Trial Outcomes & Findings for Tolebrutinib, a Brain-penetrant Bruton's Tyrosine Kinase Inhibitor, for the Modulation of Chronically Inflamed White Matter Lesions in Multiple Sclerosis (NCT NCT04742400)
NCT ID: NCT04742400
Last Updated: 2024-08-13
Results Overview
Paramagnetic rims indicate the presence of inflammation and ongoing demyelination and axonal transection at the lesion edge. The lesions under study were present for at least 6 months. The results represent the number of participants in whom at least the paramagnetic rim has disappeared in at least 1 lesion at the end of 48 weeks of tolebrutinib 60 mg.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
48 weeks
Results posted on
2024-08-13
Participant Flow
Participants with MS were recruited between April 1, 2021 and November 30, 2023. Participants were referred by both internal and external providers, and were self-referred.
Participant milestones
| Measure |
Tolebrutinib Cohort
Participants on Tolebrutinib 60 mg/day for 48 weeks.
|
Anti-CD20 Cohort
Participants on baseline Anti-CD20 continuing at least through week 48.
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
5
|
|
Overall Study
COMPLETED
|
7
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Tolebrutinib, a Brain-penetrant Bruton's Tyrosine Kinase Inhibitor, for the Modulation of Chronically Inflamed White Matter Lesions in Multiple Sclerosis
Baseline characteristics by cohort
| Measure |
Tolebrutinib Cohort
n=7 Participants
Participants on Tolebrutinib 60 mg/day for 48 weeks.
|
Anti-CD20 Cohort
n=5 Participants
Participants on baseline Anti-CD20 continuing at least through week 48.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
47.7 Years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
42 Years
STANDARD_DEVIATION 6.11 • n=7 Participants
|
45.1 Years
STANDARD_DEVIATION 7.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Paramagnetic Rim Lesions
|
9 Number of Paramagnetic Rim Lesions
n=5 Participants
|
4.5 Number of Paramagnetic Rim Lesions
n=7 Participants
|
8 Number of Paramagnetic Rim Lesions
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 weeksParamagnetic rims indicate the presence of inflammation and ongoing demyelination and axonal transection at the lesion edge. The lesions under study were present for at least 6 months. The results represent the number of participants in whom at least the paramagnetic rim has disappeared in at least 1 lesion at the end of 48 weeks of tolebrutinib 60 mg.
Outcome measures
| Measure |
Tolebrutinib Cohort
n=7 Participants
Participants on Tolebrutinib 60 mg/day for 48 weeks.
|
Anti-CD20 Cohort
n=5 Participants
Participants on baseline Anti-CD20 continuing at least through week 48.
|
|---|---|---|
|
Disappearance of Paramagnetic Rim Lesions at 48 Weeks of 60 mg of Tolebrutinib.
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: each patient visitTo assess safety and tolerability of 96 weeks of tolebrutinib 60 mg (initial cohort), or 48 weeks of treatment with tolebrutinib 60 mg and 96 weeks off treatment with tolebrutinib 120 mg (Cohort A), all following anti-CD20antibody.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline vs. 96 weeksTo assess the possible repair of chronically inflamed white matter lesions in which inflammation at the lesion edge has been modulated by tolebrutinib. A reduction of the T1 relaxation time would be compatible with lesion repair. A reduction in lesion size could indicate lesion repair.
Outcome measures
Outcome data not reported
Adverse Events
Tolebrutinib Cohort
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Anti-CD20 Cohort
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tolebrutinib Cohort
n=7 participants at risk
Participants on Tolebrutinib 60 mg/day for 48 weeks.
|
Anti-CD20 Cohort
n=5 participants at risk
Participants on baseline Anti-CD20 continuing at least through week 48.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
Other adverse events
| Measure |
Tolebrutinib Cohort
n=7 participants at risk
Participants on Tolebrutinib 60 mg/day for 48 weeks.
|
Anti-CD20 Cohort
n=5 participants at risk
Participants on baseline Anti-CD20 continuing at least through week 48.
|
|---|---|---|
|
Nervous system disorders
Weakness
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Psychiatric disorders
Insomnia
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Psychiatric disorders
Vivid dreams
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Renal and urinary disorders
Renal and urinary disorders other: hesitancy
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
Rash, maculopapular
|
28.6%
2/7 • Number of events 2 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
Skin lesion/insect bite
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Cardiac disorders
Asymptomatic conduction disorder
|
28.6%
2/7 • Number of events 2 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Cardiac disorders
Sinus bradycardia
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Ear and labyrinth disorders
Tinnitus
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Eye disorders
Presbyopia
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Eye disorders
Subconjunctival hemorrhage
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Gastrointestinal disorders
Nausea
|
28.6%
2/7 • Number of events 2 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Gastrointestinal disorders
Oral hemorrhage
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Gastrointestinal disorders
Stomach pain
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
General disorders
Bruising (worsening)
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
General disorders
Facial pain (left side)
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
General disorders
Fatigue
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
General disorders
Fever
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
General disorders
Peripheral edema
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Infections and infestations
Acute upper respiratory tract infection
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Infections and infestations
COVID-19
|
57.1%
4/7 • Number of events 4 • 48 weeks
|
40.0%
2/5 • Number of events 2 • 48 weeks
|
|
Injury, poisoning and procedural complications
Bruising and/or other injury
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
28.6%
2/7 • Number of events 2 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Injury, poisoning and procedural complications
Mechanical fall (skiing)
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Injury, poisoning and procedural complications
Right 2nd digit and right foot laceration
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Investigations
Elevated white blood cell count in cerebrospinal fluid
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Investigations
Hypokalemia, grade 1
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Investigations
Lipase increased
|
28.6%
2/7 • Number of events 2 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/7 • 48 weeks
|
40.0%
2/5 • Number of events 2 • 48 weeks
|
|
Investigations
Platelet count decreased
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
Meniscus tear
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Nervous system disorders
Bilateral lower extremity paresthesia
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Nervous system disorders
Cerebrospinal fluid leak
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Nervous system disorders
Extrapyramidal disorder
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Nervous system disorders
Headache
|
42.9%
3/7 • Number of events 3 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Nervous system disorders
Increased tingling in right upper extremity
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Nervous system disorders
Left leg heaviness
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Nervous system disorders
Leg weakness
|
14.3%
1/7 • Number of events 1 • 48 weeks
|
0.00%
0/5 • 48 weeks
|
|
Nervous system disorders
New lesion
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Nervous system disorders
Nystagmus
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
|
Nervous system disorders
Pyramidal tract syndrome
|
0.00%
0/7 • 48 weeks
|
20.0%
1/5 • Number of events 1 • 48 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place