A Multicenter Randomized Controlled Trial of Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Treatment-Resistant Relapsing Multiple Sclerosis (ITN077AI)
This is a multi-center prospective rater-masked (blinded) randomized controlled trial of 156 participants, comparing the treatment strategy of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) to the treatment strategy of Best Available Therapy (BAT) for treatment-resistant relapsing multiple sclerosis (MS). Participants will be randomized at a 1 to 1 (1:1) ratio. All participants will be followed for 72 months after randomization (Day 0, Visit 0).
⁃ 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) ≤ 6.0 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 disease activity in the 36 months prior to the screening visit (Visit -2). The two disease activity episodes will be a clinical MS relapse or MRI evidence of MS disease activity and must meet all the criteria as described below:
⁃ At least one episode of disease activity must occur following ≥ 1 month of treatment with an oral DMT approved by the FDA or MHRA for the treatment of relapsing MS, or a monoclonal antibody, specifically: dimethyl fumarate (Tecfidera®), diroximel fumarate, teriflunomide (Aubagio®), cladribine (Mavenclad®), daclizumab (Zinbryta®), siponimod (Mayzent®), ozanimod, fingolimod (Gilenya®), rituximab (Rituxan®), ocrelizumab (Ocrevus®), natalizumab (Tysabri®), alemtuzumab (Campath®, Lemtrada®), or ofatumumab (Arzerra®), and
⁃ At least one episode of disease activity must have occurred within the 12 months prior to the screening visit (Visit -2), and
⁃ At least one episode of disease activity must be a clinical MS relapse (see item c.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:
⁃ Cladribine, natalizumab, alemtuzumab, ocrelizumab, rituximab, and ofatumumab (after approval by the FDA for relapsing MS). Candidacy for treatment for each DMT is defined as meeting all of the following:
⁃ No prior disease activity 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.
⁃ Completion of SARS-CoV-2 vaccination series ≥ 14 days prior to randomization (Day 0).
⁃ Positive for VZV antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least 4 weeks prior to randomization (Day 0).
⁃ 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.