RECRUITING

A Prospective Biomarker Study in Active SPMS Subjects Treated With Cladribine Tablets

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to explore the concept that biomarker sensitivity will detect activity in Multiple Sclerosis (MS) subjects and allow appropriate change in treatment to prevent dysfunction.

Official Title

A Prospective Biomarker Study in Active Secondary Progressive Multiple Sclerosis (SPMS)Subjects Treated With Cladribine Tablets

Quick Facts

Study Start:2020-09-16

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04550455

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:21 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 13. If Male: must be willing to use contraception to avoid contributing to pregnancies 6 months following the last dose of study medication.	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. 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.

Inclusion Criteria

Exclusion 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
13. If Male: must be willing to use contraception to avoid contributing to pregnancies 6 months following the last dose of study medication.

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.
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.

Contacts and Locations

Study Contact

Judy Button

CONTACT

518-785-1000

jbutton@tristateneuro.com

Vineetha Kamath

CONTACT

518-785-1000

vkamath@tristateneuro.com

Principal Investigator

Keith R Edwards, M.D.

STUDY_DIRECTOR

MS Center of Northeastern New York, P.C.

Study Locations (Sites)

Multiple Sclerosis Center of Northeastern New York, P.C.

Latham, New York, 12110

United States

Collaborators and Investigators

Sponsor: Keith Edwards, M.D.

Keith R Edwards, M.D., STUDY_DIRECTOR, MS Center of Northeastern New York, P.C.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-09-16

Study Completion Date2025-12

Study Record Updates

Study Start Date2020-09-16

Study Completion Date2025-12

Terms related to this study

Additional Relevant MeSH Terms

Multiple Sclerosis