Sequential Natalizumab - Alemtuzumab Therapy in Patients With Relapsing Forms of Multiple Sclerosis

Multiple Sclerosis (MS) Clinical Trial

— SUPPRESS  

Official title:

Sequential Natalizumab - Alemtuzumab Therapy in Patients With Relapsing Forms of Multiple Sclerosis (SUPPRESS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03135249
• Other study ID #: STU 112016-060
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2018
• Est. completion date: November 4, 2020

Study information

• Verified date: January 2022
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if a sequential combination therapy of natalizumab and alemtuzumab induces peripheral tolerance and reduces the annualized relapse rate (ARR) in patients with relapsing-remitting multiple sclerosis (RRMS).

Description:

To determine if treatment with alemtuzumab after natalizumab reduces the ARR in patients with RRMS. The goal of this trial is to establish a disease-free state over a 24 months period in patients who received the natalizumab-alemtuzumab sequential therapy. The target population for this study are RRMS patients nearing the end of their natalizumab treatment regimen.Participants will be recruited from four different sites. Patients who meet all inclusion/exclusion criteria will be eligible for enrollment in the study. Alemtuzumab (Lemtrada®) will be administered at a dose of 12 mg/d by intravenous (i.v.) infusion every day for five consecutive days within 14 days of the last dose of natalizumab. After 12 months, patients will be treated with a second course of alemtuzumab 12 mg/d by intravenous (i.v.) infusion every day for three consecutive days, and participants will be followed open-label for another 12 months per standard of care. Outside the scope of this study, the intention is to follow all study participants in participating centers long-term, and to record disease activity and treatment response. Natalizumab treatment sequesters leukocytes out of the central nervous system (CNS) into the peripheral blood. Immediate sequential alemtuzumab therapy will deplete these cells more completely than alemtuzumab monotherapy, and prevent reactivation of disease activity previously treated with natalizumab. Thus, investigators hypothesize that sequential natalizumab - alemtuzumab therapy will prevent disease activation after cessation of natalizumab, and will provide sustained disease remission in many patients. Clinical follow up by the treating physician will occur at months 0, 3, 6, 9, 12, 18 and 24 or immediately following clinical exacerbations months. During clinical visits, comprehensive medical history data will be obtained by the treating physician. Clinical visits due to suspected exacerbations associated with CNS (central nervous system) demyelination, and associated diagnostic studies and treatments, will be covered under the medical standard of care by third party payers. A recommendation to reevaluate the patient within 3 months following the clinical event to assess for extent of recovery will be made. Standardized MRI studies of the brain will be performed at 0, 6, 12 and 24 months. Clinical imaging studies of the brain will be performed during or immediately following the onset of a clinical exacerbation will be performed at the discretion of the site PI with scan costs covered under the medical standard of care. An end of study clinical MRI of the brain with and without contrast will be recommended to study participants at week 96 as medical standard of care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: November 4, 2020
• Est. primary completion date: November 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Age between 18 and 60 years, inclusive.

2. Diagnosis of relapsing forms of MS using revised McDonald Criteria1.

3. Expanded Disability Status Scale (EDSS) 0 - 5.5 (note: functional system changes in cerebral (or mental) functions and in bowel and bladder functions not used in determining EDSS for protocol eligibility).

4. Has had a minimum of 12 monthly doses of continuous natalizumab therapy (300 mg/d).

5. Understands English, and gives informed consent.

Exclusion Criteria:

1. Natalizumab failure based on clinician's discretion.

2. Any prior exposure to alemtuzumab.

3. Progressive MS.

4. A diagnosis of Progressive multifocal leukoencephalopathy (PML).

5. Known hypersensitivity to alemtuzumab.

6. Initiation of new immunosuppressant treatment after the subject becomes protocol-eligible (except for corticosteroids) or enrollment in a concurrent trial with immuno-active pharmacotherapies.

7. Uncontrolled diabetes mellitus defined as HbA1c > 8% and/or requiring intensive management.

8. History of cytopenia consistent with the diagnosis of myelodysplastic syndrome.

9. Clinically significant autoimmune disease other than MS that may affect the CNS, including neuromyelitis optica (NMO), systemic lupus erythematosus (SLE), or Behcet disease.

10. Active hepatitis B or C infection or evidence of cirrhosis.

11. HIV positivity.

12. Uncontrolled viral, fungal, or bacterial infection.

13. Positive pregnancy test or inability or unwillingness to use effective means of birth

control. Effective birth control is defined as:

1. Refraining from all acts of vaginal intercourse (abstinence),

2. Consistent use of birth control pills,

3. Tubal sterilization or male partner who has undergone vasectomy

4. Placement of intrauterine device

5. Use, with every act of intercourse, of a diaphragm with contraceptive jelly and/or condoms with contraceptive foam.

14. Presence of metallic objects implanted in the body that would preclude the ability of the subject to safely have MRI exams.

15. Psychiatric illness, mental deficiency, or cognitive dysfunction making compliance with treatment or informed consent impossible.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis (MS)
• Sclerosis

Intervention

Drug:
• Alemtuzumab
Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.

Locations

Country	Name	City	State
United States	UT Southwestern Medical center	Dallas	Texas
United States	VA North Texas Health Care System	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

References & Publications (27)

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Stüve O, Marra CM, Bar-Or A, Niino M, Cravens PD, Cepok S, Frohman EM, Phillips JT, Arendt G, Jerome KR, Cook L, Grand'Maison F, Hemmer B, Monson NL, Racke MK. Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. Arch Neurol. 2006 Oct;63(10):1383-7. — View Citation

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Neurological Disability Outcome	Neurological disability The Expanded Disability Status Scale (EDSS) will be utilized to measure the accumulation of neurological disability.; The EDSS is a scale providing a disability score (0 to 10) based on neurological examination and information about how the patient is able to perform tasks such as long walking. Higher the score, worse the outcomes.	12 months
Other	Quality of Life Outcome	Quality of life (QoL) will be measured by a pre-defined, self-administered testing battery. It measures the pleasure one derives from being able to do their work well, feelings of hopelessness and difficulties in dealing with work or in doing their job effectively, and work-related, secondary exposure to extremely stressful events. Possible scores range from 0-100, with higher scores indicating a better quality of life.	12 months
Primary	Annualized Relapse Rate (ARR) From the Time of Cessation of Natalizumab Treatment.	The goal of this trial is to establish a disease-free state over a 24 months period in patients who received the natalizumab-alemtuzumab sequential therapy.; ARR was the number of confirmed relapses in a year, calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of time in study.	12 months
Primary	Relapse-free Period	Relapse free period, number of months until relapse, was measured only among participants who may relapse.	Baseline until progression up to 12 months
Secondary	Number of New T2 Lesions	Number of new T2 lesions as measured by MRI.	12 months
Secondary	Number of Enlarging T2 Lesions	Number of enlarging T2 lesions as measured by MRI.	12 months
Secondary	Number of Gadolinium (Gd)-Enhancing Lesions	Number of gadolinium (Gd)-enhancing lesions as measured by MRI.	12 months