Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis

NCT02228213 | Completed Phase 2 DMC

• 2 other identifiers: MIS416-202U1111-1166-0910
• Study Type: interventional
• Target: 93
• Locations: 2 countries
• Sites: 7

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.

Conditions

Secondary Progressive Multiple Sclerosis

Keywords

multiple sclerosis; SPMS

Outcome Measures

Primary Outcomes (2)

• 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);

  Baseline, 3, 6, 9 and 12 months

• 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.

  Up to 12 months

Secondary Outcomes (5)

• Change from baseline of disability and health status at 12 months

  Baseline, 3, 6, 9, and 12 months

• Change from baseline of neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers at 12 months

  Baseline, 3, and 12 months

• Change from baseline of activity of immune biomarkers in serum

  Up to 1 year

• Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF)

  Up to 12 months

• Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers

  Up to 12 months

Study Arms (2)

Treatment

EXPERIMENTAL

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

Biological: MIS416

Saline

PLACEBO COMPARATOR

Saline administered i.v. once weekly for 52 weeks

Drug: Saline

Interventions

MIS416 BIOLOGICAL

Intravenous administration weekly for 52 weeks

Treatment

Saline DRUG

Intravenous administration weekly for 52 weeks

Also known as: Placebo

Saline

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A historical or current cranial MRI scan demonstrating T2-hyperintense lesions consistent with MS.
• Has SPMS as determined by the 2010 Update to the McDonald Criteria
• An Expanded Disability Status Scale (EDSS) of 3.0 to 6.5 at Screening.
• Has SPMS which, in the judgment of the investigator, has been clinically active and functionally progressive within the 2 years prior to Screening
• The absence of MS relapse for at least two years prior to Baseline.
• Neurologically stable for at least four weeks prior to Screening.
• 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.
• Provided written informed consent to participate.

You may not qualify if:

• Has primary Progressive MS (PPMS), Relapsing Remitting (RRMS), or progressive relapsing MS as determined by the 2010 update to the McDonald Criteria.
• Has not completed the discontinuation period for approved and/or investigational multiple sclerosis disease modifying therapies prior to screening.
• 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.
• Any previous exposure to investigational MS therapeutic vaccines.
• Any use of cell-depleting monoclonal antibodies including, but not limited to, Rituximab, or Ocrelizumab.
• 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.
• Contraindication to MRI (e.g., pacemaker or other contraindicated implanted metal device, allergy to gadolinium, or unmanageable claustrophobia).
• A history of alcohol or drug abuse (including cannabinoid use) within two years prior to Screening.
• Has had major surgery or radiation therapy within four weeks prior to Screening.
• Has an active infection requiring antibiotics within two weeks prior to Screening.
• Has had active malignancy within two years of Screening, with the exception of basal cell carcinoma and squamous cell carcinoma of the skin.
• Uncontrolled congestive heart failure, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack within twelve weeks prior to Screening.
• Has angina, other symptomatic coronary artery disease, or known cardiomyopathy.
• Has symptomatic cardiac dysrhythmias requiring treatment, or persistent prolongation of the QTcF (Fredericia) interval to \> 450 msec for males or \> 470 msec for females.

Sponsors & Collaborators

• Innate Immunotherapeutics: lead
• Syneos Health: collaborator

Study Sites (7)

The Wesley-St. Andrew's Research Institute

Brisbane, Queensland, 4066, Australia

Location

PARC Clinical Research

Adelaide, South Australia, 5000, Australia

Location

Nucleus Network - Centre for Clinical Studies

Melbourne, Victoria, 3004, Australia

Location

Western Australian Neuroscience Research Institute

Perth, Western Australia, 6009, Australia

Location

Neurodegenerative Disorders Research

West Perth, Western Australia, 6005, Australia

Location

Optimal Clinical Trials

Auckland, 1010, New Zealand

Location

P3 Research

Wellington, 6021, New Zealand

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Interventions

MIS416 vaccine; Sodium Chloride

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Michael Silverman

  Innate Immunotherapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2014
• First Posted: August 28, 2014
• Study Start: October 1, 2014
• Primary Completion: May 1, 2017
• Study Completion: June 1, 2017
• Last Updated: July 14, 2017

Record last verified: 2017-07

Locations

AU (5); NZ (2)