Systemic Lupus Erythematosus
Conditions
Keywords
Systemic lupus erythematosus
Brief summary
International trial to evaluate the biological activity and safety of cenerimod (ACT-334441) in systemic lupus erythematosus (SLE) patients.
Detailed description
This multicentre, double-blind, placebo-controlled study will have a staggered approach (Part A and B). In part A, eligible patients will be randomly assigned (1:1:1:1) to once daily oral administration of cenerimod (0.5, 1, 2 mg) or placebo. After all patients have completed 4 weeks of treatment during part A, an Independent Data Monitoring Committee will review non-blinded data in an interim analysis to evaluate the safety profile of cenerimod and recommend whether the study could proceed to part B. In part B, additional patients will be randomized (3:1) to once daily oral administration of cenerimod 4 mg or placebo. All participants will receive study medication for 12 weeks.
Interventions
DRUGMatching placebo
One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).
DRUGCenerimod
One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).
Sponsors
Viatris Innovation GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female participants aged 18 to 65 years with established SLE. Participants must have active SLE, Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score of at least 2 points for musculoskeletal or mucocutaneous manifestations and history or presence at screening of positive anti-nuclear antibodies (ANA) or anti-double-stranded DNA (anti-dsDNA) antibodies. * Enrolled participants must be treated with background SLE medications.
Exclusion criteria
* Participants with significant medical conditions or therapies for such conditions (e.g., cardiovascular, pulmonary, immunological, hepatic, ophthalmological, infection and infection risks, history or presence of malignancy, history or presence of bone marrow or solid organ transplantation) or lactating or pregnant women. * Participants with severe SLE disease or with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) | Baseline to end-of-treatment (EOT) (up to 12 weeks) | The primary objective of the clinical study was to asses whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at end-of-treatment (EOT) minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12. |
| Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Baseline, Week 2, Week 4, Week 8, Week 12, end-of-treatment Visit (up to 12 weeks) | The primary objective of the clinical study was to assess whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at visit minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12. |
Countries
Belarus, Bulgaria, Georgia, Russia, Ukraine, United States
Contacts
STUDY_DIRECTORClinical Trials
Viatris Innovation GmbH
Participant flow
Recruitment details
This study was conducted at 18 sites in 6 countries between 1 June 2015 and 28 February 2017, 105 patients signed consent and 67 were randomized to a study treatment: 49 in part A (randomized 1:1:1:1 to receive cenerimod 0.5, 1, 2 mg or placebo) and 18 in part B (randomized 3:1 to receive cenerimod 4 mg or placebo).
Pre-assignment details
The screening period started when the informed consent was signed (up to 30 days before randomization), and ended with randomization. The period included Visit 1 (screening) and the pre-randomization (pre-dose) assessments at Visit 2 (Day 1). Thirty-two patients did not meet the inclusion/exclusion criteria and 6 patients withdrew from the study.
Participants by arm
| Arm | Count |
|---|---|
| Cenerimod 0.5 mg (Part A) Participants received cenerimod 0.5 mg capsules orally once daily for 12 weeks. | 12 |
| Cenerimod 1 mg (Part A) Participants received cenerimod 1 mg capsules orally once daily for 12 weeks. | 12 |
| Cenerimod 2 mg (Part A) Participants received cenerimod 2 mg capsules orally once daily for 12 weeks. | 13 |
| Cenerimod 4 mg (Part B) Participants received cenerimod 4 mg capsules orally once daily for 12 weeks. | 13 |
| Matching Placebo (Part A and Part B) Participants received cenerimod matching placebo capsules orally once daily for 12 weeks. | 17 |
| Total | 67 |
Baseline characteristics
| Characteristic | Cenerimod 1 mg (Part A) | Total | Cenerimod 0.5 mg (Part A) | Matching Placebo (Part A and Part B) | Cenerimod 4 mg (Part B) | Cenerimod 2 mg (Part A) |
|---|---|---|---|---|---|---|
| Age, Continuous Full analysis set | 37.0 years STANDARD_DEVIATION 6.4 | 40.1 years STANDARD_DEVIATION 9.9 | 41.4 years STANDARD_DEVIATION 13.2 | 41.0 years STANDARD_DEVIATION 9.5 | 41.7 years STANDARD_DEVIATION 8.1 | 39.2 years STANDARD_DEVIATION 11.8 |
| Age, Continuous Modified pharmacodynamics analysis set | 38.1 years STANDARD_DEVIATION 5.4 | 40.6 years STANDARD_DEVIATION 9.9 | 41.4 years STANDARD_DEVIATION 13.2 | 41.8 years STANDARD_DEVIATION 9.2 | 41.9 years STANDARD_DEVIATION 8.6 | 39.2 years STANDARD_DEVIATION 11.8 |
| Age, Continuous Pharmacodynamic analysis set | 38.1 years STANDARD_DEVIATION 5.4 | 40.6 years STANDARD_DEVIATION 9.8 | 41.4 years STANDARD_DEVIATION 13.2 | 41.8 years STANDARD_DEVIATION 9.2 | 41.7 years STANDARD_DEVIATION 8.1 | 39.2 years STANDARD_DEVIATION 11.8 |
| Body mass index Full analysis set | 27.4 kg/m^2 STANDARD_DEVIATION 8 | 26.3 kg/m^2 STANDARD_DEVIATION 6 | 25.2 kg/m^2 STANDARD_DEVIATION 5.1 | 25.4 kg/m^2 STANDARD_DEVIATION 6.8 | 27.5 kg/m^2 STANDARD_DEVIATION 4.7 | 26.0 kg/m^2 STANDARD_DEVIATION 5.1 |
| Body mass index Modified pharmacodynamic analysis set | 28.8 kg/m^2 STANDARD_DEVIATION 8.1 | 26.5 kg/m^2 STANDARD_DEVIATION 6.2 | 25.2 kg/m^2 STANDARD_DEVIATION 5.1 | 25.5 kg/m^2 STANDARD_DEVIATION 7 | 28.3 kg/m^2 STANDARD_DEVIATION 5.4 | 26.0 kg/m^2 STANDARD_DEVIATION 5.1 |
| Body mass index Pharmacodynamic analysis set | 28.8 kg/m^2 STANDARD_DEVIATION 8.1 | 26.5 kg/m^2 STANDARD_DEVIATION 6.1 | 25.2 kg/m^2 STANDARD_DEVIATION 5.1 | 25.5 kg/m^2 STANDARD_DEVIATION 7 | 27.5 kg/m^2 STANDARD_DEVIATION 4.7 | 26.0 kg/m^2 STANDARD_DEVIATION 5.1 |
| Disease history time from first Systemic Lupus Erythematosus symptoms Full analysis set | 8.2 years | 6.0 years | 3.7 years | 7.9 years | 4.6 years | 6.7 years |
| Disease history time from first Systemic Lupus Erythematosus symptoms Modified pharmacodynamic analysis set | 9.2 years | 6.2 years | 3.7 years | 7.9 years | 3.2 years | 6.7 years |
| Disease history time from first Systemic Lupus Erythematosus symptoms Pharmacodynamic analysis set | 9.2 years | 6.2 years | 3.7 years | 7.9 years | 4.6 years | 6.7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 67 Participants | 12 Participants | 17 Participants | 13 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of American College of Rheumatology criteria ongoing at screening 0 to 3 ACR criteria more than 6 months ago | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of American College of Rheumatology criteria ongoing at screening 0 to 3 ACR criteria ongoing at screening | 3 Participants | 20 Participants | 5 Participants | 6 Participants | 1 Participants | 5 Participants |
| Number of American College of Rheumatology criteria ongoing at screening 4 to 11 ACR criteria more than 6 months ago | 12 Participants | 67 Participants | 12 Participants | 17 Participants | 13 Participants | 13 Participants |
| Number of American College of Rheumatology criteria ongoing at screening 4 to 11 ACR criteria ongoing at screening | 9 Participants | 47 Participants | 7 Participants | 11 Participants | 12 Participants | 8 Participants |
| Race (NIH/OMB) Full analysis set American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Full analysis set White | 12 Participants | 65 Participants | 12 Participants | 15 Participants | 13 Participants | 13 Participants |
| Race (NIH/OMB) Modified pharmacodynamic analysis set American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Modified pharmacodynamic analysis set Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Modified pharmacodynamic analysis set Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Modified pharmacodynamic analysis set More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Modified pharmacodynamic analysis set Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Modified pharmacodynamic analysis set Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Modified pharmacodynamic analysis set White | 10 Participants | 58 Participants | 12 Participants | 14 Participants | 9 Participants | 13 Participants |
| Race (NIH/OMB) Pharmacodynamic analysis set American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Pharmacodynamic analysis set Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Pharmacodynamic analysis set Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Pharmacodynamic analysis set More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Pharmacodynamic analysis set Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Pharmacodynamic analysis set Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Pharmacodynamic analysis set White | 10 Participants | 62 Participants | 12 Participants | 14 Participants | 13 Participants | 13 Participants |
| Region of Enrollment Belarus | 1 participants | 7 participants | 0 participants | 2 participants | 2 participants | 2 participants |
| Region of Enrollment Bulgaria | 2 participants | 19 participants | 3 participants | 5 participants | 7 participants | 2 participants |
| Region of Enrollment Georgia | 1 participants | 6 participants | 2 participants | 1 participants | 1 participants | 1 participants |
| Region of Enrollment Russia | 6 participants | 22 participants | 3 participants | 5 participants | 2 participants | 6 participants |
| Region of Enrollment Ukraine | 1 participants | 9 participants | 3 participants | 2 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 1 participants | 4 participants | 1 participants | 2 participants | 0 participants | 0 participants |
| Sex: Female, Male Full analysis set Female | 12 Participants | 61 Participants | 11 Participants | 16 Participants | 10 Participants | 12 Participants |
| Sex: Female, Male Full analysis set Male | 0 Participants | 6 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Modified pharmacodynamic analysis set Female | 10 Participants | 56 Participants | 11 Participants | 16 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Modified pharmacodynamic analysis set Male | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Pharmacodynamic analysis set Female | 10 Participants | 59 Participants | 11 Participants | 16 Participants | 10 Participants | 12 Participants |
| Sex: Female, Male Pharmacodynamic analysis set Male | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants |
| Systemic Lupus Erythematosus Disease Activity Index-2000, modified to exclude leucopenia Full analysis set | 8.3 units on a scale STANDARD_DEVIATION 3.7 | 7.7 units on a scale STANDARD_DEVIATION 3.1 | 7.3 units on a scale STANDARD_DEVIATION 3.3 | 7.4 units on a scale STANDARD_DEVIATION 3.3 | 8.7 units on a scale STANDARD_DEVIATION 3.1 | 7.1 units on a scale STANDARD_DEVIATION 2.3 |
| Systemic Lupus Erythematosus Disease Activity Index-2000, modified to exclude leucopenia Modified pharmacodynamic analysis set | 7.0 units on a scale STANDARD_DEVIATION 2.2 | 7.3 units on a scale STANDARD_DEVIATION 2.8 | 7.3 units on a scale STANDARD_DEVIATION 3.3 | 7.3 units on a scale STANDARD_DEVIATION 3.4 | 8.1 units on a scale STANDARD_DEVIATION 2.5 | 7.1 units on a scale STANDARD_DEVIATION 2.3 |
| Systemic Lupus Erythematosus Disease Activity Index-2000, modified to exclude leucopenia Pharmacodynamic analysis set | 7.0 units on a scale STANDARD_DEVIATION 2.2 | 7.5 units on a scale STANDARD_DEVIATION 2.9 | 7.3 units on a scale STANDARD_DEVIATION 3.3 | 7.3 units on a scale STANDARD_DEVIATION 3.4 | 8.7 units on a scale STANDARD_DEVIATION 3.1 | 7.1 units on a scale STANDARD_DEVIATION 2.3 |
| Time from first Systemic Lupus Erythematosus diagnosis Full analysis set | 6.2 years | 3.8 years | 2.4 years | 4.9 years | 2.9 years | 4.5 years |
| Time from first Systemic Lupus Erythematosus diagnosis Modified pharmacodynamic analysis set | 5.8 years | 3.6 years | 2.4 years | 5.0 years | 1.3 years | 4.5 years |
| Time from first Systemic Lupus Erythematosus diagnosis Pharmacodynamic analysis set | 5.8 years | 3.6 years | 2.4 years | 5.0 years | 2.9 years | 4.5 years |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 13 | 0 / 17 |
| other Total, other adverse events | 5 / 12 | 5 / 12 | 6 / 13 | 5 / 13 | 9 / 17 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 13 | 1 / 17 |
Outcome results
Primary
Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment
The primary objective of the clinical study was to assess whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at visit minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12.
Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, end-of-treatment Visit (up to 12 weeks)
Population: Pharmacodynamics analysis (PD) set. The PD set includes all participants who received at least 21 days of study treatment, with lymphocyte count measurements at baseline and post-baseline. Last observation carried forward (using the Week 4 visit or later) was used for participants with a missing end-of-treatment (EOT) assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenerimod 0.5 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | End-of-treatment visit | -0.26 10^9 cells/L | Standard Deviation 0.48 |
| Cenerimod 0.5 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 4 visit | -0.28 10^9 cells/L | Standard Deviation 0.42 |
| Cenerimod 0.5 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 8 Visit | -0.28 10^9 cells/L | Standard Deviation 0.6 |
| Cenerimod 0.5 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 2 visit | -0.13 10^9 cells/L | Standard Deviation 0.56 |
| Cenerimod 0.5 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 12 visit | -0.26 10^9 cells/L | Standard Deviation 0.48 |
| Cenerimod 0.5 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Baseline visit | 1.37 10^9 cells/L | Standard Deviation 0.52 |
| Cenerimod 1 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Baseline visit | 1.71 10^9 cells/L | Standard Deviation 0.82 |
| Cenerimod 1 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 2 visit | -0.48 10^9 cells/L | Standard Deviation 0.56 |
| Cenerimod 1 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 4 visit | -0.69 10^9 cells/L | Standard Deviation 0.76 |
| Cenerimod 1 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 8 Visit | -0.92 10^9 cells/L | Standard Deviation 0.6 |
| Cenerimod 1 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 12 visit | -0.72 10^9 cells/L | Standard Deviation 1.03 |
| Cenerimod 1 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | End-of-treatment visit | -0.72 10^9 cells/L | Standard Deviation 1.03 |
| Cenerimod 2 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 8 Visit | -0.89 10^9 cells/L | Standard Deviation 0.68 |
| Cenerimod 2 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | End-of-treatment visit | -0.86 10^9 cells/L | Standard Deviation 0.61 |
| Cenerimod 2 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 2 visit | -0.52 10^9 cells/L | Standard Deviation 1.03 |
| Cenerimod 2 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Baseline visit | 1.62 10^9 cells/L | Standard Deviation 0.75 |
| Cenerimod 2 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 4 visit | -0.86 10^9 cells/L | Standard Deviation 0.63 |
| Cenerimod 2 mg (Part A) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 12 visit | -0.86 10^9 cells/L | Standard Deviation 0.61 |
| Cenerimod 4 mg (Part B) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 4 visit | -0.68 10^9 cells/L | Standard Deviation 1.32 |
| Cenerimod 4 mg (Part B) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 8 Visit | -1.03 10^9 cells/L | Standard Deviation 1.12 |
| Cenerimod 4 mg (Part B) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 12 visit | -0.87 10^9 cells/L | Standard Deviation 1.24 |
| Cenerimod 4 mg (Part B) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 2 visit | -1.09 10^9 cells/L | Standard Deviation 0.65 |
| Cenerimod 4 mg (Part B) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | End-of-treatment visit | -0.87 10^9 cells/L | Standard Deviation 1.24 |
| Cenerimod 4 mg (Part B) | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Baseline visit | 1.88 10^9 cells/L | Standard Deviation 0.77 |
| Matching Placebo | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | End-of-treatment visit | -0.30 10^9 cells/L | Standard Deviation 0.71 |
| Matching Placebo | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 8 Visit | -0.09 10^9 cells/L | Standard Deviation 0.82 |
| Matching Placebo | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 2 visit | -0.16 10^9 cells/L | Standard Deviation 0.75 |
| Matching Placebo | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 4 visit | -0.33 10^9 cells/L | Standard Deviation 0.69 |
| Matching Placebo | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Week 12 visit | -0.29 10^9 cells/L | Standard Deviation 0.73 |
| Matching Placebo | Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | Baseline visit | 1.65 10^9 cells/L | Standard Deviation 0.88 |
Primary
Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT)
The primary objective of the clinical study was to asses whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at end-of-treatment (EOT) minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12.
Time frame: Baseline to end-of-treatment (EOT) (up to 12 weeks)
Population: Pharmacodynamics analysis (PD) set. The PD set includes all participants who received at least 21 days of study treatment, with lymphocyte count measurements at baseline and post-baseline. Last observation carried forward (using the Week 4 visit or later) was used for participants with a missing end-of-treatment (EOT) assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cenerimod 0.5 mg (Part A) | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) | -0.26 10^9 cells/L | Standard Deviation 0.48 |
| Cenerimod 1 mg (Part A) | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) | -0.96 10^9 cells/L | Standard Deviation 0.68 |
| Cenerimod 2 mg (Part A) | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) | -0.86 10^9 cells/L | Standard Deviation 0.61 |
| Cenerimod 4 mg (Part B) | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) | -0.87 10^9 cells/L | Standard Deviation 1.24 |
| Matching Placebo | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) | -0.33 10^9 cells/L | Standard Deviation 0.72 |
p-value: 0.3995% CI: [-0.56, 0.22]ANCOVA
p-value: 0.0295% CI: [-0.91, 0.09]ANCOVA
p-value: 0.00495% CI: [-0.95, -0.19]ANCOVA
p-value: 0.0695% CI: [-0.75, 0.02]ANCOVA
Post Hoc
Absolute Values of Total Lymphocyte Count at Each Analysis Visit
The primary objective of the clinical study was to see whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The modified pharmacodynamics analysis set includes all participants who: * received at least 21 days of study treatment & * with lymphocyte count measurements at baseline and post-baseline (namely, one sample taken at least 21 days after the first study treatment intake and no later than 7 days after the last study treatment intake with no treatment interruption documented in the first 21 days) & * with cenerimod plasma concentrations at Week 4 consistent with expectations.
Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, end-of-treatment (EOT - up to 12 weeks), end-of-study (6 weeks after EOT)
Population: All participants for which data was available. Ctrough levels were discovered to be low, or below the lower limit of quantification (BLQ), in four patients randomised to the cenerimod 4 mg group, a finding incompatible with compliance with study treatment. These patients were excluded from the PD set to form a modified pharmacodynamic analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cenerimod 0.5 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 8 visit | 1.08 10^9 cells/L | Standard Deviation 0.43 |
| Cenerimod 0.5 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 12 visit | 1.11 10^9 cells/L | Standard Deviation 0.37 |
| Cenerimod 0.5 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 2 visit | 1.24 10^9 cells/L | Standard Deviation 0.34 |
| Cenerimod 0.5 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 4 visit | 1.09 10^9 cells/L | Standard Deviation 0.27 |
| Cenerimod 0.5 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Baseline visit | 1.37 10^9 cells/L | Standard Deviation 0.52 |
| Cenerimod 0.5 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-study visit | 1.42 10^9 cells/L | Standard Deviation 0.37 |
| Cenerimod 0.5 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-treatment visit | 1.11 10^9 cells/L | Standard Deviation 0.37 |
| Cenerimod 1 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-treatment visit | 0.87 10^9 cells/L | Standard Deviation 0.34 |
| Cenerimod 1 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 12 visit | 0.87 10^9 cells/L | Standard Deviation 0.34 |
| Cenerimod 1 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 2 visit | 1.38 10^9 cells/L | Standard Deviation 0.49 |
| Cenerimod 1 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Baseline visit | 1.83 10^9 cells/L | Standard Deviation 0.79 |
| Cenerimod 1 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 4 visit | 0.99 10^9 cells/L | Standard Deviation 0.38 |
| Cenerimod 1 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-study visit | 1.42 10^9 cells/L | Standard Deviation 0.58 |
| Cenerimod 1 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 8 visit | 0.91 10^9 cells/L | Standard Deviation 0.4 |
| Cenerimod 2 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-study visit | 1.35 10^9 cells/L | Standard Deviation 0.45 |
| Cenerimod 2 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Baseline visit | 1.62 10^9 cells/L | Standard Deviation 0.75 |
| Cenerimod 2 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 2 visit | 1.19 10^9 cells/L | Standard Deviation 0.89 |
| Cenerimod 2 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 4 visit | 0.73 10^9 cells/L | Standard Deviation 0.39 |
| Cenerimod 2 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 8 visit | 0.73 10^9 cells/L | Standard Deviation 0.36 |
| Cenerimod 2 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 12 visit | 0.76 10^9 cells/L | Standard Deviation 0.44 |
| Cenerimod 2 mg (Part A) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-treatment visit | 0.76 10^9 cells/L | Standard Deviation 0.44 |
| Cenerimod 4 mg (Part B) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 12 visit | 0.57 10^9 cells/L | Standard Deviation 0.21 |
| Cenerimod 4 mg (Part B) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 8 visit | 0.51 10^9 cells/L | Standard Deviation 0.28 |
| Cenerimod 4 mg (Part B) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Baseline visit | 2.04 10^9 cells/L | Standard Deviation 0.8 |
| Cenerimod 4 mg (Part B) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-treatment visit | 0.57 10^9 cells/L | Standard Deviation 0.21 |
| Cenerimod 4 mg (Part B) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 4 visit | 0.71 10^9 cells/L | Standard Deviation 0.49 |
| Cenerimod 4 mg (Part B) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-study visit | 1.14 10^9 cells/L | Standard Deviation 0.52 |
| Cenerimod 4 mg (Part B) | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 2 visit | 0.79 10^9 cells/L | Standard Deviation 0.44 |
| Matching Placebo | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Baseline visit | 1.66 10^9 cells/L | Standard Deviation 0.91 |
| Matching Placebo | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 12 visit | 1.33 10^9 cells/L | Standard Deviation 0.54 |
| Matching Placebo | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 2 visit | 1.44 10^9 cells/L | Standard Deviation 0.44 |
| Matching Placebo | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 4 visit | 1.31 10^9 cells/L | Standard Deviation 0.5 |
| Matching Placebo | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | Week 8 visit | 1.49 10^9 cells/L | Standard Deviation 0.73 |
| Matching Placebo | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-study visit | 1.71 10^9 cells/L | Standard Deviation 0.86 |
| Matching Placebo | Absolute Values of Total Lymphocyte Count at Each Analysis Visit | End-of-treatment visit | 1.34 10^9 cells/L | Standard Deviation 0.51 |
Post Hoc
Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) Based on Pharmacokinetic Cthrough Profiles
The change was defined as: Total lymphocyte count at end-of-treatment (EOT) minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12. The modified pharmacodynamics analysis set includes all participants who: * received at least 21 days of study treatment & * with lymphocyte count measurements at baseline and post-baseline (namely, one sample taken at least 21 days after the first study treatment intake and no later than 7 days after the last study treatment intake with no treatment interruption documented in the first 21 days) & * with cenerimod plasma concentrations at Week 4 consistent with expectations.
Time frame: Baseline to end-of-treatment (EOT) (up to 12 weeks)
Population: Ctrough levels were discovered to be low, or below the lower limit of quantification (BLQ), in four patients randomized to the cenerimod 4 mg group, a finding incompatible with compliance with study treatment. These patients were excluded from the pharmacodynamic analysis set to form a modified pharmacodynamics analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cenerimod 0.5 mg (Part A) | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) Based on Pharmacokinetic Cthrough Profiles | -0.26 10^9 cells/L | Standard Deviation 0.48 |
| Cenerimod 1 mg (Part A) | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) Based on Pharmacokinetic Cthrough Profiles | -0.96 10^9 cells/L | Standard Deviation 0.68 |
| Cenerimod 2 mg (Part A) | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) Based on Pharmacokinetic Cthrough Profiles | -0.86 10^9 cells/L | Standard Deviation 0.61 |
| Cenerimod 4 mg (Part B) | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) Based on Pharmacokinetic Cthrough Profiles | -1.48 10^9 cells/L | Standard Deviation 0.73 |
| Matching Placebo | Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) Based on Pharmacokinetic Cthrough Profiles | -0.32 10^9 cells/L | Standard Deviation 0.72 |
p-value: 0.283795% CI: [-0.413, 0.123]ANCOVA
p-value: 0.000695% CI: [-0.797, -0.234]ANCOVA
p-value: 0.000195% CI: [-0.825, -0.305]ANCOVA
p-value: <0.000195% CI: [-1.173, -0.586]ANCOVA
Post Hoc
Total Lymphocyte Count Percent Change From Baseline to End-of-treatment (EOT)
Percentage change in total lymphocyte count from baseline to end-of-treatment (EOT). Percent change from baseline is defined as the absolute change from baseline divided by the baseline value (if the baseline value is \> 0) and then multiplied by 100. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The modified pharmacodynamics analysis set includes all participants who: * received at least 21 days of study treatment & * with lymphocyte count measurements at baseline and post-baseline (namely, one sample taken at least 21 days after the first study treatment intake and no later than 7 days after the last study treatment intake with no treatment interruption documented in the first 21 days) & * with cenerimod plasma concentrations at Week 4 consistent with expectations.
Time frame: Baseline to End of Treatment (EOT) (up to 12 weeks)
Population: Ctrough levels were discovered to be low, or below the lower limit of quantification (BLQ), in four patients randomized to the cenerimod 4 mg group, a finding incompatible with compliance with study treatment. These patients were excluded from the pharmacodynamic set to form a modified pharmacodynamic analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cenerimod 0.5 mg (Part A) | Total Lymphocyte Count Percent Change From Baseline to End-of-treatment (EOT) | -12.23 Percent change of total lymphocyte count | Standard Deviation 34.29 |
| Cenerimod 1 mg (Part A) | Total Lymphocyte Count Percent Change From Baseline to End-of-treatment (EOT) | -47.76 Percent change of total lymphocyte count | Standard Deviation 20.37 |
| Cenerimod 2 mg (Part A) | Total Lymphocyte Count Percent Change From Baseline to End-of-treatment (EOT) | -51.52 Percent change of total lymphocyte count | Standard Deviation 22.53 |
| Cenerimod 4 mg (Part B) | Total Lymphocyte Count Percent Change From Baseline to End-of-treatment (EOT) | -69.27 Percent change of total lymphocyte count | Standard Deviation 13.68 |
| Matching Placebo | Total Lymphocyte Count Percent Change From Baseline to End-of-treatment (EOT) | -5.04 Percent change of total lymphocyte count | Standard Deviation 39.22 |
p-value: 0.175595% CI: [-32.513, 6.085]ANCOVA
p-value: 0.000395% CI: [-59.552, -19.069]ANCOVA
p-value: <0.000195% CI: [-65.981, -28.574]ANCOVA
p-value: <0.000195% CI: [-77.585, -35.32]ANCOVA