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Trial registered on ANZCTR


Registration number
ACTRN12611001092987
Ethics application status
Approved
Date submitted
19/10/2011
Date registered
20/10/2011
Date last updated
10/08/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of EMA401 and biomarkers in the treatment of pain due to nerve damage following chemotherapy.
Scientific title
A Phase 2 open label biomarker study of angiotensin II type 2 receptor antagonist EMA401 for the treatment of pain in patients with chemotherapy-induced peripheral neuropathy.
Secondary ID [1] 273221 0
Protocol number EMA401-005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chemotherapy induced peripheral neuropathy 278983 0
Condition category
Condition code
Neurological 279159 279159 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EMA401 100mg orally twice a day for 28 days
Intervention code [1] 269553 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 279801 0
To determine the efficacy of EMA401 100 mg orally twice daily for 28 days, in reducing spontaneous neuropathic pain, from baseline to Week 4 of treatment, in patients with chemotherapy-induced peripheral neuropathy.

This will be assessed using patient pain scores (on a scale of 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine).
Timepoint [1] 279801 0
After 28 days treatment.
Secondary outcome [1] 294476 0
To evaluate the efficacy of EMA401 100 mg orally twice daily for 28 days in restoring nerve fibre phenotype in skin punch biopsies.

This will be assessed by examing changes in biomarkers on slides taken from biopsy samples pre and post treatment.
Timepoint [1] 294476 0
After 28 days treatment
Secondary outcome [2] 294477 0
To evaluate the efficacy of EMA401 100 mg orally twice daily for 28 days in reducing evoked pain in patients with chemotherapy-induced peripheral neuropathy.

This will be assessed by change in area of evoked pain from using brush, monofilaments, pin prick, thermal thresholds, and contact heat evoked potentials (CHEPS), patient pain scores, patient ratings of change, and the Short Form - McGill Pain Questionnaire (SF-MPQ-2)
Timepoint [2] 294477 0
After 28 days treatment
Secondary outcome [3] 294478 0
To evaluate the safety and tolerability of EMA401 100 mg orally twice daily for 28 days in patients with chemotherapy-induced peripheral neuropathy.

This will be assessed by incidence and severity of adverse events, and changes and findings in laboratory parameters, physical and neurological examinations, vital signs, and ECG. All adverse events that occur will be measured by recording details of the event including description, start and stop dates, severity, seriousness, and relationship to study drug
Timepoint [3] 294478 0
After 28 days treatment

Eligibility
Key inclusion criteria
Able to give voluntary written informed consent to participate in the study.

18 to 80 years old inclusive.

Previously received taxane and/or platinum based chemotherapy for any type of cancer and are not expected to receive further chemotherapy for the study duration.

Signs and symptoms of sensory peripheral neuropathy of the lower limbs which have been clinically stable for at least 8 weeks prior to Screening.

History of spontaneous pain in the lower limbs for at least 8 weeks prior to Screening.

Moderate to severe spontaneous neuropathic pain in the lower limbs.

Female of non-child-bearing potential, or if of child-bearing potential, must have used adequate contraceptive precautions for 30 days prior to Screening, and must agree to use two approved methods of contraception for the duration of the study and for one month after administration of the last dose of study medication
OR
Are male and agree to use two approved methods of contraception for the duration of the study and until one month after administration of the last dose of the study medication.

Able to read and understand English.

Have a telephone.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnant or breast-feeding.

Do not and cannot comply with the protocol concomitant medication restrictions.

Participated in an investigational medical product study within the past 3 months prior to Day 1.

Exposure to more than 3 new chemical entities within 12 months prior to Day 1.

Previously received EMA401.

Known to be allergic to EMA401 or any of the excipients.

History or evidence of any other clinical neuropathy.

Any other pain condition or injury that may confound the self-evaluation of pain due to peripheral neuropathy.

History of clinically significant cardiac arrhythmias or the presence of clinically significant abnormalities on electrocardiogram (ECG) at screening.

Resting supine blood pressure < 165/95mmHg.

Resting pulse rate >100 or <50 beats per minute (bpm) on two consecutive measurements at least 10 minutes apart.
Calculated creatinine clearance (using Cockroft and Gault formula) of less than 50 mL/min at Screening.

Serum aspartate transaminase (AST), gamma glutamyl transaminase (GGT) or alanine transaminase (ALT) levels greater than 3.0 x the upper limit of normal or have total bilirubin concentrations greater than 2.0 x the upper limit of normal at Screening.

History of or current hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV) infection.

Other than the condition under study, have a history of or current active medical condition including allergic, skin, cardiovascular, psychiatric disease, drug or alcohol abuse, or laboratory finding, that in the opinion of the investigator precludes participation in the study, or may interfere with the study objectives / results.

Pacemaker or implanted brain or cord stimulators.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

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 outside Australia
Country [1] 3912 0
United Kingdom
State/province [1] 3912 0

Funding & Sponsors
Funding source category [1] 270047 0
Commercial sector/Industry
Name [1] 270047 0
Spinifex Pharmaceuticals Pty Ltd
Address [1] 270047 0
Corporate One, Suite G5
84 Hotham St
Preston, VIC, 3072
Australia
Country [1] 270047 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Spinifex Pharmaceuticals Pty Ltd
Address
Corporate One, Suite G5
84 Hotham St
Preston, VIC, 3072
Australia
Country
Australia
Secondary sponsor category [1] 269017 0
None
Name [1] 269017 0
Address [1] 269017 0
Country [1] 269017 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 272004 0
London Bridge Committee of the National Research Ethics Service, National Research Authority, National Health Service
Ethics committee address [1] 272004 0
Research Ethics Committee (REC) Centre Charing Cross, Room 12, 4th Floor West, Charing Cross Hospital, London W6 8RF.
Ethics committee country [1] 272004 0
United Kingdom
Date submitted for ethics approval [1] 272004 0
01/11/2011
Approval date [1] 272004 0
06/02/2012
Ethics approval number [1] 272004 0
11/LO/2042

Summary
Brief summary
Peripheral neuropathy is caused by damage to nerves. Current therapy needs to be improved as a significant proportion of neuropathic pain patients don’t respond to current therapy and these treatments have dose-limiting side effects.

EMA401 is an angiotensin II type 2 (AT2) receptor antagonist, a class of molecules that offers an innovative approach to the treatment of neuropathic pain. EMA401 has shown efficacy in a number of relevant models and good human safety and pharmacokinetics in Phase 1 studies.

This study will look at whether EMA401 reduces pain in patients who have peripheral neuropathy caused by cancer chemotherapy drugs, whether it has an effect on biomarkers of pain, and whether it is well tolerated.
Trial website
Trial related presentations / publications
Not applicable
Public notes

Contacts
Principal investigator
Name 33275 0
Prof Praveen Anand
Address 33275 0
Hammersmith Hospital
Peripheral Neuropathy Unit
Du Cane Rd
London
W12 0NN
United Kingdom
Country 33275 0
United Kingdom
Phone 33275 0
+44 (0)20 3313 3319
Fax 33275 0
Email 33275 0
p.anand@imperial.ac.uk
Contact person for public queries
Name 16522 0
Dr Tom McCarthy
Address 16522 0
Corporate One, Suite G5
84 Hotham St
Preston, VIC, 3072
Australia
Country 16522 0
Australia
Phone 16522 0
+61 3 9863 6820
Fax 16522 0
Email 16522 0
tom.mccarthy@spinifexpharma.com.au
Contact person for scientific queries
Name 7450 0
Dr Tom McCarthy
Address 7450 0
Corporate One, Suite G5
84 Hotham St
Preston, VIC, 3072
Australia
Country 7450 0
Australia
Phone 7450 0
+61 3 9863 6820
Fax 7450 0
Email 7450 0
tom.mccarthy@spinifexpharma.com.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary