Trial Outcomes & Findings for Sequential Natalizumab - Alemtuzumab Therapy in Patients With Relapsing Forms of Multiple Sclerosis (NCT NCT03135249)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

9 participants

Primary outcome timeframe

12 months

Results posted on

2022-02-15

Participant Flow

Participant milestones

Participant milestones
Measure	Alemtuzumab Treatment. Patients with relapsing-remitting multiple sclerosis previously treated with natalizumab, the following treatment arms with alemtuzumab will be implemented: Year One: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for five days to be given within eight hours after dilution. Year Two: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for three days to be given within eight hours after dilution. Alemtuzumab: Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Overall Study STARTED	9
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alemtuzumab Treatment. n=9 Participants Patients with relapsing-remitting multiple sclerosis previously treated with natalizumab, the following treatment arms with alemtuzumab will be implemented: Year One: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for five days to be given within eight hours after dilution. Year Two: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for three days to be given within eight hours after dilution. Alemtuzumab: Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Sex: Female, Male Female	7 Participants n=93 Participants
Sex: Female, Male Male	2 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants
Race (NIH/OMB) White	7 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	9 Participants n=93 Participants

PRIMARY outcome

Timeframe: 12 months

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.

Outcome measures

Outcome measures
Measure	Alemtuzumab Treatment. n=9 Participants Patients with relapsing-remitting multiple sclerosis previously treated with natalizumab, the following treatment arms with alemtuzumab will be implemented: Year One: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for five days to be given within eight hours after dilution. Year Two: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for three days to be given within eight hours after dilution. Alemtuzumab: Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Annualized Relapse Rate (ARR) From the Time of Cessation of Natalizumab Treatment.	0 number of relapses in a year Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: Baseline until progression up to 12 months

Population: We are intending to report the number of months until relapse and no relapses occurred. This outcome was not measured because there was no relapse.

Relapse free period, number of months until relapse, was measured only among participants who may relapse.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Number of new T2 lesions as measured by MRI.

Outcome measures

Outcome measures
Measure	Alemtuzumab Treatment. n=9 Participants Patients with relapsing-remitting multiple sclerosis previously treated with natalizumab, the following treatment arms with alemtuzumab will be implemented: Year One: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for five days to be given within eight hours after dilution. Year Two: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for three days to be given within eight hours after dilution. Alemtuzumab: Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Number of New T2 Lesions	0 lesions Standard Deviation 0

SECONDARY outcome

Timeframe: 12 months

Number of enlarging T2 lesions as measured by MRI.

Outcome measures

Outcome measures
Measure	Alemtuzumab Treatment. n=9 Participants Patients with relapsing-remitting multiple sclerosis previously treated with natalizumab, the following treatment arms with alemtuzumab will be implemented: Year One: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for five days to be given within eight hours after dilution. Year Two: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for three days to be given within eight hours after dilution. Alemtuzumab: Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Number of Enlarging T2 Lesions	0 lesions Standard Deviation 0

SECONDARY outcome

Timeframe: 12 months

Number of gadolinium (Gd)-enhancing lesions as measured by MRI.

Outcome measures

Outcome measures
Measure	Alemtuzumab Treatment. n=9 Participants Patients with relapsing-remitting multiple sclerosis previously treated with natalizumab, the following treatment arms with alemtuzumab will be implemented: Year One: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for five days to be given within eight hours after dilution. Year Two: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for three days to be given within eight hours after dilution. Alemtuzumab: Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Number of Gadolinium (Gd)-Enhancing Lesions	0 lesions Standard Deviation 0

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: 2 patients did not complete a 12 month EDSS assessment.

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.

Outcome measures

Outcome measures
Measure	Alemtuzumab Treatment. n=7 Participants Patients with relapsing-remitting multiple sclerosis previously treated with natalizumab, the following treatment arms with alemtuzumab will be implemented: Year One: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for five days to be given within eight hours after dilution. Year Two: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for three days to be given within eight hours after dilution. Alemtuzumab: Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Neurological Disability Outcome	3.14 score on a scale Standard Deviation 1.49

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: We were not able to collect data for 2 out of 6 participants at UTSW and 3 participants at subsite were administered incorrect versions of the questionnaire which cannot be compared to the version they were supposed to and hence not analyzed for these participants.

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.

Outcome measures

Outcome measures
Measure	Alemtuzumab Treatment. n=4 Participants Patients with relapsing-remitting multiple sclerosis previously treated with natalizumab, the following treatment arms with alemtuzumab will be implemented: Year One: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for five days to be given within eight hours after dilution. Year Two: Alemtuzumab 12 mg (1.2 ml) IV Infusion via pump over a minimum of four hours daily for three days to be given within eight hours after dilution. Alemtuzumab: Alemtuzumab is a humanized monoclonal therapeutic antibody that rapidly depletes cluster of differentiation 52 (CD52)+ cells.
Quality of Life Outcome	71.38 score on a scale Standard Deviation 21.04

Adverse Events

Alemtuzumab Treatment.

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Olaf Stuve, Principal Investigator

UT Southwestern Medical Center

Phone: 12146484559

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place