Multiple SclerosisPhase 4NCT02683863
Pharmacokinetics of DMF and the Effects of DMF on Exploratory Biomarkers
A Phase 4 study testing BG00012 (DMF) (Tecfidera®.) in people with Multiple Sclerosis, run by Multiple Sclerosis Center of Northeastern New York at 1 site in United States.
Trial summary
The purpose of this study is to explore whether DMF (Dimethyl Fumarate) or MMF (monomethyl fumarate) its main bioactive metabolite, is capable of entering the central nervous system in SPMS patients that are being treated with Tecfidera®. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- BG00012 (DMF) (Tecfidera®.)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2015to 31 Jan 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- To be eligible to participate in this study, candidates must meet the following eligibility criteria at screening, or at the timepoint specified in the individual eligibility criterion listed:
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local patient privacy regulations. Subjects must provide separate informed consent to participate in this CSF study.
- Aged 25 to 65 years-old, inclusive, at the time of informed consent.
- Male of female subject with a confirmed diagnosis of SPMS.
- EDSS score between 3 and 7, inclusive, at screening.
- Weight should be between 130 and 200 lb.
Who cannot join
- Candidates will be excluded from study entry if any of the following exclusion criteria exist at screening, or at the timepoint specified in the individual criterion listed:
- Unable or unwilling to provide informed consent. (Subjects must provide separate informed consent for this study.)
- A MS relapse, as determined by the Investigator, which occurred within 90 days prior to screening, or the subject has not stabilized from a previous relapse prior to screening.
- Any contraindication to having a brain magnetic resonance imaging (MRI) (e.g., pacemaker, MRI-incompatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed) or contraindication for administration of gadolinium-contrast agent.
- Clinically significant brain MRI finding other than those related to MS, as judged by the Investigator, at screening.
- Any contraindications to having a LP (e.g., aspirin greater than 325 mg/day, warfarin, clopidrogel, decreased platelet count, prolonged PT or PTT more than 1 ½ over normal) as determined by history and Investigator decision.
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- Evidence of history of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, diabetes mellitus) with the exception of MS.
- Any sign of chronic active infection, requiring antibiotic treatment (refer to Exclusion 23) (e.g., urinary tract infection, bronchitis, hepatitis, and tuberculosis) except for those requiring topical medication for treatment (e.g., athletes foot), or screening laboratory evidence consistent with a significant chronic active acute infection requiring systemic treatment.
- Pregnant; or breastfeeding females; or males of fathering potential or females of childbearing potential who are unwilling or unable to use an effective method of contraception as outlined in this protocol (Section 12.5) for the duration of the study and for at least 28 days after the last dose of DMF use in this protocol. For females of childbearing potential, a positive pregnancy test at any time within the protocol.
- Known positive human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody tests indicative of present or prior infection.
- Any abnormal hematology values or clinical chemistry values judged by the Investigator or Sponsor as clinically significant, including white blood cell count (WBC) 3500/mm3, or absolute lymphocyte count lower limit of normal.
- Positive Quantiferon-Tuberculosis Gold In-Tube test (QFT-GIT) at screening or known history of active tuberculosis not adequately treated.
- Any malignancy within 5 years, except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis.
- Any clinical, CSF, or MRI evidence for progressive multifocal leukoencephalopathy, from historical MRI.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
- Subjects participating in or expecting to participate in other interventional clinical trials, except those participating in Study US-BGT-US-10766 at the same site.
- History of drug or alcohol abuse (as defined by the Investigator) within 2 years prior to screening.
- Previous exposure to DMF for disease management at any time in the past.
- History of severe allergic or anaphylactic reactions or known drug hypersensitivity to fumaric acid or fumaric acid esters.
- Treatment with methylprednisolone or other systemic corticosteroid for MS relapse or otherwise within 30 days prior to Day 1 of study treatment.
- Treatment with MS disease modifying therapies as follows:
- Beta interferons (interferon beta-1a [Avonex® or Rebif®] or interferon beta-1b [Betaseron®], or glatiramer acetate [Copaxone®] within 6 weeks prior to Baseline.
- Fingolimod (Gilenya®), teriflunomide (Aubagio®) within 6 months prior to Baseline, except teriflunomide washout with accelerated elimination and verification of zero serum levels of teriflunomide prior Baseline.
- Natalizumab (Tysabri®) within 6 months prior to Screening OR 1 month prior to screening if subject has a positive Nabs (neutralizing antibodies) to Tysabri® Treatment within the past 5 years or current treatment with any of the following agents: cyclosporine, cladribine, agents that are immunosuppressive (e.g., entanercept), murine protein, T-cell vaccination), or stem cell transplantation prior to Screening.
- Treatment within the past 2 years with rituximab, IVIG, or mycophenolate
- Receipt of any non-live vaccine within the previous 14 days or live vaccine within 30 days prior to first dose of study treatment.
- Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study treatment, whichever is longer.
- Use of antibiotics for any reason within 3 months of Screening. Inclusion Criteria (for Normal Control Volunteers Only)
- To be eligible to participate in this study, normal control candidates must meet the following eligibility criteria at screening:
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local patient privacy regulations. Subjects must provide separate informed consent to participate in this CSF study.
- Male or female, aged 25 to 65 years-old, inclusive, at the time of informed consent.
- Weight should be between 130 and 200 lb. Exclusion Criteria (for Normal Control Volunteers Only)
- Normal control candidates will be excluded from study entry if any of the following exclusion criteria exist at screening, or at the timepoint specified in the individual criterion listed:
- Unable or unwilling to provide informed consent. (Subjects must provide separate informed consent for this study.)
- Any contraindications to having a LP (e.g., aspirin greater than 325 mg/day, warfarin, clopidrogel, decreased platelet count, prolonged PT or PTT more than 1 ½ over normal) as determined by history and Investigator decision.
- Evidence of history of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, diabetes mellitus) with the exception of MS.
- Any sign of chronic active infection, requiring antibiotic treatment (refer to Exclusion 23) (e.g., urinary tract infection, bronchitis, hepatitis, and tuberculosis) except for those requiring topical medication for treatment (e.g., athletes foot), or screening laboratory evidence consistent with a significant chronic active acute infection requiring systemic treatment.
- Pregnant; or breastfeeding females; or males of fathering potential or females of childbearing potential who are unwilling or unable to use an effective method of contraception as outlined in this protocol (Section 12.5) for the duration of the study and for at least 28 days after the last dose of DMF use in this protocol. For females of childbearing potential, a positive pregnancy test at any time within the protocol.
- Known positive human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody tests indicative of present or prior infection.
- Any abnormal hematology values or clinical chemistry values judged by the Investigator or Sponsor as clinically significant, including white blood cell count (WBC) 3500/mm3, or absolute lymphocyte count lower limit of normal.
- Positive Quantiferon-Tuberculosis Gold In-Tube test (QFT-GIT) at screening or known history of active tuberculosis not adequately treated.
- Any malignancy within 5 years, except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis.
- Any clinical, CSF, or MRI evidence for progressive multifocal leukoencephalopathy, from historical MRI.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
- Subjects participating in or expecting to participate in other interventional clinical trials, except those participating in Study US-BGT-US-10766 at the same site.
- History of drug or alcohol abuse (as defined by the Investigator) within 2 years prior to screening.
Trial locations and contacts
1 site in 1 country.
United States1 site
Multiple Sclerosis Center of Northeastern New York
Latham, New York, 12110
About this study
Official title: An Open Label Study of the Pharmacokinetics of DMF and the Effects of DMF on Exploratory Biomarkers in Subjects With Secondary Progressive Multiple Sclerosis
The purpose of this study is to explore whether DMF (Dimethyl Fumarate) or MMF (monomethyl fumarate) its main bioactive metabolite, is capable of entering the central nervous system in SPMS patients that are being treated with Tecfidera®. PK samples (pharmacokinetics - or the amount of study drug in blood) will be tested to compare with PK samples, the amount of study drug, in spinal fluid (CSF).
- Conditions
- Multiple Sclerosis
- Being tested
- BG00012 (DMF) (Tecfidera®.)
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BG00012 (DMF) (Tecfidera®.)Drug
Subjects will take DMF 120 mg BID for the first 4 weeks of treatment followed by DMF 240 mg BID for 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Other | There will be 4 CSF sampling groups at the Week 6 visit for PK assessment:
1. Four subject for CSF samples 3 hours after dosing Receives: Drug: BG00012 (DMF) (Tecfidera®.) |
| Group 2 | Other | 2. Four subjects for CSF samples 5 hours after dosing Receives: Drug: BG00012 (DMF) (Tecfidera®.) |
| Group 3 | Other | 3. Four subjects for CSF samples 7 hours after dosing Receives: Drug: BG00012 (DMF) (Tecfidera®.) |
| Group 4 | Other | 4. Four subjects for predose CSF samples Receives: Drug: BG00012 (DMF) (Tecfidera®.) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in CSF with SPMS.
Concentration of DMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
Measured: post-DMF treatment in Week 6
The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in plasma in subjects with SPMS.
Concentration of DMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
Measured: treatment in week 6
The primary objective of the study is to investigate the PK (drug level) of MMF(the primary metabolite of study drug) in CSF with SPMS.
Concentration of MMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
Measured: treatment in week 6
The primary objective of the study is to investigate the PK (drug level) of MMF( the primary metabolite of study drug) in plasma in subjects with SPMS.
Concentration of MMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
Measured: treatment in week 6
The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in CSF with SPMS.
Concentration of DMF conjugate in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
Measured: treatment in week 6
The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in plasma in subjects with SPMS.
Concentration of DMF conjugate in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
Measured: treatment in week 6
The primary objective of the study is to investigate the PK (drug level) of MMF (the primary metabolite of study drug) conjugate in CSF with SPMS.
Concentration of MMF conjugate in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
Measured: treatment in week 6
The primary objective of the study is to investigate the PK (drug level) of MMF( the primary metabolite of study drug) conjugate in plasma in subjects with SPMS.
Concentration of MMF conjugate in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
Measured: treatment in week 6
Secondary outcomes (7)
A secondary objective is to assess the effects of DMF on PD biomarkers downstream of Nrf2 in the CSF of subjects with SPMS.
PD biomarkers downstream of Nrf2, such as NAD(P)H hydrogenase [quinone 1], heme oxygenase-1, and aldo-keto reductase family 1 member B8 that have not been evaluated in CNS.
Measured: at 28 weeks
A secondary objective is to assess the effects of DMF on biomarkers of inflammation in the CSF of subjects with SPMS.
Biomarkers of inflammation (e.g., osteopontin, B cell activating factor, chemokines, and matrix metalloproteinase 9), which may reflect pathogenesis in SPMS.
Measured: at 28 weeks
A secondary objective is to assess the effects of DMF on biomarkers of neuroaxonal damage in the CSF of subjects with SPMS.
Biomarkers of neuroaxonal damage (e.g., neurofilament, myelin basic protein, glial fibrillary acidic protein, and neural cell adhesion molecule), which may reflect pathogenesis in SPMS.
Measured: at 28 weeks
A secondary objective is to assess the effects of DMF on biomarkers of oxidative stress in the CSF of subjects with SPMS.
Biomarkers of oxidative stress (e.g., myeloperoxidase, 8-Oxo-2'-deoxyguanosine and RNA biomarkers), which may reflect pathogenesis in SPMS
Measured: at 28 weeks
A secondary objective is to assess the effects of DMF on myelin lipid biomarkers in the CSF of subjects with SPMS.
Myelin lipid biomarkers (e.g., cholesterol, galactoceramide, sulfatides, and sphingomyelin), which may correlate with disability progression in MS patients.
Measured: at 28 weeks
A secondary objective is to assess the effects of DMF on pharmacogenomic biomarkers in the CSF of subjects with SPMS.
Pharmacogenomic biomarkers: DNA analysis from blood samples.
Measured: at 28 weeks
A secondary objective is to assess the effects of DMF on RNA samples from CSF cellular pellet for transcriptionomics in the CSF of subjects with SPMS.
RNA samples from CSF cellular pellet for transcriptionomics.
Measured: at 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2016 (estimated)
- Study startAug 2015
- Primary completion31 Jan 2017
- Study completion31 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Multiple Sclerosis Center of Northeastern New York
- Sponsor type
- University, hospital or other
- Collaborators
- Biogen
- Responsible party
- Sponsor
- Investigators
- Keith Edwards, M.D, Principal investigator, MS Center of Northeastern NY
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02683863
- Sponsor's protocol ID
- BG12-001
- Status last verified
- Mar 2017
- First submitted
- 14 Jan 2016
- Last updated
- 22 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol. 2012 Nov 5;8(11):647-56. doi: 10.1038/nrneurol.2012.168. Epub 2012 Sep 25.
PubMed 23007702Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Lassmann H. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009 May;132(Pt 5):1175-89. doi: 10.1093/brain/awp070. Epub 2009 Mar 31.
PubMed 19339255Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain. 2005 Nov;128(Pt 11):2705-12. doi: 10.1093/brain/awh641. Epub 2005 Oct 17.
PubMed 16230320Lassmann H. New concepts on progressive multiple sclerosis. Curr Neurol Neurosci Rep. 2007 May;7(3):239-44. doi: 10.1007/s11910-007-0036-0.
PubMed 17488590Calkins MJ, Johnson DA, Townsend JA, Vargas MR, Dowell JA, Williamson TP, Kraft AD, Lee JM, Li J, Johnson JA. The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease. Antioxid Redox Signal. 2009 Mar;11(3):497-508. doi: 10.1089/ars.2008.2242.
PubMed 18717629Linker RA, Lee DH, Ryan S, van Dam AM, Conrad R, Bista P, Zeng W, Hronowsky X, Buko A, Chollate S, Ellrichmann G, Bruck W, Dawson K, Goelz S, Wiese S, Scannevin RH, Lukashev M, Gold R. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011 Mar;134(Pt 3):678-92. doi: 10.1093/brain/awq386.
PubMed 21354971Scannevin RH, Chollate S, Jung MY, Shackett M, Patel H, Bista P, Zeng W, Ryan S, Yamamoto M, Lukashev M, Rhodes KJ. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. J Pharmacol Exp Ther. 2012 Apr;341(1):274-84. doi: 10.1124/jpet.111.190132. Epub 2012 Jan 20.
PubMed 22267202Ellrichmann G, Petrasch-Parwez E, Lee DH, Reick C, Arning L, Saft C, Gold R, Linker RA. Efficacy of fumaric acid esters in the R6/2 and YAC128 models of Huntington's disease. PLoS One. 2011 Jan 31;6(1):e16172. doi: 10.1371/journal.pone.0016172.
PubMed 21297955Ghoreschi K, Bruck J, Kellerer C, Deng C, Peng H, Rothfuss O, Hussain RZ, Gocke AR, Respa A, Glocova I, Valtcheva N, Alexander E, Feil S, Feil R, Schulze-Osthoff K, Rupec RA, Lovett-Racke AE, Dringen R, Racke MK, Rocken M. Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells. J Exp Med. 2011 Oct 24;208(11):2291-303. doi: 10.1084/jem.20100977. Epub 2011 Oct 10.
PubMed 21987655Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT; DEFINE Study Investigators. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012 Sep 20;367(12):1098-107. doi: 10.1056/NEJMoa1114287.
PubMed 22992073Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT; CONFIRM Study Investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012 Sep 20;367(12):1087-97. doi: 10.1056/NEJMoa1206328.
PubMed 22992072Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996 Apr;46(4):907-11. doi: 10.1212/wnl.46.4.907.
PubMed 8780061Comi G. Disease-modifying treatments for progressive multiple sclerosis. Mult Scler. 2013 Oct;19(11):1428-36. doi: 10.1177/1352458513502572.
PubMed 24062415
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Study of the Pharmacokinetics of DMF and the Effects of DMF on Exploratory Biomarkers in Subjects With Secondary Progressive Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT02683863
- Acronym / sponsor ID
- BG12-001
- Conditions
- Multiple Sclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Multiple Sclerosis Center of Northeastern New YorkUniversity, hospital or other
- Collaborators
- Biogen
- Study start
- Aug 2015
- Primary completion
- 31 Jan 2017 (actual)
- Study completion
- 31 Jan 2017 (actual)
- First posted
- 17 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to explore whether DMF (Dimethyl Fumarate) or MMF (monomethyl fumarate) its main bioactive metabolite, is capable of entering the central nervous system in SPMS patients that are being treated with Tecfidera®. PK samples (pharmacokinetics - or the amount of study drug in blood) will be tested to compare with PK samples, the amount of study drug, in spinal fluid (CSF).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Other | Drug: BG00012 (DMF) (Tecfidera®.)There will be 4 CSF sampling groups at the Week 6 visit for PK assessment: 1. Four subject for CSF samples 3 hours after dosing |
| Group 2 | Other | Drug: BG00012 (DMF) (Tecfidera®.)2. Four subjects for CSF samples 5 hours after dosing |
| Group 3 | Other | Drug: BG00012 (DMF) (Tecfidera®.)3. Four subjects for CSF samples 7 hours after dosing |
| Group 4 | Other | Drug: BG00012 (DMF) (Tecfidera®.)4. Four subjects for predose CSF samples |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- To be eligible to participate in this study, candidates must meet the following eligibility criteria at screening, or at the timepoint specified in the individual eligibility criterion listed:
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local patient privacy regulations. Subjects must provide separate informed consent to participate in this CSF study.
- Aged 25 to 65 years-old, inclusive, at the time of informed consent.
- Male of female subject with a confirmed diagnosis of SPMS.
- EDSS score between 3 and 7, inclusive, at screening.
Key exclusion criteria (46 listed)
- Candidates will be excluded from study entry if any of the following exclusion criteria exist at screening, or at the timepoint specified in the individual criterion listed:
- Beta interferons (interferon beta-1a [Avonex® or Rebif®] or interferon beta-1b [Betaseron®], or glatiramer acetate [Copaxone®] within 6 weeks prior to Baseline.
- Fingolimod (Gilenya®), teriflunomide (Aubagio®) within 6 months prior to Baseline, except teriflunomide washout with accelerated elimination and verification of zero serum levels of teriflunomide prior Baseline.
- Natalizumab (Tysabri®) within 6 months prior to Screening OR 1 month prior to screening if subject has a positive Nabs (neutralizing antibodies) to Tysabri® Treatment within the past 5 years or current treatment with any of the following agents: cyclosporine, cladribine, agents that are immunosuppressive (e.g., entanercept), murine protein, T-cell vaccination), or stem cell transplantation prior to Screening.
- Treatment within the past 2 years with rituximab, IVIG, or mycophenolate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BG00012 (DMF) (Tecfidera®.)Subjects will take DMF 120 mg BID for the first 4 weeks of treatment followed by DMF 240 mg BID for 24 weeks. | Drug | Group 1, Group 2, Group 3, Group 4 |
Primary outcome
The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in CSF with SPMS.
Time frame: post-DMF treatment in Week 6
Concentration of DMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in plasma in subjects with SPMS.
Time frame: treatment in week 6
Concentration of DMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
The primary objective of the study is to investigate the PK (drug level) of MMF(the primary metabolite of study drug) in CSF with SPMS.
Time frame: treatment in week 6
Concentration of MMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
The primary objective of the study is to investigate the PK (drug level) of MMF( the primary metabolite of study drug) in plasma in subjects with SPMS.
Time frame: treatment in week 6
Concentration of MMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in CSF with SPMS.
Time frame: treatment in week 6
Concentration of DMF conjugate in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in plasma in subjects with SPMS.
Time frame: treatment in week 6
Concentration of DMF conjugate in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
The primary objective of the study is to investigate the PK (drug level) of MMF (the primary metabolite of study drug) conjugate in CSF with SPMS.
Time frame: treatment in week 6
Concentration of MMF conjugate in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
The primary objective of the study is to investigate the PK (drug level) of MMF( the primary metabolite of study drug) conjugate in plasma in subjects with SPMS.
Time frame: treatment in week 6
Concentration of MMF conjugate in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
7 secondary outcomes
A secondary objective is to assess the effects of DMF on PD biomarkers downstream of Nrf2 in the CSF of subjects with SPMS.
Time frame: at 28 weeks
A secondary objective is to assess the effects of DMF on biomarkers of inflammation in the CSF of subjects with SPMS.
Time frame: at 28 weeks
A secondary objective is to assess the effects of DMF on biomarkers of neuroaxonal damage in the CSF of subjects with SPMS.
Time frame: at 28 weeks
A secondary objective is to assess the effects of DMF on biomarkers of oxidative stress in the CSF of subjects with SPMS.
Time frame: at 28 weeks
A secondary objective is to assess the effects of DMF on myelin lipid biomarkers in the CSF of subjects with SPMS.
Time frame: at 28 weeks
A secondary objective is to assess the effects of DMF on pharmacogenomic biomarkers in the CSF of subjects with SPMS.
Time frame: at 28 weeks
A secondary objective is to assess the effects of DMF on RNA samples from CSF cellular pellet for transcriptionomics in the CSF of subjects with SPMS.
Time frame: at 28 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2017.
- Background: PubMed 23007702Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol. 2012 Nov 5;8(11):647-56. doi: 10.1038/nrneurol.2012.168. Epub 2012 Sep 25.
- Background: PubMed 19339255Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Lassmann H. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009 May;132(Pt 5):1175-89. doi: 10.1093/brain/awp070. Epub 2009 Mar 31.
- Background: PubMed 16230320Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain. 2005 Nov;128(Pt 11):2705-12. doi: 10.1093/brain/awh641. Epub 2005 Oct 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith Edwards, M.D principal investigator
MS Center of Northeastern NY
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing BG00012 (DMF) (Tecfidera®.) in people with Multiple Sclerosis, run by Multiple Sclerosis Center of Northeastern New York at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in CSF with SPMS. (time frame: post-DMF treatment in Week 6). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02683863, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2017.