A Study of Diroximel Fumarate (DRF) in Adult Participants... | NCT05083923

Label	Type	Description	Intervention Names
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.	Drug: Diroximel fumarate

Name	Type	Description	Arm Group Labels	Other Names
Diroximel fumarate	Drug	Administered as specified in the treatment arm	Diroximel Fumarate (DRF)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	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.	Baseline (Day 1) up to Week 24 (for prematurely discontinued participants, AEs were reported up to 2 weeks post discontinuation)
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters	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.	Baseline (Day 1) to Week 24
Part 1: Number of Participants With Abnormal Shift in 12-Lead Electrocardiogram (ECG) Values

Secondary Outcomes

Measure	Description	Time Frame
Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set	Summarized data for plasma concentration of MMF at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Must have a diagnosis of RMS, as defined by revised 2017 McDonald's criteria.
Expanded Disability Status Scale (EDSS) score between 0.0 and 5.0, inclusive, at screening and baseline visit (Day 1).
Neurologically stable with no evidence of relapse within 30 days prior to baseline visit (Day 1).
For Japanese participants: Born in Japan and biological parents and grandparents were of Japanese origin. If previously lived outside of Japan for more than 5 years, must not have had a significantly modified diet since leaving Japan.
For Chinese participants: Born in China, and biological parents and grandparents were of Chinese origin. If previously lived outside of China for more than 5 years, must not have had a significantly modified diet since leaving China.

Key Exclusion Criteria:

Has a multiple sclerosis (MS) relapse that has occurred within the 30 days prior to randomization and/or the participant has not stabilized from a previous relapse prior to randomization.
History of severe allergic or anaphylactic reactions or of any allergic reactions that, in the opinion of the investigator, are likely to be exacerbated by any component of the study treatment.
History of, or ongoing, malignant disease, including solid tumors and hematologic malignancies.
Has a history of gastrointestinal (GI) surgery (except appendectomy or cholecystectomy that occurred more than 6 months prior to screening), irritable bowel syndrome, inflammatory bowel disease (Crohn's disease, ulcerative colitis), or other clinically significant and active GI condition per the investigator's discretion.
History of clinically significant recurring or active GI symptoms (e.g., nausea, diarrhea, dyspepsia, constipation) within 90 days of screening, including symptoms that require the initiation of symptomatic medical treatment (e.g., initiation of a medication to treat gastroesophageal reflux disease) or a change in symptomatic medical treatment (e.g., an increase in dose) within 90 days prior to screening.
History of systemic hypersensitivity reaction to DRF, dimethyl fumarate (DMF), MMF or other fumaric esters, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study.
Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days prior to Screening, between screening and baseline visit (Day 1), or at baseline visit (Day 1), including but not limited to a fever (temperature >37.5 degrees Celsius [°C]), new and persistent cough, breathlessness, or loss of taste and/or smell. Evidence of current SARS-CoV-2 infection within 14 days prior to Screening or during Screening, will be eligible for rescreening, provided that the participant is asymptomatic for 14 days prior to rescreening.
Have close contact within 14 days prior to Day 1 with individual(s) with suspected SARS-CoV-2 infection.
For participants who had close contact with individual(s) with suspected SARS-CoV-2 infection within 14 days prior to Day 1, as determined by the Investigator, will be eligible for rescreening, provided that the participant is asymptomatic for 14 days after the contact.
History or positive test result at screening for human immunodeficiency virus (HIV).
Previous participation in this study or previous studies with DRF, DMF, or MMF.
Has a clinically significant history of suicidal ideation or suicidal behavior occurring in the past 12 months as assessed by the C-SSRS at Screening.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Name	Affiliation	Role
Medical Director	Biogen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
The First Affiliated Hospital of Anhui Medical University		Hefei	Anhui	230022	China
Beijing Hospital

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort 1: Japanese Participants	Japanese participants received Diroximel Fumarate (DRF) 231 milligrams (mg), oral capsule, twice daily (BID) on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 23, 2023	Aug 26, 2025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

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.

Safety analysis set included all participants who had received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Baseline (Day 1) up to Week 24 (for prematurely discontinued participants, AEs were reported up to 2 weeks post discontinuation)

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG00052 OG00150

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG00050 OG00145

TESAEs

Title	Measurements
	OG000

Primary

Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters

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.

Safety analysis set included all participants who had received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Baseline (Day 1) to Week 24

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001

Primary

Part 1: Number of Participants With Abnormal Shift in 12-Lead Electrocardiogram (ECG) Values

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.

Safety analysis set included all participants who had received at least 1 dose of study treatment. Here, 'overall number of participants analyzed' signifies the participants who had at least one post baseline value and the baseline value was not abnormal.

Posted

Count of Participants

Participants

Baseline (Day 1) to Week 24

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Primary

Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters

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.

Safety analysis set included all participants who had received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Baseline (Day 1) to Week 24

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Primary

Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events

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.

Safety analysis set included all participants who had received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Baseline (Day 1) to Week 24

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Primary

Parts 1 and 2: Number of Participants With TEAEs and TESAEs

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.

Safety analysis set included all participants who had received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

From Day 1 up to the end of the study (up to Week 50)

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Primary

Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters

Safety analysis set included all participants who had received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Baseline (Day 1) to Week 48

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001

Primary

Part 2: Number of Participants With Abnormal Shift in 12-Lead ECG Values

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.

Posted

Count of Participants

Participants

Baseline (Day 1) to Week 48

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Primary

Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters

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.

Safety analysis set included all participants who had received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Baseline (Day 1) to Week 48

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Primary

Part 2: Number of Participants With C-SSRS Events

Safety analysis set included all participants who had received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Baseline (Day 1) to Week 48

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Secondary

Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set

Summarized data for plasma concentration of MMF at all timepoints is reported.

PK analysis set included all participants who had received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for MMF. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter (ug/mL)

Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG000

Secondary

Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set

Summarized data for plasma concentration of HES at all timepoints is reported.

PK analysis set included all participants who had received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for HES. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.

Posted

Geometric Mean

Geometric Coefficient of Variation

ug/mL

Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG000

Secondary

Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set

PK analysis set was used. Sparse PK set consisted of 49 Japanese participants (including participants from the intensive analysis set, except that sparse PK samples were not collected on the same day as intensive PK sampling) and 48 Chinese participants (total participants in Chinese cohort). Number analysed indicates the number of participants evaluable for the specified timepoint.

Posted

Geometric Mean

Geometric Coefficient of Variation

ug/mL

Pre-dose and 2 to 3 hours post-dose on Day 29 and Day 57

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts

Secondary

Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set

Posted

Geometric Mean

Geometric Coefficient of Variation

ug/mL

Pre-dose and 2 to 3 hours post-dose on Day 29 and Day 57

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
OG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts

Secondary

Part 1: Maximum Observed Concentration (Cmax) of MMF-Intensive PK Analysis Set

Summarized data for Cmax at all timepoints is reported.

PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for MMF. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.

Posted

Geometric Mean

Geometric Coefficient of Variation

ug/mL

Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG000

Secondary

Part 1: Cmax of HES-Intensive PK Analysis Set

Summarized data for Cmax at all timepoints is reported.

PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-dose plasma concentration for HES. The intensive PK analysis set consisted of a subset of participants in the Japanese cohort.

Posted

Geometric Mean

Geometric Coefficient of Variation

ug/mL

Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG000

Secondary

Part 1: Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of MMF-Intensive PK Analysis Set

Summarized data for AUClast at all timepoints is reported.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour*microgram per milliliter (h*ug/mL)

Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG000

Secondary

Part 1: AUClast of HES-Intensive PK Analysis Set

Summarized data for AUClast at all timepoints is reported.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ug/mL

Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG000

Secondary

Part 1: Time to Reach Cmax (Tmax) of MMF-Intensive PK Analysis Set

Summarized data for Tmax at all timepoints is reported.

Posted

Median

Full Range

hours

Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG000

Secondary

Part 1: Tmax of HES-Intensive PK Analysis Set

Summarized data for Tmax at all timepoints is reported.

Posted

Median

Full Range

hours

Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG000

Secondary

Part 1: Elimination Half-Life (t½) of MMF-Intensive PK Analysis Set

Summarized data for t½ at all timepoints is reported.

Posted

Median

Full Range

hours

Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

ID	Title	Description
OG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected50 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected50 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected50 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected50 at risk
Foot deformity	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected50 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected50 at risk
Demyelination	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected50 at risk
Multiple sclerosis relapse	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0013 affected50 at risk
Relapsing-remitting multiple sclerosis	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected50 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected52 at risk EG0013 affected50 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected50 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0002 affected52 at risk EG0013 affected50 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 affected52 at risk EG0015 affected50 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 affected52 at risk EG0012 affected50 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0006 affected52 at risk EG0012 affected50 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 affected52 at risk EG0011 affected50 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00019 affected52 at risk EG0014 affected50 at risk
Faeces soft	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected50 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0005 affected52 at risk EG0013 affected50 at risk
Malaise	General disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected50 at risk
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG0008 affected52 at risk EG0014 affected50 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected50 at risk
Covid-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0009 affected52 at risk EG0015 affected50 at risk
Gastroenteritis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0013 affected50 at risk
Influenza	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0012 affected50 at risk
Nasopharyngitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00011 affected52 at risk EG0012 affected50 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0006 affected52 at risk EG00118 affected50 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 affected52 at risk EG0014 affected50 at risk
Immunisation reaction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0006 affected52 at risk EG0010 affected50 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0006 affected52 at risk EG0015 affected50 at risk
Albumin urine present	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 affected52 at risk EG0013 affected50 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0015 affected50 at risk
Eosinophil count increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected50 at risk
Lymphocyte count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0018 affected50 at risk
Urinary occult blood positive	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected52 at risk EG0014 affected50 at risk
Weight decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected52 at risk EG0016 affected50 at risk
Weight increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected52 at risk EG0013 affected50 at risk
White blood cell count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 affected52 at risk EG0015 affected50 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 affected52 at risk EG0013 affected50 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 affected52 at risk EG0014 affected50 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected50 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected50 at risk
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0012 affected50 at risk
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0006 affected52 at risk EG0015 affected50 at risk
Multiple sclerosis relapse	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0008 affected52 at risk EG0014 affected50 at risk
Paraesthesia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected50 at risk
Depression	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected52 at risk EG0014 affected50 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected50 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected52 at risk EG0015 affected50 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0005 affected52 at risk EG0014 affected50 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected50 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected52 at risk EG0013 affected50 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0013 affected50 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0017 affected50 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 affected52 at risk EG0016 affected50 at risk
Flushing	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG00017 affected52 at risk EG0019 affected50 at risk
Hot flush	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0004 affected52 at risk EG0014 affected50 at risk

ID	Title	Description
BG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
BG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID, on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1: Japanese Participants	Japanese participants received DRF 231 mg, oral capsule, BID on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.	0	52	6	52	50	52
EG001	Cohort 2: Chinese Participants	Chinese participants received DRF 231 mg, oral capsule, BID, on Day 1 through Day 7, followed by DRF 462 (2*231) mg, oral capsules, BID from Day 8 up to Week 48, with allowable dose reduction for tolerability from Day 8 onwards at investigator's discretion.	0	50	6	50	42	50