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Old 01-17-2020, 02:51 PM
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Dave @ ActiveMSers
 
Join Date: Jun 2008
Location: Albuquerque, NM
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There are strict inclusion and exclusion criteria. And even if you are selected, there is a 50/50 chance you will be randomized into BAT (best available treatment): natalizumab, alemtuzumab, ocrelizumab, or rituximab. As a Phase 3, this is a critical trial to finally get FDA approval. -D

Criteria....

Ages Eligible for Study: 18 Years to 55 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No

Inclusion Criteria:

Participant(s) must meet all of the following criteria to be eligible for this study:

Diagnosis of Multiple Sclerosis (MS) according to the 2017 McDonald Criteria
(Kurtzke) Expanded Disability Status Scale (EDSS) ≥ 2.0 and ≤ 5.5 at the time of randomization (Day 0)
T2 abnormalities on brain Magnetic Resonance Imaging (MRI) that fulfill the 2017 McDonald MRI criteria for dissemination in space

--A detailed MRI report or MRI images must be available for review by the site neurology investigator.

Highly active treatment-resistant relapsing MS, defined as ≥ 2 episodes of treatment failure in the 24 months prior to the screening visit (Visit -2). as described below:

Each episode of treatment failure must occur following ≥ 3 months of treatment with an FDA-approved Disease-modifying Therapy (DMT) for relapsing forms of MS, or with rituximab, and
At least one episode of treatment failure must occur with an oral agent or a monoclonal antibody, specifically: dimethyl fumarate (Tecfidera®), teriflunomide (Aubagio®), cladribine (Mavenclad®), daclizumab (Zinbryta®), siponimod (Mayzent®), fingolimod (Gilenya®), rituximab (Rituxan®), ocrelizumab (Ocrevus®), natalizumab (Tysabri®), or alemtuzumab (Campath®, Lemtrada®), and
At least one episode of treatment failure must have occurred within the 12 months prior to the screening visit (Visit -2), and
At least one episode of treatment failure must be a clinical MS relapse (see item d.i. below). The other episode(s) must occur at least one month before or after the onset of the clinical MS relapse, and must be either another clinical
MS relapse or MRI evidence of disease activity (see item d.ii. below):

i. Clinical MS relapse must be confirmed by a neurologist's assessment and documented contemporaneously in the medical record. If the clinical MS relapse is not documented in the medical record, it must be approved by the study adjudication committee, and

ii. MRI evidence of disease activity must include ≥ 2 unique active lesions on a brain or spinal cord MRI. A detailed MRI report or MRI images must be available for review by the site neurology investigator. A unique active lesion is defined as either of the following:

A gadolinium-enhancing lesion, or
A new non-enhancing T2 lesion compared to a reference scan obtained not more than 24 months prior to the screening visit (Visit -2).
Candidacy for treatment with at least one of the following high efficacy DMTs: natalizumab, alemtuzumab, ocrelizumab, and/or rituximab.

--Note: Rituximab and ocrelizumab are considered equivalent for candidacy.Candidacy for treatment for each DMT is defined as meeting all of the following:

No prior treatment failure with the candidate DMT, and
No contraindication to the candidate DMT, and
No treatment with the candidate DMT in the 12 months prior to screening.
Insurance or public funding approval for MS treatment with at least one candidate DMT, and
Ability to comply with study procedures and provide informed consent, in the opinion of the investigator.

---------------

Exclusion Criteria:

Subject(s) who meet any of the following criteria will not be eligible for this study:

Diagnosis of primary progressive Multiple Sclerosis (MS) according to the 2017 McDonald criteria
History of neuromyelitis optica or anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies associated encephalomyelitis
Prior treatment with an investigational agent within 3 months or 5 half-lives, whichever is longer
Either of the following within one month prior to randomization (Day 0):

Onset of acute MS relapse, or
Treatment with intravenous methylprednisolone 1000 mg/day for 3 days or equivalent.
Initiation of natalizumab, alemtuzumab, ocrelizumab, or rituximab between screening visit (Visit -2) and randomization (Day 0)
Brain MRI or Cerebrospinal fluid (CSF) examination indicating a diagnosis of progressive multifocal leukoencephalopathy (PML)
History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS)
Presence of unexplained cytopenia, polycythemia, thrombocythemia or leukocytosis
History of sickle cell anemia or other hemoglobinopathy
Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C

-Note: Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection.

Presence or history of mild to severe cirrhosis
Hepatic disease with the presence of either of the following:

Total bilirubin ≥ 1.5 times the upper limit of normal (ULN) or total bilirubin

3.0 times the ULN in the presence of Gilbert's syndrome, or
Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2.0 times the ULN.
Evidence of HIV infection
Positive QuantiFERON - TB Gold or TB Gold Plus test results (e.g., blood test results that detect infection with Mycobacterium tuberculosis) Note: A Purified Protein Derivative (PPD) tuberculin test may be substituted for QuantiFERON - TB Gold or TB Gold Plus test.
Active viral, bacterial, endoparasitic, or opportunistic infections
Active invasive fungal infection
Hospitalization for treatment of infections or parenteral (IV or IM) antibacterials, antivirals, antifungals, or antiparasitic agents within the 30 days prior to randomization (Day 0) unless clearance is obtained from an Infectious Disease specialist
Receipt of live or live-attenuated vaccines within 6 weeks of randomization (Day 0)
Presence or history of clinically significant cardiac disease including:

Arrhythmia requiring treatment with any antiarrhythmia therapy, with the exception of low dose beta blocker for intermittent premature ventricular contractions
Coronary artery disease with a documented diagnosis of either:

Chronic exertional angina, or
Signs or symptoms of congestive heart failure.
Evidence of heart valve disease, including any of the following:

Moderate to severe valve stenosis or insufficiency,
Symptomatic mitral valve prolapse, or
Presence of prosthetic mitral or aortic valve.
Left ventricular ejection fraction (LVEF) < 50%
Impaired renal function defined as Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
Forced expiratory volume in one second (FEV1) <70% predicted (no bronchodilator)
Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb) < 70% predicted
Poorly controlled diabetes mellitus, defined as HbA1c >8%
History of malignancy, with the exception of adequately treated localized basal cell or squamous skin cancer, or carcinoma in situ of the cervix.

-Note:Malignancies for which the participant is judged to be cured by therapy completed at least 5 years prior to randomization (Day 0) will be considered on an individual basis by the study adjudication committee.

Presence or history of any moderate to severe rheumatologic autoimmune disease requiring treatment, including but not limited to the following:

systemic lupus erythematous
systemic sclerosis
rheumatoid arthritis
Sjögren's syndrome
polymyositis
dermatomyositis
mixed connective tissue disease
polymyalgia rheumatica
polychondritis
sarcoidosis
vasculitis syndromes, or
unspecified collagen vascular disease.
Presence of active peptic ulcer disease, defined as endoscopic or radiologic diagnosis of gastric or duodenal ulcer
Prior history of AHSCT
Prior history of solid organ transplantation
Positive pregnancy test or breast-feeding
Inability or unwillingness to use effective means of birth control
Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
Psychiatric illness, mental deficiency, or cognitive dysfunction severe enough to interfere with compliance or informed consent
History of hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins
Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI with gadolinium administration
Presence or history of ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage
Presence or history of other neurological disorders, including but not limited to:

central nervous system (CNS) or spinal cord tumor
metabolic or infectious cause of myelopathy
genetically-inherited progressive CNS disorder
CNS sarcoidosis, or
systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments.
Presence of any medical comorbidity that the investigator determines will significantly increase the risk of treatment mortality, or
Presence of any other concomitant medical condition that the investigator deems incompatible with trial participation.
__________________
Dave Bexfield
ActiveMSers
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