Trial Outcomes & Findings for Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis (NCT NCT04025554)

NCT ID: NCT04025554

Last Updated: 2024-12-27

Results Overview

Proportion of lesions in which the paramagnetic rim has been modulated at the end of the dosing period.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2024-12-27

Participant Flow

Participants were enrolled beginning on October 25, 2019 with the last participant enrolled on April 27, 2023. Candidates for participation were either 1) self referred, 2) referred by the Clinical Center Recruitment Office and NIH Clinical Research Volunteer Program or 3) identified during participation in an ongoing Neuroimmunology Clinic protocol.

Participant milestones

Measure	All Participants Participants with Multiple Sclerosis with at least one paramagnetic rim lesion noted on 7 Tesla MRI
Overall Study STARTED	8
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	All Participants Participants with Multiple Sclerosis with at least one paramagnetic rim lesion noted on 7 Tesla MRI
Overall Study Adverse Event	3

Baseline Characteristics

Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis

Baseline characteristics by cohort

Measure	All Participants n=8 Participants Participants with Multiple Sclerosis with at least one paramagnetic rim lesion on 7T MRI, treated with Anakinra
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	50.3 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Proportion of lesions in which the paramagnetic rim has been modulated at the end of the dosing period.

Outcome measures

Measure	Treatment Group n=25 Paramagnetic Rim Lesions Participants with Multiple Sclerosis with at least one paramagnetic rim lesion noted on 7 Tesla MRI, administered Anakinra starting at dose 100 mg/d up to a target dose of 300 mg/d	Weeks 12-24 Proportion of paramagnetic rim lesions diminished or disappeared during the 12-24 week time period	Weeks 0-24 Proportion of paramagnetic rim lesions diminished or disappeared at any time during the 0-24 week time period
Modulation of One or All Paramagnetic Rim Lesions	.04 proportion of rim lesions modulated	—	—

SECONDARY outcome

Timeframe: 24 weeks

The Nine-Hole Peg Test (9-HPT) is a standardized, quantitative assessment used to measure finger dexterity. The test is administered by asking the participant to take pegs from a container, one by one, and place them into holes on a board as quickly as possible. Participants must then remove the pegs from the holes, one by one, and replace them back into the container. The test is timed with a lower number suggesting faster finger dexterity and a higher number suggesting slower finger dexterity. The results represent the mean change from baseline to end of dosing.

Outcome measures

Measure	Treatment Group n=5 Participants Participants with Multiple Sclerosis with at least one paramagnetic rim lesion noted on 7 Tesla MRI, administered Anakinra starting at dose 100 mg/d up to a target dose of 300 mg/d	Weeks 12-24 Proportion of paramagnetic rim lesions diminished or disappeared during the 12-24 week time period	Weeks 0-24 Proportion of paramagnetic rim lesions diminished or disappeared at any time during the 0-24 week time period
Change in the 9-hole Peg Test (9HPT)	-0.42 seconds Standard Deviation 1.51	—	—

SECONDARY outcome

Timeframe: 24 weeks

The Symbol Digit Modalities Test (SDMT) is a neuropsychological test that assesses cognitive status, including processing speed, visual scanning, tracking, and motor speed. Participants are given a set of nine symbol-digit pairs and a sequence of symbols. They then have 90 seconds to match as many symbols in the sequence to their corresponding numbers as possible. The score is the number of correct substitutions within the 90 second interval, with a maximum of 110. The results represent a change from baseline to the end of dosing.

Outcome measures

Measure	Treatment Group n=5 Participants Participants with Multiple Sclerosis with at least one paramagnetic rim lesion noted on 7 Tesla MRI, administered Anakinra starting at dose 100 mg/d up to a target dose of 300 mg/d	Weeks 12-24 Proportion of paramagnetic rim lesions diminished or disappeared during the 12-24 week time period	Weeks 0-24 Proportion of paramagnetic rim lesions diminished or disappeared at any time during the 0-24 week time period
Change in the Symbol Digit Modalities Test (SDMT)	-3.6 number correct Standard Deviation 4.3	—	—

SECONDARY outcome

Timeframe: 24 weeks

The EDSS is a tool used to measure the severity of multiple sclerosis (MS). The EDSS is based on a combination of scores from eight functional systems (FS), i.e., Muscle weakness, Balance, Coordination and Tremor, Eye Movements, Speech/Swallowing, Unusual Sensations or Numbness, Bowel and Bladder, Eyesight, and Thinking and Memory, and the Disability Status Scale (DSS). The EDSS is a scale that ranges from 0 to 10, with higher scores indicating greater disability. Scores of 1.0 to 4.5 indicate a high degree of ambulatory ability, while scores of 5.0 to 9.5 indicate a loss of ambulatory ability. The results represent a change from baseline to the end of dosing.

Outcome measures

Measure	Treatment Group n=5 Participants Participants with Multiple Sclerosis with at least one paramagnetic rim lesion noted on 7 Tesla MRI, administered Anakinra starting at dose 100 mg/d up to a target dose of 300 mg/d	Weeks 12-24 Proportion of paramagnetic rim lesions diminished or disappeared during the 12-24 week time period	Weeks 0-24 Proportion of paramagnetic rim lesions diminished or disappeared at any time during the 0-24 week time period
Change in the Expanded Disability Status Scale (EDSS)	0 change in score on a scale Interval 0.0 to 0.0	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Participants underwent 7T MRI during the dosing period and the post-dosing period. The results presented describe the proportion of paramagnetic rim lesions in which the rim was diminished or disappeared during the dosing period (weeks 0-12), during the post-dosing period (weeks 12-24) and during the entire study (weeks 0-24).

Outcome measures

Measure	Treatment Group n=25 Paramagnetic Rim Lesions Participants with Multiple Sclerosis with at least one paramagnetic rim lesion noted on 7 Tesla MRI, administered Anakinra starting at dose 100 mg/d up to a target dose of 300 mg/d	Weeks 12-24 n=21 Paramagnetic Rim Lesions Proportion of paramagnetic rim lesions diminished or disappeared during the 12-24 week time period	Weeks 0-24 n=21 Paramagnetic Rim Lesions Proportion of paramagnetic rim lesions diminished or disappeared at any time during the 0-24 week time period
Change in Paramagnetic Rim Lesion at Any Time Point	0 Proportion of PRL changes Interval 0.0 to 0.14	0 Proportion of PRL changes Interval 0.0 to 0.0	0 Proportion of PRL changes Interval 0.0 to 0.14

SECONDARY outcome

Timeframe: Every 4 weeks for the duration of the study

Paramagnetic rim lesions are multiple sclerosis plaques showing signs of low-grade, ongoing inflammation on MRI. Participants underwent MRI every 4 weeks and we compared the change in size between the participant's paramagnetic rim lesions (PRL+) and non-paramagnetic rim lesions (PRL-). At each time point, the mean group volume of each PRL+ and PRL- was calculated. The results provided include the group means and confidence limits at each time point for PRL+ and PRL- lesion type.

Outcome measures

Measure	Treatment Group n=25 Lesions Participants with Multiple Sclerosis with at least one paramagnetic rim lesion noted on 7 Tesla MRI, administered Anakinra starting at dose 100 mg/d up to a target dose of 300 mg/d	Weeks 12-24 n=200 Lesions Proportion of paramagnetic rim lesions diminished or disappeared during the 12-24 week time period	Weeks 0-24 Proportion of paramagnetic rim lesions diminished or disappeared at any time during the 0-24 week time period
Change in Size of Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Baseline	168.9 mm^3 Interval 114.4 to 252.8	50.7 mm^3 Interval 44.8 to 57.7	—
Change in Size of Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 4	168.4 mm^3 Interval 113.6 to 253.0	50.3 mm^3 Interval 44.4 to 57.2	—
Change in Size of Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 8	167.2 mm^3 Interval 112.6 to 251.8	49.9 mm^3 Interval 44.1 to 56.7	—
Change in Size of Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 12	175.4 mm^3 Interval 117.9 to 264.5	50.7 mm^3 Interval 44.8 to 57.7	—
Change in Size of Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 16	171.3 mm^3 Interval 115.9 to 256.4	46.9 mm^3 Interval 41.6 to 53.2	—
Change in Size of Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 24	160.5 mm^3 Interval 108.9 to 239.9	47.8 mm^3 Interval 42.4 to 54.3	—

SECONDARY outcome

Timeframe: Every 4 weeks for the duration of the study

Paramagnetic rim lesions are multiple sclerosis plaques showing signs of low-grade, ongoing inflammation on MRI. T1 relaxation time is a measure of brain damage on MRI. Participants underwent MRI every 4 weeks and we compared the change in T1 relaxation time between the participant's paramagnetic rim lesions (PRL+) and non-paramagnetic rim lesions (PRL-) at each time point. The results provided include the group means and confidence limits at each time point for PRL+ and PRL- lesion type.

Outcome measures

Measure	Treatment Group n=25 Lesions Participants with Multiple Sclerosis with at least one paramagnetic rim lesion noted on 7 Tesla MRI, administered Anakinra starting at dose 100 mg/d up to a target dose of 300 mg/d	Weeks 12-24 n=200 Lesions Proportion of paramagnetic rim lesions diminished or disappeared during the 12-24 week time period	Weeks 0-24 Proportion of paramagnetic rim lesions diminished or disappeared at any time during the 0-24 week time period
Changes in T1 Relaxation Time Within Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Baseline	1723 ms Interval 1612.0 to 1858.0	1534 ms Interval 1416.0 to 1697.0	—
Changes in T1 Relaxation Time Within Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 4	1708 ms Interval 1599.0 to 1841.0	1522 ms Interval 1407.0 to 1680.0	—
Changes in T1 Relaxation Time Within Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 8	1713 ms Interval 1603.0 to 1848.0	1525 ms Interval 1409.0 to 1683.0	—
Changes in T1 Relaxation Time Within Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 12	1706 ms Interval 1597.0 to 1838.0	1522 ms Interval 1407.0 to 1679.0	—
Changes in T1 Relaxation Time Within Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 16	1709 ms Interval 1600.0 to 1841.0	1527 ms Interval 1410.0 to 1687.0	—
Changes in T1 Relaxation Time Within Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions Week 24	1728 ms Interval 1616.0 to 1865.0	1525 ms Interval 1409.0 to 1685.0	—

Adverse Events

All Participants

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	All Participants n=8 participants at risk Participants with Multiple Sclerosis with at least one paramagnetic rim lesion on 7T MRI, administered Anakinra starting at dose 100 mg/d.
Blood and lymphatic system disorders Lymphocyte count decreased	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Blood and lymphatic system disorders Anemia	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Gastrointestinal disorders Gastritis	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Injection site reaction (mild burning)	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Injection site reaction	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Injection site reaction (erythema)	62.5% 5/8 • Number of events 5 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Fatigue	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Injection site reaction (stinging)	12.5% 1/8 • Number of events 2 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Injection site reaction (pruritus)	37.5% 3/8 • Number of events 3 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Injection site reaction (edema)	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Injection site reaction (increased bleeding)	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Injection site reaction (pain)	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
General disorders Flu-like symptoms	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Infections and infestations Upper respiratory infection	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Infections and infestations Bronchial infection	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Injury, poisoning and procedural complications Fall	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Investigations Neutrophil count decreased	37.5% 3/8 • Number of events 3 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Investigations Platelet count decreased	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Metabolism and nutrition disorders Dehydration	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Musculoskeletal and connective tissue disorders Metabolism and nutrition disorders other specified; increased appetite	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - other; left achilles degenerative tendinosis	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Nervous system disorders Paresthesia	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Nervous system disorders Extrapyramidal disorder	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Nervous system disorders Paresthesia (worsening)	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Nervous system disorders Headache	25.0% 2/8 • Number of events 2 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Nervous system disorders Nervous system disorder - other; hypoesthesia (middle dorsal lateral part of the feet)	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Respiratory, thoracic and mediastinal disorders Postnasal drip	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Skin and subcutaneous tissue disorders Dry skin	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.
Skin and subcutaneous tissue disorders Alopecia	12.5% 1/8 • Number of events 1 • Adverse events were collected for the duration of study participation, i.e., 24 weeks +/- 7 days.

Additional Information

Dr. Daniel S. Reich

National Institutes of Health

Phone: 301-496-1801

Email: reichds@ninds.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place