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Also known as Diroximel
Diroximel fumarate · 3 trials · 2 indications
An adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether/not related to the medicinal (investigational) product. An AE was considered treatment-emergent if it starts or worsens on or after the date of the first dose of study drug in the study until 1 day after the last dose of treatment, or completion of the safety follow-up visit, if applicable.(i.e. for participants who prematurely discontinued study treatment or withdrew from the study) . An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event. TEAEs included both serious and non-serious TEAEs.
Laboratory assessments included hematology, blood chemistry, and urinalysis parameters. Hematology parameters:basophils, hematocrit, red blood cell, total and differential leukocytes, platelets, lymphocytes, monocytes, neutrophils, eosinophils, hemoglobin. Blood chemistry parameters:sodium, potassium, chloride, glucose, calcium, uric acid, total protein, albumin, creatine phosphokinase, Lipid profile: blood cholesterol,high-density lipoprotein,low-density lipoprotein, and triglycerides,serum follicle-stimulating hormone,Vitamin D,thyroid stimulating hormone,serum pregnancy, HIV/Hepatitis screen,tuberculosis test,alanine aminotransferase,aspartate aminotransferase,Lactate Dehydrogenase,alkaline phosphatase,gamma glutamyl transferase,total bilirubin,blood urea nitrogen,creatinine and bicarbonate. Urinalysis parameters:color,pH,specific gravity,ketones,protein,glucose, bilirubin,nitrite,urobilinogen,occult blood,microscopic examination,urine albumin,beta-2-microglobulin,urine creatinine.
The number of participants with shifts to categorical values of ECG interpretation (e.g. abnormal) were presented by each cohort. Abnormal shift includes a shift from normal or unknown to abnormal.
Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. The criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36 and \> 38 degrees Celsius (C), pulse rate \< 60 and \> 100 beats per minute (bpm), systolic blood pressure (\< 90, \> 140 and \> 160 millimeters of mercury \[mmHg\]), diastolic blood pressure \< 50, \> 90 and \> 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate \< 12 and \> 20 breaths per minute.
The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation, suicidal behavior and non-suicidal self-injurious behavior. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, Suicidal behavior, completed suicide), suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan and intent) and non-suicidal self-injurious behavior.
An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with use of medicinal (investigational) product, whether/not related to medicinal (investigational) product. AE was considered treatment-emergent if it starts or worsens on or after the date of the first dose of study drug in the study until 1 day after the last dose of treatment. SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event. TEAEs included both serious and non-serious TEAEs. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.
Laboratory assessments included hematology, blood chemistry, and urinalysis parameters. Hematology parameters:basophils, hematocrit, red blood cell, total and differential leukocytes, platelets, lymphocytes, monocytes, neutrophils, eosinophils, hemoglobin. Blood chemistry parameters:sodium, potassium, chloride, glucose, calcium, uric acid, total protein, albumin, creatine phosphokinase, Lipid profile: blood cholesterol,high-density lipoprotein,low-density lipoprotein, and triglycerides,serum follicle-stimulating hormone,Vitamin D,thyroid stimulating hormone,serum pregnancy, HIV/Hepatitis screen,tuberculosis test,alanine aminotransferase,aspartate aminotransferase,Lactate Dehydrogenase,alkaline phosphatase,gamma glutamyl transferase,total bilirubin,blood urea nitrogen,creatinine and bicarbonate. Urinalysis parameters:color,pH,specific gravity,ketones,protein,glucose, bilirubin,nitrite,urobilinogen,occult blood,microscopic examination,urine albumin,beta-2-microglobulin,urine creatinine.
The number of participants with shifts to categorical values of ECG interpretation (e.g. abnormal) were presented by each cohort. Abnormal shift includes a shift from normal or unknown to abnormal.
Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. The criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36 and \> 38 degrees C, pulse rate \< 60 and \> 100 bpm, systolic blood pressure (\< 90, \> 140 and \> 160 mmHg), diastolic blood pressure \< 50, \> 90 and \> 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate \< 12 and \> 20 breaths per minute.
The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation, suicidal behavior and non-suicidal self-injurious behavior. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, Suicidal behavior, completed suicide), suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan and intent) and non-suicidal self-injurious behavior.
| Arm | Type | Description |
|---|---|---|
| TP Cohort A | EXPERIMENTAL | Participants weighing ≤ 40 kilograms (kg) will receive DRF 231 milligrams (mg) orally, once daily (QD) (starting dose) on Days 1 to 7 followed by DRF 231 mg orally, BID (twice daily) (maintenance dose) on Day 8 through Week 96. |
| TP Cohort B: Sub-cohort 1: DRF | EXPERIMENTAL | Participants weighing \>40 kg will receive DRF/placebo matching fingolimod 231 mg orally, BID (starting dose) on Days 1 to 7 followed by DRF 462 mg orally, BID (maintenance dose) on Day 8 through Week 96. |
| TP Cohort B: Sub-cohort 1: Fingolimod | EXPERIMENTAL | Participants weighing \>40 kg will receive Fingolimod 0.5 mg orally, QD followed by placebo matching DRF 231 mg (starting dose) orally, BID on Days 1 to 7 followed by placebo matching DRF 462 mg (maintenance dose) orally, BID on Day 8 through Week 96. |
| TP Cohort B: Sub-cohort 2: DMF | EXPERIMENTAL | Participants weighing \>40 kg will receive DMF/placebo matching fingolimod 120 mg (starting dose) orally, BID on Days 1 to 7 followed by DMF 240 mg (maintenance dose) orally BID, on Day 8 through Week 96. |
| TP Cohort B: Sub-cohort 2: Fingolimod | EXPERIMENTAL | Participants weighing \>40 kg will receive Fingolimod 0.5 mg oral QD followed by placebo matching DMF 120 mg (starting dose) orally, BID on Days 1 to 7 followed by placebo matching DMF 240 mg (maintenance dose) orally, BID through Week 96. |
| Open-label Extension (OLE) Period: Participants from Cohort A | EXPERIMENTAL | Participants from Cohort A weighing ≤ 40 kg will receive DRF 231 mg orally, BID and participants weighing \>40 kg will receive DRF 462 mg orally, BID up to 192 weeks. |
| OLE Period: Participants from Cohort B | EXPERIMENTAL | Participants from Cohort B will receive DRF 231 mg orally, BID for 7 days, followed by the maintenance dose of DRF 462 mg orally, BID up to 192 weeks. |
| Diroximel Fumarate (DRF) | EXPERIMENTAL | Japanese and Chinese participants will initiate treatment with DRF 231 milligrams (mg), oral capsule, twice daily on Day 1 through Day 7, followed by DRF 462 mg, oral capsules, twice daily from Day 8 up to Week 48. |
| DRF: Chinese Participants | EXPERIMENTAL | Chinese participants will receive DRF Dose 1, oral capsules, twice daily (BID), from Day 1 to Day 4 and DRF Dose 1, oral capsules, once daily (QD), on Day 5. |
| DRF: Caucasian Participants | EXPERIMENTAL | Caucasian participants will receive DRF Dose 1, oral capsules, BID, from Day 1 to Day 4 and DRF Dose 1, oral capsules, QD, on Day 5. |
| Name | Type | Description |
|---|---|---|
| Diroximel Fumarate | DRUG | Oral capsule |
| Dimethyl Fumarate | DRUG | Oral capsule |
| Fingolimod | DRUG | Oral capsule |
| Placebo matching DRF | DRUG | Oral capsule |
| Placebo matching DMF | DRUG | Oral capsule |
| Placebo matching fingolimod | DRUG | Oral capsule |
Key Inclusion Criteria: Treatment Period: * Must have a diagnosis of pediatric MS (as defined by the revised consensus definition of pediatric MS). * Must have an Expanded Disability Status Scale (EDSS) score between 0 and 5.0, inclusive. * Must have experienced at least 1 of the following conditi...
Diroximel, also known as Diroximel Fumarate, is an investigational small molecule being developed for relapsing forms of multiple sclerosis (RMS). It is also studied in healthy volunteers for pharmacokinetic, safety, and tolerability assessments. The drug is in clinical development and has not been approved for any use.
Diroximel targets KEAP1, a protein involved in cellular stress responses. It acts as an inhibitor of KEAP1, which may modulate pathways relevant to multiple sclerosis. The drug is being investigated for its potential effects in relapsing forms of multiple sclerosis.
Diroximel is being developed by Biogen Inc., a biopharmaceutical company. Biogen's stock ticker is BIIB. The company is conducting clinical trials to evaluate the drug's safety and efficacy in multiple sclerosis and healthy volunteer populations.
Diroximel is in Phase 1 clinical development. While some completed trials have been in Phase 3, the current development stage is Phase 1. The drug is investigational and not yet approved by regulatory authorities. Ongoing studies are evaluating its safety and effects in various populations.
Diroximel has been studied in several trials. NCT05083923, a completed Phase 3 study in adults with relapsing forms of multiple sclerosis, enrolled 136 participants in China and Japan. NCT05127564, a completed Phase 1 study in healthy volunteers, enrolled 32 participants in Hong Kong and New Zealand. NCT07483632, a not-yet-recruiting Phase 3 study in pediatric RMS patients, plans to enroll 185 participants.
Yes, Diroximel is the same as Diroximel Fumarate. The drug is also known by this alternative name. Clinical trials often refer to it as DRF, which stands for Diroximel Fumarate. This compound is being investigated for relapsing forms of multiple sclerosis.