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Trial registered on ANZCTR


Registration number
ACTRN12618000534280
Ethics application status
Approved
Date submitted
5/04/2018
Date registered
10/04/2018
Date last updated
10/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to Assess the Efficacy and Safety of Tecfidera in Patients with Amyotrophic Lateral Sclerosis - TEALS Study
Scientific title
Phase 2 Randomised Placebo Controlled Double Blind Study to Assess the Efficacy and Safety of Tecfidera in Patients with Amyotrophic Lateral Sclerosis (TEALS Study)
Secondary ID [1] 294497 0
Nil Known
Universal Trial Number (UTN)
U1111-1211-7805
Trial acronym
TEALS study
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 307269 0
Condition category
Condition code
Neurological 306388 306388 0 0
Neurodegenerative diseases
Musculoskeletal 306412 306412 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The TEALS study is assessing the effects of Dimethyl Fumarate (trade name tecfidera ) in Amyotrophic Lateral Sclerosis. The dosage is 240 mg twice daily for a period of 36 weeks. Mode of administration is an oral tablet. Adherence to intervention will be drug tablet return.
Intervention code [1] 300794 0
Treatment: Drugs
Comparator / control treatment
The placebo is a micro crystalline cellulose capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 305395 0
The primary outcome for this study is Amyotrophic Lateral Sclerosis progression determined using the ALS functional Rating Scale-revised.
Timepoint [1] 305395 0
Timepoints for the primary outcome will be assessed at screening, week 0, week 12, week 24, week 36 and 40 weeks.
Secondary outcome [1] 345064 0
1. Survival status at 40 weeks. Assessed form hospital records


Timepoint [1] 345064 0
Time-points for the secondary outcome will be assessed at 40 weeks.
Secondary outcome [2] 345168 0
2. Change in lower motor dysfunction as measured by:
-Higher Neurophysiological Index (NPI) and Split Hand Index (SI).
-Improved muscle strength, as measured by power grip dynamometry and Medical Research Council (MRC) Score.

This is a composite outcome measure.
Timepoint [2] 345168 0
Timepoints for the secondary outcome will be assessed at 40 weeks.
Secondary outcome [3] 345169 0
3. Change in respiratory function as measured by:
-Forced vital capacity (FVC).
-Sniff nasal inspiratory pressure (SNIP).
Composite outcome measure.
Timepoint [3] 345169 0
Timepoints for the secondary outcome will be assessed at 40 weeks.
Secondary outcome [4] 345170 0
4. Change in urinary neurotrophin receptor P75 levels.
Timepoint [4] 345170 0
Timepoints for the secondary outcome will be assessed at screening, week 12, week 24, week 36 and 40 weeks.
Secondary outcome [5] 345171 0
5. Change in clinical scores will be measured using the ALS Specific Quality of Life-Revised (ALSSQOL-R) questionnaire
Timepoint [5] 345171 0
Timepoints for the secondary outcome will be assessed at 40 weeks.

Eligibility
Key inclusion criteria
1. Male and female patients aged 18 to 85 years at the time of the Screening Visit.
2. Able to provide informed consent and comply with study procedures.
3. Sporadic ALS diagnosed as definite, probable, or possible according to the Awaji criteria as determined by a neurologist subspecializing in ALS.
4. Disease duration at recruitment less than 24 months from diagnosis.
5. Patient must have the results of magnetic resonance imaging scan of brain and spinal cord undergone within 2 years (24 months) prior to the Screening Visit.
6. Forced vital capacity >60% of predicted value as adjusted for gender, height, and age at the Screening Visit.
7. Must be on a stable dose of riluzole for at least 30 days prior to the Screening Visit.
8. Patient who has established care with a neurologist at 1 of the 5 specialised ALS clinics involved in the study and will maintain this clinical care throughout the study.
9. If a patient is referred from a third party (neurologist or a State based ALS organisation) they should be willing to transfer care to the neurologist participating in the study.
10. Patients may participate in clinical registries, but will be excluded if they are participating in a clinical study involving an alternative investigational treatment.
11. Women of childbearing potential must have a negative urine pregnancy test at screening and Baseline, and be surgically sterile or postmenopausal, or using highly effective methods of contraception throughout the study and for 30 days after the last dose of IP.
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Dependence on mechanical ventilation at the time of screening.
2. Gastrostomy at the time of Screening/Baseline Visit. If the patient has a gastrostomy tube inserted post randomisation they will be allowed to continue in the study.
3. Participation in any other IP study or using an IP (within 12 weeks prior to screening).
4. Known hypersensitivity to Tecfidera or any excipients in this product.
5. Presence of a monogenic cause of ALS (e.g. known mutation in superoxide dismutase-1 (SOD1), expansion in c9orf72 etc.).
6. Taking immunosuppressive medications.
7. Positive test for human immunodeficiency virus (HIV), hepatitis B (+HbsAg), or hepatitis C.
8. Presence of any of the following clinical conditions at the time of screening:
-Unstable medical disease (such as unstable angina, heart failure, chronic obstructive pulmonary disease, liver disease or renal disease), or active infectious diseases (such as hepatitis B or C or tuberculosis), or current malignancy.
-Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the Screening Visit. This exclusion criteria is based on a prior psychiatric diagnosis that is unstable as determined by the patient’s treating Psychiatrist.
-Dementia as previously diagnosed by a medical practitioner.

9. Safety Laboratory Criteria at the Screening Visit:
-Alanine aminotransferase >3 × the upper limit of normal (ULN).
-Total bilirubin, lactate, triglycerides, amylase, or lipase >2 × the ULN.
-Patient has impaired renal function defined as creatinine clearance of <40 mL/min via Cockroft Gault method.
-Absolute neutrophil count of <2 × 109/L.
-Absolute lymphocyte count of <0.5 × 109/L.
-Platelet concentration of <100 × 109/L.
-Haemoglobin <100 g/L.

10. Female patients who are pregnant or lactating, or intend to become pregnant during the study period.

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 computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation). This will be overseen by IQUVIA (CRO) and Cenduit.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Nil
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The calculation of the sample size was based on the following criteria: (i) mean difference of 7 points in the ALSFRS-R between active and control groups at 9 months; (ii) common standard deviation (SD) of 8%; (iii) a value of 0.05; (iv) power 0.9; (v) active:control group (m-value) 2:1; and (vi) 20% dropout rate assumed for both groups.

Based on previous clinical studies and literature; it is assumed that the mean difference is 7 and common SD is 8% in the ALSFRS-R between active and control groups. A clinically important response rate on Tecfidera is defined as 0.9. A 2:1 (Dimethyl Fumarate:Placebo) allocation, 90% power and 5% statistical significance rate estimate 48:24 evaluable patients will be required for this study. With a 20% estimated non-evaluable rate, it is planned to assign 90 patients (60:30) to randomised treatment.

Recruitment
Recruitment status
Not yet recruiting
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)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 10553 0
Westmead Hospital - Westmead
Recruitment hospital [2] 10554 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 10555 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [4] 10556 0
Calvary Health Care Bethlehem Ltd - Caulfield
Recruitment hospital [5] 10557 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 10558 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 22272 0
2145 - Westmead
Recruitment postcode(s) [2] 22273 0
2050 - Camperdown
Recruitment postcode(s) [3] 22274 0
4029 - Herston
Recruitment postcode(s) [4] 22275 0
3162 - Caulfield
Recruitment postcode(s) [5] 22276 0
5042 - Bedford Park
Recruitment postcode(s) [6] 22277 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 299121 0
Other
Name [1] 299121 0
FightMND
Address [1] 299121 0
Address: c/o AFL House, 140 Harbour Esplanade, Docklands, Vic 3008
Postal Address: PO Box 23390, Docklands, Vic, 8012
Country [1] 299121 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 298381 0
None
Name [1] 298381 0
Address [1] 298381 0
Country [1] 298381 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300055 0
Westmead Area Local Health District
Ethics committee address [1] 300055 0
Research Office, Level 2, REN Building
Westmead Hospital, Hawkesbury & Darcy Roads, Westmead NSW 2145
Ethics committee country [1] 300055 0
Australia
Date submitted for ethics approval [1] 300055 0
16/08/2017
Approval date [1] 300055 0
11/10/2017
Ethics approval number [1] 300055 0
AU RED HREC/17/WMEAD/353

Summary
Brief summary
The primary purpose of this study is to assess whether dimethyl fumarate will slow down disease progression in sporadic ALS. The study hypothesis is based on findings that the regulatory T cells, which form an important component of the immune system, slow down disease progression in ALS. increasing the levels and function of regulatory T cells could slow down disease progression in ALS. Dimethyl fumarate effectively increases the function of regulatory T cells and it is hoped that this increase in T cell function will significantly slow disease progression in ALS when compared to conventional treatment.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes
Nil

Contacts
Principal investigator
Name 82410 0
Prof Steve Vucic
Address 82410 0
Department of Neurology
Westmead Hospital
Cnr Hawkesbury and Darcy Roads
Westmead NSW 2145
Country 82410 0
Australia
Phone 82410 0
+61298456097
Fax 82410 0
Email 82410 0
steve.vucic@sydney.edu.au
Contact person for public queries
Name 82411 0
Prof Steve Vucic
Address 82411 0
Department of Neurology
Westmead Hospital
Cnr Hawkesbury and Darcy Roads
Westmead NSW 2145
Country 82411 0
Australia
Phone 82411 0
+61298456097
Fax 82411 0
Email 82411 0
steve.vucic@sydney.edu.au
Contact person for scientific queries
Name 82412 0
Prof Steve Vucic
Address 82412 0
Department of Neurology
Westmead Hospital
Cnr Hawkesbury and Darcy Roads
Westmead NSW 2145
Country 82412 0
Australia
Phone 82412 0
+61298456097
Fax 82412 0
Email 82412 0
steve.vucic@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
No Results