Best Available Therapy Versus Autologous Hematopoetic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS)

• Register: ClinicalTrials.gov
• Last refreshed on: 5 February 2024
• Main ID: NCT04047628
• Date of registration: 05/08/2019
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Best Available Therapy Versus Autologous Hematopoetic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) BEAT-MS
• Scientific title: A Multicenter Randomized Controlled Trial of Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Treatment-Resistant Relapsing Multiple Sclerosis (ITN077AI)
• Date of first enrolment: December 19, 2019
• Target sample size: 156
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04047628
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Paolo A. Muraro, MD, PhD
• Affiliation: Department of Medicine, Imperial College London

• Name: Jeffrey A. Cohen, MD
• Affiliation: Mellen Center for MS Treatment and Research, Cleveland Clinic

• Name: George E. Georges, MD
• Affiliation: Fred Hutchinson Cancer Center

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age 18 to 55 years, inclusive, at the time of the screening Visit -2.

2. Diagnosis of MS according to the 2017 McDonald Criteria139.

3. EDSS = 6.0 at the time of randomization (Day 0).

4. T2 abnormalities on brain MRI that fulfill the 2017 McDonald MRI criteria for
dissemination in space139. A detailed MRI report or MRI images must be available for
review by the site neurology investigator.

5. 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 described below:

1. At least one episode of disease activity must occur following = 1 month of
treatment with one of the following: (i) an oral DMT approved by the FDA for the
treatment of relapsing MS, or (ii) a monoclonal antibody approved by the FDA for
the treatment of relapsing MS, or (iii) rituximab. Qualifying DMTs include:
dimethyl fumarate, diroximel fumarate, monomethyl fumarate, teriflunomide,
cladribine, daclizumab, ponesimod, siponimod, ozanimod, fingolimod, rituximab,
ocrelizumab, natalizumab, alemtuzumab, ublituximab, and ofatumumab, and

2. At least one episode of disease activity must have occurred within the 12 months
prior to the screening visit (Visit -2), and

3. 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 c.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 (see
Section 3.5), and ii. MRI evidence of disease activity must include = 1 unique active
lesion on one or more brain or spinal cord MRIs. Detailed MRI reports or MRI images
must be available for review by the site neurology investigator. A unique active
lesion is defined as either of the following:

1. A gadolinium-enhancing lesion, or 2. A new non-enhancing T2 lesion compared to a
reference scan obtained not more than 36 months prior to the screening visit (Visit -2).

6. Candidacy for treatment with at least one of the following high efficacy BAT DMTs:
cladribine, natalizumab, alemtuzumab, ocrelizumab, ofatumumab, ublituximab and rituximab.
Candidacy for treatment for each BAT DMT is defined as meeting all of the following:

1. No prior disease activity episode, as defined in Inclusion Criterion #5, with the
candidate BAT DMT, and

2. No contraindication to the candidate BAT DMT, and

3. No treatment with the candidate BAT DMT in the 12 months prior to screening.

7. Completion of COVID-19 vaccination series, according to the current Centers for
Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices
(ACIP) recommendations, = 14 days prior to randomization (Day 0).

8. 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).

9. Insurance approval for MS treatment with at least one candidate BAT DMT (see
Inclusion Criterion #6).

10. Ability to comply with study procedures and provide informed consent, in the
opinion of the investigator.

11. Females of childbearing potential (defined in Section 5.4.3.1) and males with
female partners of childbearing potential are required to adhere to the contraception
provisions of Section 5.4.3.1.

12. For participants who use medicinal or recreational marijuana, willingness to
substitute MARINOL® if randomized to AHSCT (Section 5.4.2.6).

Exclusion Criteria:

1. Diagnosis of primary progressive MS according to the 2017 McDonald criteria.

2. History of neuromyelitis optica spectrum disorder or MOG antibody disease.

3. Prior treatment with an investigational agent within 3 months or 5 half-lives,
whichever is longer. Agents authorized by the FDA for prevention or treatment of
COVID-19 are not considered investigational.

4. Either of the following within one month prior to randomization (Day 0):

1. Onset of acute MS relapse, or

2. Treatment with intravenous methylprednisolone 1000 mg/day for 3 days or
equivalent.

5. Initiation of any BAT DMT (see Section 5.2.1) between Visit -2 and randomization (Day
0).

6. Brain MRI or cerebrospinal fluid (CSF) examination indicating a diagnosis of
progressive multifocal leukoencephalopathy (PML).

7. History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).

8. Presence of unexplained cytopenia, polycythemia, thrombocythemia or leukocytosis.

9. History of sickle cell anemia or other hemoglobinopathy.

10. Evidence of past or current hepatitis B or hepatitis C infection, including treated
hepatitis B or hepatitis C. Hepatitis B surface antibody following hepatitis B
immunization is not considered to be evidence of past infection.

11. Presence or history of mild to severe cirrhosis.

12. Hepatic disease with the presence of either of the following:

1. 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

2. Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) = 2.0 times
the ULN.

13. Positive COVID-19 PCR test, or alternative nucleic acid amplification test (NAAT) per
institutional standards, within 14 days prior to randomization (Day 0).

14. Evidence of HIV infection.

15. Positive QuantiFERON - TB Gold,TB Gold Plus, or T-SPOT®.TB test results. PPD
tuberculin test may be substituted for QuantiFERON - TB Gold, TB Gold Plus, or
T-SPOT®.TB test.

16. Active viral, bacterial, endoparasitic, or opportunistic infections.

17. Active invasive fungal infection.

18. 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
sp


Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Secondary Progressive Multiple Sclerosis

Relapsing Remitting Multiple Sclerosis

Relapsing Multiple Sclerosis

Intervention(s)

Procedure: Autologous Hematopoietic Stem Cell Transplantation

Biological: Best Available Therapy (BAT)

Primary Outcome(s)

Multiple Sclerosis (MS) Relapse-Free Survival [Time Frame: From Day 0 (Randomization to Treatment) Up to 36 Months (3 Years)]

Secondary Outcome(s)

Proportion of Participants with a Grade 3 or Higher Infection [Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)]

The Occurrence of Any Evidence of Multiple Sclerosis (MS) Disease Activity or Death From Any Cause [Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)]

The Occurrence of Confirmed Disability Improvement by the Kurtz Expanded Disability Status Scale (EDSS) [Time Frame: Day 0 (Randomization to Treatment) Up to Month 72 (6 Years)]

Proportion of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Recipients Who Experience Primary or Secondary Graft Failure [Time Frame: From Day of Transplant (Receipt of Peripheral Blood Stem Cells-PBSC Infusion) Up to Day 28 Post Transplant]

Proportion of Participants who Experience a Serious Adverse Event (SAE) [Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)]

The Occurence of Confirmed Disability Worsening by the Kurtz Expanded Disability Status Scale (EDSS) [Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)]

Proportion of Participants with Progressive Multifocal Leukoencephalopathy (PML) [Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)]

The Occurrence of Death From Any Cause: All-Cause Mortality [Time Frame: Day 0 (Randomization to Treatment) Up to Month 72 (6 Years)]

Number of Multiple Sclerosis (MS) Relapses Per Year [Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)]

Time to Neutrophil Engraftment Among Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Recipients [Time Frame: From Day of Graft Infusion (Receipt of Peripheral Blood Stem Cells-PBSC Infusion) Up to 72 Months (6 Years)]

Change in Serum Neurofilament Light Chain (NfL) Concentration [Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)]

Whole Brain Volume Change from Pre-Randomization Visit to the follow-up evaluations [Time Frame: From Visit Pre-R Up to 72 Months (6 Years)]

Secondary ID(s)

BMT CTN 1905

DAIT ITN077AI

UM1AI109565

NIAID CRMS ID#: 38573

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Immune Tolerance Network (ITN)

Rho Federal Systems Division, Inc.

PPD

Blood and Marrow Transplant Clinical Trials Network