [1] 286266 0
Royal Melbourne Hospital
Address [1] 286266 0
Grattan Street, Parkville VIC 3050
Country [1] 286266 0
Australia
Other collaborator category [1] 278223 0
Other Collaborative groups
Name [1] 278223 0
Walter and Eliza Hall Institute
Address [1] 278223 0
1G Royal Parade
Parkville VIC
3052
Country [1] 278223 0
Australia
Other collaborator category [2] 278224 0
University
Name [2] 278224 0
University of Melbourne
Address [2] 278224 0
Parkville VIC 3010
Country [2] 278224 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289497 0
Melbourne Health HREC
Ethics committee address [1] 289497 0
Grattan Street
Parkville, VIC 3050
Ethics committee country [1] 289497 0
Australia
Date submitted for ethics approval [1] 289497 0
Approval date [1] 289497 0
22/05/2013
Ethics approval number [1] 289497 0
2013.026
Ethics committee name [2] 291884 0
WEHI HREC
Ethics committee address [2] 291884 0
WEHI
1G Royal Parade
Parkville VIC 3052
Ethics committee country [2] 291884 0
Australia
Date submitted for ethics approval [2] 291884 0
15/10/2013
Approval date [2] 291884 0
16/10/2013
Ethics approval number [2] 291884 0
13/09
Ethics committee name [3] 298173 0
University of Melbourne Ethics Committee
Ethics committee address [3] 298173 0
Human Research Ethics
Research Ethics & Integrity
Research Innovation and Commercialisation
University of Melbourne
Level 12, 198 Berkeley Street
Carlton, VIC 3010 AUSTRALIA
Ethics committee country [3] 298173 0
Australia
Date submitted for ethics approval [3] 298173 0
10/12/2014
Approval date [3] 298173 0
13/02/2015
Ethics approval number [3] 298173 0
1443312

Summary
Brief summary
The study aims to assess the effect of omalizumab (Xolair) on systemic and cutaneous mastocytosis
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40594 0
Dr Jeremy McComish
Address 40594 0
Department of Immunology and Allergy
Royal Melbourne Hospital
Grattan Street
Parkville, VIC 3050
Country 40594 0
Australia
Phone 40594 0
+61 3 9342 7191
Fax 40594 0
Email 40594 0
jeremy.mccomish@mh.org.au
Contact person for public queries
Name 40595 0
Dr Jeremy McComish
Address 40595 0
Department of Immunology and Allergy
Royal Melbourne Hospital
Grattan Street
Parkville, VIC 3050
Country 40595 0
Australia
Phone 40595 0
+61 3 9342 7191
Fax 40595 0
Email 40595 0
jeremy.mccomish@mh.org.au
Contact person for scientific queries
Name 40596 0
Dr Jeremy McComish
Address 40596 0
Department of Immunology and Allergy
Royal Melbourne Hospital
Grattan Street
Parkville, VIC 3050
Country 40596 0
Australia
Phone 40596 0
+61 3 9342 7191
Fax 40596 0
Email 40596 0
jeremy.mccomish@mh.org.au