Inclusion Criteria:
1. Male or female between 21 and 65 years old, inclusive.
2. Must be capable of understanding and providing written informed consent, including
subject authorization under the health insurance portability and accountability act
(HIPPA), prior to any study related procedures that are not part of routine medical
care.
3. Has an EDSS score at the screening visit of 2.0 to 7.0 inclusive.
4. Have a diagnosis of clinically definite SPMS. (Lublin, 2014)
5. Are considered neurologically stable for > 30 days prior to both screening, baseline
and week 48.
6. Must be otherwise healthy without confounding diseases.
7. Subject has decided to pursue cladribine tablets as their disease modifying therapy
(DMT) of choice, and have signed a study specific informed consent form.
8. Must be willing and physically able to comply with all required protocol visits and
complete all assessments.
9. Must be willing to complete 2 years of routine clinic follow-ups after study
completion as per cladribine tablets FDA guidelines.
10. Must have read the FDA approved patient labeling (medication guide) and be counseled,
risk of teratogenicity, lactation, lymphopenia and other hematologic toxicity,
infections, liver injury, hypersensitivity, cardiac failure and treatment handling and
administration.
11. If female: must have a negative serum pregnancy test at screen and week 48 and a
negative urine pregnancy test at baseline. All females must agree to notify us
immediately if they have concern of possible pregnancy.
12. If female: be neither pregnant or breastfeeding, nor attempting to conceive AND. • Use a highly effective method of contraception throughout the entire duration of the
study and for 6 months (5 menstrual cycles) following completion of the last dose of
study medication. As it is currently unknown whether cladribine tablets may reduce the
effectiveness of systemically acting hormonal contraceptives, a barrier method of
contraception should be implemented for the duration of the study.
13. If Male: must be willing to use contraception to avoid contributing to pregnancies 6
months following the last dose of study medication.
Exclusion Criteria:
1. Subjects with a diagnosis of a sub-type of MS other than PMS active (clinically
definite SPMS)
2. Have MRI findings other than MS that are considered significant per the P.I.
3. Have a clinical condition or medical history noted as a contraindication as per the
FDA/US package insert guidelines.
4. Have a history of chronic disease(s) of the immune system, other than MS or a known
immunodeficiency syndrome.
5. Have comorbid conditions that preclude participation, including any condition that
might increase brain biomarkers such as traumatic brain injury (TBI), meningitis,
stroke, or drug abuse in the last 12 months or any other medical condition deemed
significant for increased biomarkers by the investigator.
6. Have an active/acute infection (bacterial, viral, fungal, etc.) at the time of screen
AND/OR baseline or within 4 weeks prior to or at the start of course 2 year 2 that
would interfere with the safety of the study.
7. Have a current or past significant history of poorly controlled diabetes mellitus,
obesity (BMI over 35) or anorexia (BMI under 18), hypertension or hyperlipidemia as
determined by the investigator.
8. Have a history or presence of malignancy other than basal cell epithelioma (BCE) or
cervical cancer in-situ following a complete excision. Cancer that has been absent for
more than 10 years and considered to be cured is allowed.
a. All standard cancer screening guidelines should be followed for subjects that are
treated with cladribine tablets during the course of the study.
9. Known liver conditions including the following:
1. History or current hepatic impairment considered moderate or severe. Subjects
with mild hepatic impairment can be considered at the investigator's discretion.
2. Current or known history of alcohol abuse. 3. Chronic liver or biliary diseases. 4. Total or conjugated bilirubin greater than the upper limit of normal range. 5. Alkaline phosphatase (AP) greater than 1.5 times the upper limit of the normal
range. 6. Aspartate transaminase (AST/ aka SGOT) and/or an alanine transaminase (ALT/aka
SGPT) greater than 2 times the upper limit of normal range.
7. Gamma-glutamyl-transferase (GGT) greater than 3 times the upper limit of normal.
10. History of or current renal Impairment that is considered moderate to severe.
(creatinine clearance below 50 mL per minute)
11. Any other significant medical condition that in the opinion of the investigator that
could potentially cause interference of complications of subject taking study
Investigational Product (IP).
12. Have a contraindication to a lumbar puncture. (i.e. abnormal coagulation panel, skin
infection at the location of Lumbar Puncture (LP), increased cranial pressure, etc.)
13. Any laboratory results at screen and/or prior to course 2 that are considered
significant, such as but not limited to, abnormal lymphocyte count, positive hepatitis
B and/or C screen, positive HIV test, etc. Any abnormal lab results must be approved
by the investigator prior to initiating the first AND second course of IP therapy.
14. Have a lymphocyte count that is not at least 800 cells per microliter before
initiating the second treatment course at week 48. If necessary, the second treatment
course can be delayed as per FDA/US package insert guidelines.
15. Unable to undergo the required MRI scans for any reason, including claustrophobia and
a history of hypersensitivity to Gd+.
16. Females who are pregnant, plan to become pregnant or who are breastfeeding during the
study or plan on becoming pregnant or breastfeeding within 6 months of the last dose
of cladribine tablets.
17. Males whose partner plans to become pregnant during the study or become pregnant
within 6 months of the last dose of cladribine tablets.
18. Screening labs may be repeated in 2-6 weeks if an abnormality is felt to be due to a
transient, reversible condition. 19. Subjects that have previously been treated with cladribine in any dosing form
(intravenous, subcutaneous, oral) are not allowed.
20. Subjects with a history of any of the following:
1. Prior alemtuzumab treatment. 2. Prior or current investigational or non-FDA approved DMT or procedure. 3. Prior or current stem cell transplant for any reason. 4. Treatment with ocrelizumab or rituximab within 12 months of last dose to baseline. 5. Treatment with natalizumab within 1 year of screen. If subject has a prior
history of treatment with natalizumab, the subject must also be JCV (John
Cunningham virus) negative or have JCV index of 0.5 or lower. A past JCV index
over 0.5 is exclusionary.
6. Treatment with fingolimod, teriflunomide or dimethyl fumarate (DMF) within 4
weeks prior to baseline. 7. Treatment with interferon(IFN) or glatiramer acetate(GA) within 4 weeks of
baseline. 8. Treatment with Intravenous immune globulin (IVIG) or plasmapheresis within 12
weeks prior to screening. 9. Treatment with an immunosuppressant such as cyclophosphamide, mitoxantrone,
azathioprine, mycophenolate within 3 years prior to screening.
10. Systemic corticosteroid within 2 weeks prior to screening. The screening period
may be extended up to 4 weeks for patients who have used systemic corticosteroids
but for a patient to be eligible for enrollment, no corticosteroids should be
administered between screening and baseline. 21. Treatment with concomitant drugs used for symptomatic treatment of spasticity or
neuropathic pain, (i.e. baclofen, lorazepam, or gabapentin) as long as they have been
stable dose for at least 30 days prior to screen. Medical Marijuana is allowed per
investigator discretion and where allowed by state law. Medical Marijuana must not
interfere with the subject's function.
