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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02228213




Registration number
NCT02228213
Ethics application status
Date submitted
21/08/2014
Date registered
28/08/2014
Date last updated
14/07/2017

Titles & IDs
Public title
Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis
Scientific title
A Phase 2B Randomised, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of MIS416 in the Treatment of Subjects With Secondary Progressive Multiple Sclerosis
Secondary ID [1] 0 0
U1111-1166-0910
Secondary ID [2] 0 0
MIS416-202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Secondary Progressive Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MIS416
Treatment: Drugs - Saline

Experimental: Treatment - 500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks

Placebo Comparator: Saline - Saline administered i.v. once weekly for 52 weeks


Other interventions: MIS416
Intravenous administration weekly for 52 weeks

Treatment: Drugs: Saline
Intravenous administration weekly for 52 weeks

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline of neuromuscular function at 12 months - Neuromuscular function will be assessed using the following test:
MS Function Composite (MSFC), comprising the; timed 25 Foot Walk, 9 Hole Peg Test (9HPT), and Paced Auditory Serial Addition Test (PASAT);
Jebsen Hand Function Test (JHFT);
Grip, tip and key pinch strength;
Symbol digit modalities test (SDMT);
Sloan low-contrast letter visual acuity (SLCVA);
6-minute walk test (6MWT);
Timepoint [1] 0 0
Baseline, 3, 6, 9 and 12 months
Primary outcome [2] 0 0
Proportion of Participants with Serious and Non-Serious Adverse Events - Safety assessments will be conducted at each study visit and include; characterization of the type, incidence, severity, timing, seriousness, and relationship to treatment of adverse events (AEs); effects on vital signs and clinical laboratory parameters; changes on electrocardiograms (ECGs); and at 3 months and 12 months - the number of gadolinium-enhancing lesions on cranial MRI assessments.
Timepoint [2] 0 0
Up to 12 months
Secondary outcome [1] 0 0
Change from baseline of disability and health status at 12 months - Disability and health status will be assessed using the following assessments and patient reported outcomes:
Expanded Disability Status Scale (EDSS)
Patient Reported Outcomes (PROs) including;
SF-36 and its components;
MS Impact Scale (MSIS-29);
Neurological Fatigue Index for MS (NFI-MS);
Brief Pain Inventory (BPI).
Timepoint [1] 0 0
Baseline, 3, 6, 9, and 12 months
Secondary outcome [2] 0 0
Change from baseline of neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers at 12 months - Disease activity and neurodegeneration will be assessing using Magnetic Resonance Imaging (MRI) markers including lesions, whole brain atrophy (WBA) and Magnetization Transfer Ratio (MTR).
Timepoint [2] 0 0
Baseline, 3, and 12 months
Secondary outcome [3] 0 0
Change from baseline of activity of immune biomarkers in serum - The effect on immune biomarkers will include the analysis of serum for some or all of the following markers: IP-10 (CXCL10), MCP-1 (CCL2), MIG (CXCL9), IL-8 (CXCL8), IFN?, Neopterin, IL-1RA, sTNF-R, IL-12/23, p40, CD62E (E-selectin), CD54 (ICAM-1), and CD106 (VCAM-1).
Timepoint [3] 0 0
Up to 1 year
Secondary outcome [4] 0 0
Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF) - The effect on immune biomarkers will include the analysis of CSF for some or all of the following markers: IP-10 (CXCL10), MCP-1 (CCL2), MIG (CXCL9), IL-8 (CXCL8), IFN?, Neopterin, IL-1RA, sTNF-R, IL-12/23, p40, CD62E (E-selectin), CD54 (ICAM-1), and CD106 (VCAM-1).
Timepoint [4] 0 0
Up to 12 months
Secondary outcome [5] 0 0
Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers - Some or all of these biomarkers may be assayed ex vivo: PBMC expression of mRNA encoding proteins involved in myeloid differentiation and immune regulatory function (e.g. VEGF, Arginine, INOS, IL-10, MMP9); PBMC myeloid subset production of IL-10, TGFß, IL-6, TNFa, IL-1ß, IFN?, IL-17, and GM-CSF in response to stimulation with LPS, LPS/IFN? or MIS416 ex vivo; and PBMC subset analysis of myeloid and dendritic cell subsets for immunoregulatory cell subset markers.
Timepoint [5] 0 0
Up to 12 months

Eligibility
Key inclusion criteria
1. A historical or current cranial MRI scan demonstrating T2-hyperintense lesions
consistent with MS.

2. Has SPMS as determined by the 2010 Update to the McDonald Criteria

3. An Expanded Disability Status Scale (EDSS) of 3.0 to 6.5 at Screening.

4. Has SPMS which, in the judgment of the investigator, has been clinically active and
functionally progressive within the 2 years prior to Screening

5. The absence of MS relapse for at least two years prior to Baseline.

6. Neurologically stable for at least four weeks prior to Screening.

7. Has the following laboratory values within three days prior to initiation of
Investigational Product:

- Absolute neutrophil count (ANC) >= 1 x 109/L;

- Platelet count >= 100 x 109/L;

- Serum creatinine =< 1.5 mg/dL;

- Aspartate aminotransferase (AST) =<2 × upper limit of normal;

- Alanine aminotransferase (ALT) =< 2 × upper limit of normal.

8. Provided written informed consent to participate.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has primary Progressive MS (PPMS), Relapsing Remitting (RRMS), or progressive
relapsing MS as determined by the 2010 update to the McDonald Criteria.

2. Has not completed the discontinuation period for approved and/or investigational
multiple sclerosis disease modifying therapies prior to screening.

3. Has had any other immunomodulatory drug therapy or immunosuppressive therapy within
four weeks prior to Screening, or systemic corticosteroids within the eight weeks
prior to Screening.

4. Any previous exposure to investigational MS therapeutic vaccines.

5. Any use of cell-depleting monoclonal antibodies including, but not limited to,
Rituximab, or Ocrelizumab.

6. A diagnosis or history of collagen vascular disease (including Sjögren's syndrome and
systemic lupus erythematosus), anticardiolipin antibody syndrome, cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukoencephalopathy, sarcoidosis,
vasculitis, Behcet's syndrome and/or Lyme disease.

7. Contraindication to MRI (e.g., pacemaker or other contraindicated implanted metal
device, allergy to gadolinium, or unmanageable claustrophobia).

8. A history of alcohol or drug abuse (including cannabinoid use) within two years prior
to Screening.

9. Has had major surgery or radiation therapy within four weeks prior to Screening.

10. Has an active infection requiring antibiotics within two weeks prior to Screening.

11. Has had active malignancy within two years of Screening, with the exception of basal
cell carcinoma and squamous cell carcinoma of the skin.

12. Uncontrolled congestive heart failure, myocardial infarction, cerebrovascular
accident, coronary/peripheral artery bypass graft surgery, or transient ischemic
attack within twelve weeks prior to Screening.

13. Has angina, other symptomatic coronary artery disease, or known cardiomyopathy.

14. Has symptomatic cardiac dysrhythmias requiring treatment, or persistent prolongation
of the QTcF (Fredericia) interval to > 450 msec for males or > 470 msec for females.

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)
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
The Wesley-St. Andrew's Research Institute - Brisbane
Recruitment hospital [2] 0 0
PARC Clinical Research - Adelaide
Recruitment hospital [3] 0 0
Nucleus Network - Centre for Clinical Studies - Melbourne
Recruitment hospital [4] 0 0
Western Australian Neuroscience Research Institute - Perth
Recruitment hospital [5] 0 0
Neurodegenerative Disorders Research - West Perth
Recruitment postcode(s) [1] 0 0
4066 - Brisbane
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment postcode(s) [5] 0 0
6005 - West Perth
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Innate Immunotherapeutics
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Syneos Health
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine whether MIS416 administered once weekly over 12
months is safe, tolerable, and improves a range of signs and symptoms associated with
secondary progressive multiple sclerosis.
Trial website
https://clinicaltrials.gov/show/NCT02228213
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Silverman
Address 0 0
Innate Immunotherapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications