Common Variable Immunodeficiency (CVID), APDS / PASLI
Conditions
Keywords
APDS, PASLI, PI3Kdelta
Brief summary
This study was designed to explore CDZ173, a selective PI3Kδ inhibitor, in patients with genetically activated PI3Kδ, i.e., patients with Activated phosphoinositide 3-kinase delta syndrome/ p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (APDS/PASLI). The study consisted of two parts: Part I was the open label part designed to establish the safety and pharmacokinetics of CDZ173 in the target population, as well as to select the optimal dose to be tested in Part II. Part II was designed to assess efficacy and safety of CDZ173 in the target population.
Detailed description
This was a 2-part (Part I and Part II), Phase 2/3, multi-center study in subjects with APDS/PASLI. Part I of the study was a non-randomized, open-label, within-patient up-titration dose-finding part in 6 participants with APDS/PASLI. The starting dose was 10 mg followed by 30 mg and 70 mg b.i.d. for 4 weeks at each dose level respectively. Part I consisted of three distinct study periods: Screening / Baseline visit (Day -50 to Day-1): This period was used to confirm that the study inclusion and exclusion criteria were met. Participants who were deemed eligible for enrollment into the study attended the clinic on Day -1 for baseline assessments prior to randomization. Treatment period (Day 1 to Day 84): Participants started treatment on Day 1 receiving 10 mg of CDZ173 twice daily (b.i.d.) until Day 28. After a continuous safety review and a review of PK and PD data, participants assessed as satisfactory proceeded to the next dose levels: from Day 29 to Day 56 participants received 30 mg CDZ173 b.i.d. and from Day 57 to Day 84, if assessed as satisfactory, participants received 70 mg CDZ173 b.i.d. Follow-up (Day 85-114): After completion of the treatment period, participants were followed-up for safety for four weeks until Day 114. Part II was a randomized, subject, investigator and sponsor-blinded, placebo-controlled, fixed dose part investigating 31 participants with APDS/PASLI. The CDZ173 dose used in this Part was selected based on safety, tolerability, PK and PD data from Part I. Part II consisted of three distinct study periods: Screening / Baseline visit (Day -50 to Day-1): This period was used to confirm that the study inclusion and exclusion criteria were met. Participants who were deemed eligible for enrollment into the study attended the clinic on Day -1 for baseline assessments prior to randomization. Treatment period (Day 1 to Day 85): On Day 1, Participants were randomized to one of the two treatment groups in a 2:1 ratio to receive either 70 mg CDZ173 b.i.d. or matching placebo until Day 85. Follow-up (Day 86-115): On Day 86, a subset of participants rolled over to CCDZ173X2201E1 extension study and were not followed up for safety after end of treatment in CCDZ173X2201. Participants, who did not directly roll over to the extension study, after last treatment dose were followed-up for safety for four weeks until Day 115.
Interventions
DRUGCDZ173
CDZ173 10 and 70 mg capsules for oral administration.
OTHERPlacebo
Placebo capsules for oral administration
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Part I of the study was a non-randomized, open-label, within-patient up-titration dose-finding part in 6 participants with APDS/PASLI. Part II was a randomized, subject, investigator and sponsor-blinded, placebo-controlled, fixed dose part investigating 31 participants with APDS/PASLI.
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male and female patients 12 to 75 years of age (inclusive), who had a documented APDS/PASLI-associated genetic PI3K delta mutation. * In Part I and Part II, patients must had nodal and/or extranodal lymphoproliferation, and clinical findings and manifestations compatible with APDS/PASLI such as a history of repeated oto-sino-pulmonary infections and/or organ dysfunction (e.g., lung, liver). Additionally, in part II, patients must had at least one measurable nodal lesion on a CT or MRI scan. * At screening, vital signs (systolic and diastolic blood pressure and pulse rate) were assessed in the sitting position after the patient rested for at least three minutes. Key
Exclusion criteria
* Previous or concurrent use of immunosuppressive medication. * Current use of medication known to be strong inhibitor or moderate or strong inducers of isoenzyme CYP3A, if treatment cannot be discontinued or switched to a different medication prior to starting study treatment. * Current use of medications that are metabolized by isoenzyme CYP1A2 and have a narrow therapeutic index (drugs whose exposureresponse indicates that increases in their exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns (e.g., Torsades de Pointes)). * Administration of live vaccines (this includes any attenuated live vaccines) starting from 6 weeks before study entry, during the study and up to 7 days after the last dose of CDZ173. * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study medication and for 2 days after stopping study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 114 days | Number of participants with AEs and SAEs, including significant changes from baseline in physical findings, vital signs, electrocardiograms and laboratory values qualifying and reported as AEs. The number of participants in each category (AEs and SAEs) is reported per dose level: CDZ173 10 mg from Day 1 to Day 28, CDZ173 30 mg from day 29 to day 56 and CDZ173 70 mg from day 57 to day 84. |
| Part I: CDZ173 Dose Concentration | Days 1, 29 and 57 (0.25 and 3 h post morning dose) and Day 84 | Venous whole blood samples were collected for the assessment of the dose-PD and the PK/PD relationship of CDZ173 in participants with APDS/PASLI for dose selection in Part II. CDZ173 was determined by a validated Liquid chromatography - Mass spectometry (LC-MS) method; anticipated Lower Limit of Quantification (LLOQ) was 3 ng/mL. Concentrations below the LLOQ were reported as zero and no methods for imputation of missing data were used. |
| Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | Baseline, days 29 and 57 (3 and 12 h post-dose) and day 84 | Phosphorylation of Akt in ex vivo stimulated and unstimulated B cells was quantified at baseline and at the end of the 4-week treatment period for each of the three dose levels. Determination of the percentage (%) of CD20B+ phospho-Akt positive cells after ex vivo stimulation of whole blood was performed by flow cytometry analysis. The percentage of inhibition of pAkt was defined as (-1) \* percent change from baseline pAkt value. Unstimulated cells served as controls at each time point. Baseline was defined as the mean of the day -1 value and the pre-dose value on Day 1 when both were available (if one was missing, then baseline was defined as the existing value). A higher percentage of inhibition of stimulated B cells indicates improvement. No methods for imputation of missing data were used. |
| Part II: Change From Baseline in the log10 Transformed Sum of Product of Diameters (SPD) in the Index Lesions | Baseline and Day 85 | For the assessment of the impact of CDZ173 on lymphadenopathy, participants were scanned in a magnetic resonance imaging (MRI) or a computed tomography (CT) scanner as based on clinical practice and local regulation. MRI or CT imaging of the neck, chest, abdomen and pelvis was performed. Index lesions were selected from measurable nodal and extranodal lesions as per the Cheson methodology. A maximum of six of the largest dominant lesions were selected and documented at baseline and assessed again at the end of treatment. The change in lymph node size was measured using the log10 transformed sum of product of diameters (SPD), the sum of the longest lesion diameter (mm) and longest perpendicular diameter (mm). A lower score indicates index lesions SPD reduction. A negative change from baseline indicates improvement. |
| Part II: Change From Baseline in Percentage of naïve B Cells Out of Total B Cells | Baseline and Day 85 | APDS/PASLI patients suffer from dysregulation in B cell function and differentiation with low numbers of naive B cells. Change from baseline in percentage of naïve B cells out of total B cells at the end of treatment was assessed by flow cytometry to evaluate the pharmacodynamic effect of CDZ173 on B cell immunophenotyping. A higher percentage in naïve B out of total B cells is a positive outcome. A positive change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part I & II: Physician's Global Assessment (PGA) | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 | In the physician's global assessment questionnaire the Investigator rated the disease activity of their patient using 100 mm Visual analogue Scale (VAS) ranging from no disease activity (0) to maximal disease activity (100). To enhance objectivity, the physician was not aware of the specific patient's global assessment, when performing his own assessment on that patient. No methods for imputation of missing data were used. |
| Part I & II: Patient's Global Assessment (PtGA) | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 | In the patient's global assessment questionnaire patients are asked about their APDS/PASLI related well-being using 100 mm visual analogue scale (VAS) ranging from very poor (0) to very good (100). No methods for imputation of missing data were used. |
| Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Part I: Baseline and Days 1, 15, 29, 57, 84 / Part II: Baseline and Days 1, 15, 29, 57, 85 | High Sensitivity C reactive protein is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. HsCRP was measured in serum using a latex immunochemilunminometric assay (ICMA). No methods for imputation of missing data were used. |
| Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Part I: Baseline and Days 1, 15, 29, 57, 84 / Part II: Baseline and Days 1, 15, 29, 57, 85 | Lactate dehydrogenase is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. LDH was measured in serum using a latex immunochemilunminometric assay (ICMA). No methods for imputation of missing data were used. |
| Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Baseline and Days 1, 15, 29, 57, 85 | Beta2 microglobulin is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. Beta2 microglobulin was measured in serum using a latex immunochemilunminometric assay (ICMA). No methods for imputation of missing data were used. |
| Part I & II: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for CDZ173 | Part I: Days 1, 29 and 57 / Part II: Day 1 | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUClast was calculated from plasma concentration-time data using non-compartmental methods. AUClast was calculated at the first day of every CDZ173 dose level (10, 30 and 70 mg) for Part I and (70 mg) for Part II. No methods for imputation of missing data were used. |
| Part II: Fibrinogen as Biomarker for Systemic Inflammation | Baseline and Days 1, 15, 29, 57, 85 | Fibrinogen is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. Fibrinogen was measured in serum using an Electrochemiluminescence immunoassay (ECLIA). No methods for imputation of missing data were used. |
| Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Baseline and Days 1, 15, 29, 57, 85 | Erythrocyte sedimentation rate (ESR) is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. ESR was measured in whole blood using the Westergren method. No methods for imputation of missing data were used. |
| Part II: 3D Volume of Index Lesions | Baseline and Day 85 | Participants were scanned in a magnetic resonance imaging (MRI) or a computed tomography (CT) scanner as based on clinical practice and local regulation. MRI or CT imaging of the neck, chest, abdomen and pelvis was performed. The 3D volume of index lesions was identified as per the Cheson criteria. A reduction of the 3D volume of the index lesions indicated a positive outcome. |
| Part II: 3D Volume of the Spleen | Baseline and Day 85 | Participants were scanned in a magnetic resonance imaging (MRI) or a computed tomography (CT) scanner as based on clinical practice and local regulation. MRI or CT imaging of the spleen was performed and its 3D volume was identified as per the Cheson criteria. A reduction of the spleen volume indicated a positive outcome. |
| Part II: Ferritin as Biomarker for Systemic Inflammation | Baseline and Days 1, 15, 29, 57, 85 | Ferritin is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. Ferritin was measured in serum using a Electrochemiluminescence immunoassay (ECLIA). No methods for imputation of missing data were used. |
| Part I & II: Maximum Observed Plasma Concentration (Cmax) for CDZ173 | Part I: Days 1, 29 and 57 / Part II: Day 1 | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was calculated from plasma concentration-time data using non-compartmental methods. Cmax was calculated at the first day of every CDZ173 dose level (10, 30 and 70 mg) for Part I and (70 mg) for Part II. No methods for imputation of missing data were used. |
| Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 | The SF-36 is a widely used and extensively studied instrument to measure health-related quality of life (HRQoL) among healthy subjects and patients with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The subscales are aggregated to derive two overall summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores. PCS and MCS scores range from 0 to 100 with a higher score indicating a more favorable health state (range = 0 worst - 100 best). No methods for imputation of missing data were used. |
| Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 | The Work Productivity Activity Impairment (WPAI) questionnaire measures the amount of absence or presence for work attendance and daily work activity impairment attributable to APDS/PASLI. As younger participants (age 12 and above) were enrolled in the study the WPAI-CIQ was used for all participants as it also measures the amount of absence or presence for school attendance and daily classroom activity impairment. Participants responded for classroom or work-related questions depending on their situation. WPAI-CIQ consists of 10 questions that yield 4 types of scores: absenteeism, presenteeism, work/classroom productivity loss and activity impairment. The Overall work impairment due to health (%) score ranges from 0 to 100% with 100% indicating total work impairment and 0% no impairment at all. No methods for imputation of missing data were used. |
| Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 | The Work Productivity Activity Impairment (WPAI) questionnaire measures the amount of absence or presence for work attendance and daily work activity impairment attributable to APDS/PASLI. As younger participants (age 12 and above) were enrolled in the study the WPAI-CIQ was used for all participants as it also measures the amount of absence or presence for school attendance and daily classroom activity impairment. Participants responded for classroom or work-related questions depending on their situation. WPAI-CIQ consists of 10 questions that yield 4 types of scores: absenteeism, presenteeism, work/classroom productivity loss and activity impairment. The Overall classroom impairment due to health (%) score ranges from 0 to 100% with 100% indicating total classroom impairment and 0% no impairment at all. A higher percentage indicates a negative outcome. No methods for imputation of missing data were used. |
Countries
Belarus, Czechia, Germany, Ireland, Italy, Netherlands, Russia, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in 10 investigative sites in 9 countries.
Pre-assignment details
The participants were screened within 50 days prior to enrollment. After screening and baseline assessments, the treatment period started on Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Part I: CDZ173 Participants consecutively received CDZ173 10 mg b.i.d. from Day 1 to Day 28, CDZ173 30 mg b.i.d. from Day 29 to Day 56 and CDZ173 70 mg b.i.d. from Day 57 to Day 84. | 6 |
| Part II: CDZ173 70 mg Participants received CDZ173 70 mg b.i.d. from Day 1 to Day 85. | 21 |
| Part II: Placebo Participants received Placebo b.i.d. from Day 1 to Day 85. | 10 |
| Total | 37 |
Baseline characteristics
| Characteristic | Part I: CDZ173 | Part II: CDZ173 70 mg | Part II: Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 9 Participants | 5 Participants | 16 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 12 Participants | 5 Participants | 21 Participants |
| Age, Continuous | 22.2 Years STANDARD_DEVIATION 5.64 | 22.2 Years STANDARD_DEVIATION 10 | 26.7 Years STANDARD_DEVIATION 13.43 | 23.43 Years STANDARD_DEVIATION 10.44 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 18 Participants | 7 Participants | 31 Participants |
| Sex: Female, Male Female | 2 Participants | 10 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 4 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 21 | 0 / 10 |
| other Total, other adverse events | 2 / 6 | 2 / 6 | 4 / 6 | 4 / 6 | 18 / 21 | 9 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 3 / 21 | 2 / 10 |
Outcome results
Primary
Part I: CDZ173 Dose Concentration
Venous whole blood samples were collected for the assessment of the dose-PD and the PK/PD relationship of CDZ173 in participants with APDS/PASLI for dose selection in Part II. CDZ173 was determined by a validated Liquid chromatography - Mass spectometry (LC-MS) method; anticipated Lower Limit of Quantification (LLOQ) was 3 ng/mL. Concentrations below the LLOQ were reported as zero and no methods for imputation of missing data were used.
Time frame: Days 1, 29 and 57 (0.25 and 3 h post morning dose) and Day 84
Population: All participants enrolled in Part I
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I: CDZ173 Dose Concentration | Day 29: 0.25 h post-dose | 249.00 Nanogram / millilitre | Standard Deviation 540 |
| Part I: CDZ173 10 mg | Part I: CDZ173 Dose Concentration | Day 1: 0.25 h post-dose | 10.10 Nanogram / millilitre | Standard Deviation 1.1 |
| Part I: CDZ173 10 mg | Part I: CDZ173 Dose Concentration | Day 1: 3 h post-dose | 321.00 Nanogram / millilitre | Standard Deviation 115 |
| Part I: CDZ173 10 mg | Part I: CDZ173 Dose Concentration | Day 29: 3 h post-dose | 916.00 Nanogram / millilitre | Standard Deviation 185 |
| Part I: CDZ173 10 mg | Part I: CDZ173 Dose Concentration | Day 57: 0.25 h post-dose | 150.00 Nanogram / millilitre | Standard Deviation 143 |
| Part I: CDZ173 10 mg | Part I: CDZ173 Dose Concentration | Day 57: 3 h post-dose | 1710.00 Nanogram / millilitre | Standard Deviation 782 |
| Part I: CDZ173 10 mg | Part I: CDZ173 Dose Concentration | Day 84 | 998.00 Nanogram / millilitre | Standard Deviation 455 |
Primary
Part II: Change From Baseline in Percentage of naïve B Cells Out of Total B Cells
APDS/PASLI patients suffer from dysregulation in B cell function and differentiation with low numbers of naive B cells. Change from baseline in percentage of naïve B cells out of total B cells at the end of treatment was assessed by flow cytometry to evaluate the pharmacodynamic effect of CDZ173 on B cell immunophenotyping. A higher percentage in naïve B out of total B cells is a positive outcome. A positive change from baseline indicates improvement.
Time frame: Baseline and Day 85
Population: Pharmacodynamic (PD) analysis set. Only participants with a percentage of less than 48% of naive B cells at baseline and with a measured value at Day 85 were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part I: CDZ173 10 mg | Part II: Change From Baseline in Percentage of naïve B Cells Out of Total B Cells | 34.76 Percentage change from baseline | Standard Error 3.08 |
| Part II: Placebo | Part II: Change From Baseline in Percentage of naïve B Cells Out of Total B Cells | -5.37 Percentage change from baseline | Standard Error 3.95 |
p-value: <0.000195% CI: [28.51, 51.75]ANCOVA
Primary
Part II: Change From Baseline in the log10 Transformed Sum of Product of Diameters (SPD) in the Index Lesions
For the assessment of the impact of CDZ173 on lymphadenopathy, participants were scanned in a magnetic resonance imaging (MRI) or a computed tomography (CT) scanner as based on clinical practice and local regulation. MRI or CT imaging of the neck, chest, abdomen and pelvis was performed. Index lesions were selected from measurable nodal and extranodal lesions as per the Cheson methodology. A maximum of six of the largest dominant lesions were selected and documented at baseline and assessed again at the end of treatment. The change in lymph node size was measured using the log10 transformed sum of product of diameters (SPD), the sum of the longest lesion diameter (mm) and longest perpendicular diameter (mm). A lower score indicates index lesions SPD reduction. A negative change from baseline indicates improvement.
Time frame: Baseline and Day 85
Population: Pharmacodynamic (PD) analysis set, excluding participants with 0 lesion at baseline. Only participants with baseline and end of treatment lymphadenopathy measurements were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part I: CDZ173 10 mg | Part II: Change From Baseline in the log10 Transformed Sum of Product of Diameters (SPD) in the Index Lesions | -0.30 Millimeter on Log10 scale | Standard Error 0.04 |
| Part II: Placebo | Part II: Change From Baseline in the log10 Transformed Sum of Product of Diameters (SPD) in the Index Lesions | -0.06 Millimeter on Log10 scale | Standard Error 0.06 |
p-value: 0.001295% CI: [-0.37, -0.11]ANCOVA
Primary
Part I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with AEs and SAEs, including significant changes from baseline in physical findings, vital signs, electrocardiograms and laboratory values qualifying and reported as AEs. The number of participants in each category (AEs and SAEs) is reported per dose level: CDZ173 10 mg from Day 1 to Day 28, CDZ173 30 mg from day 29 to day 56 and CDZ173 70 mg from day 57 to day 84.
Time frame: From the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 114 days
Population: All participants enrolled in Part I.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part I: CDZ173 10 mg | Part I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | CDZ173 10 mg AEs | 2 Participants |
| Part I: CDZ173 10 mg | Part I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | CDZ173 10 mg SAEs | 0 Participants |
| Part I: CDZ173 10 mg | Part I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | CDZ173 30 mg AEs | 2 Participants |
| Part I: CDZ173 10 mg | Part I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | CDZ173 30 mg SAEs | 0 Participants |
| Part I: CDZ173 10 mg | Part I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | CDZ173 70 mg AEs | 4 Participants |
| Part I: CDZ173 10 mg | Part I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | CDZ173 70 mg SAEs | 0 Participants |
Primary
Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells
Phosphorylation of Akt in ex vivo stimulated and unstimulated B cells was quantified at baseline and at the end of the 4-week treatment period for each of the three dose levels. Determination of the percentage (%) of CD20B+ phospho-Akt positive cells after ex vivo stimulation of whole blood was performed by flow cytometry analysis. The percentage of inhibition of pAkt was defined as (-1) \* percent change from baseline pAkt value. Unstimulated cells served as controls at each time point. Baseline was defined as the mean of the day -1 value and the pre-dose value on Day 1 when both were available (if one was missing, then baseline was defined as the existing value). A higher percentage of inhibition of stimulated B cells indicates improvement. No methods for imputation of missing data were used.
Time frame: Baseline, days 29 and 57 (3 and 12 h post-dose) and day 84
Population: All participants who were enrolled in Part I. At each time point, only participants with a derived baseline value and a result at that time point were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Unstimulated: Day 29 - 3 h post-dose | 82.07 Percentage | Standard Deviation 7.25 |
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Stimulated: Day 29 - 3 h post-dose | 78.00 Percentage | Standard Deviation 7.25 |
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Unstimulated: Day 29 - 12 h post-dose | 50.58 Percentage | Standard Deviation 18.73 |
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Stimulated: Day 29 - 12 h post-dose | 47.14 Percentage | Standard Deviation 7.83 |
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Unstimulated: Day 57 - 3 h post-dose | 86.61 Percentage | Standard Deviation 5.26 |
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Stimulated: Day 57 - 3 h post-dose | 60.98 Percentage | Standard Deviation 54.05 |
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Unstimulated: Day 57 - 12 h post-dose | 53.18 Percentage | Standard Deviation 16.59 |
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Stimulated: Day 57 - 12 h post-dose | 63.65 Percentage | Standard Deviation 21.03 |
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Unstimulated: Day 84 | 74.35 Percentage | Standard Deviation 11.03 |
| Part I: CDZ173 10 mg | Part I: Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells | CD20B Stimulated: Day 84 | 78.65 Percentage | Standard Deviation 12 |
Secondary
Part II: 3D Volume of Index Lesions
Participants were scanned in a magnetic resonance imaging (MRI) or a computed tomography (CT) scanner as based on clinical practice and local regulation. MRI or CT imaging of the neck, chest, abdomen and pelvis was performed. The 3D volume of index lesions was identified as per the Cheson criteria. A reduction of the 3D volume of the index lesions indicated a positive outcome.
Time frame: Baseline and Day 85
Population: Pharmacodynamic (PD) analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part II: 3D Volume of Index Lesions | Baseline | 20142.12 Millimeter^3 | Standard Deviation 15617.13 |
| Part I: CDZ173 10 mg | Part II: 3D Volume of Index Lesions | Day 85 | 7858.08 Millimeter^3 | Standard Deviation 6290.98 |
| Part II: Placebo | Part II: 3D Volume of Index Lesions | Baseline | 37123.69 Millimeter^3 | Standard Deviation 67325.94 |
| Part II: Placebo | Part II: 3D Volume of Index Lesions | Day 85 | 40169.28 Millimeter^3 | Standard Deviation 81844.45 |
Secondary
Part II: 3D Volume of the Spleen
Participants were scanned in a magnetic resonance imaging (MRI) or a computed tomography (CT) scanner as based on clinical practice and local regulation. MRI or CT imaging of the spleen was performed and its 3D volume was identified as per the Cheson criteria. A reduction of the spleen volume indicated a positive outcome.
Time frame: Baseline and Day 85
Population: Pharmacodynamic (PD) analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part II: 3D Volume of the Spleen | Baseline | 586448.74 Millimeter^3 | Standard Deviation 311482.61 |
| Part I: CDZ173 10 mg | Part II: 3D Volume of the Spleen | Day 85 | 411130.98 Millimeter^3 | Standard Deviation 193977.46 |
| Part II: Placebo | Part II: 3D Volume of the Spleen | Baseline | 448456.15 Millimeter^3 | Standard Deviation 328641.78 |
| Part II: Placebo | Part II: 3D Volume of the Spleen | Day 85 | 480333.09 Millimeter^3 | Standard Deviation 445371.99 |
Secondary
Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation
Beta2 microglobulin is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. Beta2 microglobulin was measured in serum using a latex immunochemilunminometric assay (ICMA). No methods for imputation of missing data were used.
Time frame: Baseline and Days 1, 15, 29, 57, 85
Population: Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 1 | 2.43 Milligram / liter | Standard Deviation 0.88 |
| Part I: CDZ173 10 mg | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Baseline | 2.46 Milligram / liter | Standard Deviation 0.87 |
| Part I: CDZ173 10 mg | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 15 | 2.10 Milligram / liter | Standard Deviation 1.03 |
| Part I: CDZ173 10 mg | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 29 | 2.02 Milligram / liter | Standard Deviation 1.17 |
| Part I: CDZ173 10 mg | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 57 | 1.90 Milligram / liter | Standard Deviation 0.72 |
| Part I: CDZ173 10 mg | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 85 | 2.01 Milligram / liter | Standard Deviation 1.04 |
| Part II: Placebo | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 57 | 2.42 Milligram / liter | Standard Deviation 1.17 |
| Part II: Placebo | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 29 | 3.21 Milligram / liter | Standard Deviation 1.61 |
| Part II: Placebo | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Baseline | 2.32 Milligram / liter | Standard Deviation 0.96 |
| Part II: Placebo | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 1 | 2.31 Milligram / liter | Standard Deviation 0.95 |
| Part II: Placebo | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 85 | 2.57 Milligram / liter | Standard Deviation 1.19 |
| Part II: Placebo | Part II: Beta2 Microglobulin as Biomarker for Systemic Inflammation | Day 15 | 2.31 Milligram / liter | Standard Deviation 1.09 |
Secondary
Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation
Erythrocyte sedimentation rate (ESR) is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. ESR was measured in whole blood using the Westergren method. No methods for imputation of missing data were used.
Time frame: Baseline and Days 1, 15, 29, 57, 85
Population: Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Baseline | 28.09 Millimeter / hour | Standard Deviation 19.79 |
| Part I: CDZ173 10 mg | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 1 | 26.88 Millimeter / hour | Standard Deviation 19.33 |
| Part I: CDZ173 10 mg | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 15 | 19.50 Millimeter / hour | Standard Deviation 13.52 |
| Part I: CDZ173 10 mg | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 29 | 18.33 Millimeter / hour | Standard Deviation 13.8 |
| Part I: CDZ173 10 mg | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 57 | 18.06 Millimeter / hour | Standard Deviation 15.36 |
| Part I: CDZ173 10 mg | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 85 | 16.35 Millimeter / hour | Standard Deviation 15.99 |
| Part II: Placebo | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 57 | 27.88 Millimeter / hour | Standard Deviation 23.04 |
| Part II: Placebo | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Baseline | 25.44 Millimeter / hour | Standard Deviation 24.88 |
| Part II: Placebo | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 29 | 26.00 Millimeter / hour | Standard Deviation 25.26 |
| Part II: Placebo | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 1 | 25.13 Millimeter / hour | Standard Deviation 24.51 |
| Part II: Placebo | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 85 | 19.63 Millimeter / hour | Standard Deviation 18.03 |
| Part II: Placebo | Part II: Erythrocyte Sedimentation Rate (ESR) as Biomarker for Systemic Inflammation | Day 15 | 16.00 Millimeter / hour | Standard Deviation 12.21 |
Secondary
Part II: Ferritin as Biomarker for Systemic Inflammation
Ferritin is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. Ferritin was measured in serum using a Electrochemiluminescence immunoassay (ECLIA). No methods for imputation of missing data were used.
Time frame: Baseline and Days 1, 15, 29, 57, 85
Population: Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part II: Ferritin as Biomarker for Systemic Inflammation | Baseline | 139.16 Microgram / liter | Standard Deviation 399.73 |
| Part I: CDZ173 10 mg | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 1 | 142.67 Microgram / liter | Standard Deviation 411.57 |
| Part I: CDZ173 10 mg | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 15 | 146.99 Microgram / liter | Standard Deviation 494.88 |
| Part I: CDZ173 10 mg | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 29 | 187.65 Microgram / liter | Standard Deviation 641.16 |
| Part I: CDZ173 10 mg | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 57 | 199.97 Microgram / liter | Standard Deviation 657.31 |
| Part I: CDZ173 10 mg | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 85 | 139.42 Microgram / liter | Standard Deviation 368.68 |
| Part II: Placebo | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 57 | 51.40 Microgram / liter | Standard Deviation 64.95 |
| Part II: Placebo | Part II: Ferritin as Biomarker for Systemic Inflammation | Baseline | 62.05 Microgram / liter | Standard Deviation 81.65 |
| Part II: Placebo | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 29 | 48.43 Microgram / liter | Standard Deviation 61.83 |
| Part II: Placebo | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 1 | 61.34 Microgram / liter | Standard Deviation 82.04 |
| Part II: Placebo | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 85 | 63.16 Microgram / liter | Standard Deviation 56.64 |
| Part II: Placebo | Part II: Ferritin as Biomarker for Systemic Inflammation | Day 15 | 24.61 Microgram / liter | Standard Deviation 17.41 |
Secondary
Part II: Fibrinogen as Biomarker for Systemic Inflammation
Fibrinogen is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. Fibrinogen was measured in serum using an Electrochemiluminescence immunoassay (ECLIA). No methods for imputation of missing data were used.
Time frame: Baseline and Days 1, 15, 29, 57, 85
Population: Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Baseline | 2.66 Gram / liter | Standard Deviation 0.76 |
| Part I: CDZ173 10 mg | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 1 | 2.61 Gram / liter | Standard Deviation 0.81 |
| Part I: CDZ173 10 mg | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 15 | 2.65 Gram / liter | Standard Deviation 0.62 |
| Part I: CDZ173 10 mg | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 29 | 2.53 Gram / liter | Standard Deviation 0.54 |
| Part I: CDZ173 10 mg | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 57 | 3.01 Gram / liter | Standard Deviation 0.68 |
| Part I: CDZ173 10 mg | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 85 | 2.81 Gram / liter | Standard Deviation 0.57 |
| Part II: Placebo | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 57 | 2.83 Gram / liter | Standard Deviation 1.13 |
| Part II: Placebo | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Baseline | 2.68 Gram / liter | Standard Deviation 0.44 |
| Part II: Placebo | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 29 | 2.66 Gram / liter | Standard Deviation 0.58 |
| Part II: Placebo | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 1 | 2.65 Gram / liter | Standard Deviation 0.42 |
| Part II: Placebo | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 85 | 2.61 Gram / liter | Standard Deviation 0.57 |
| Part II: Placebo | Part II: Fibrinogen as Biomarker for Systemic Inflammation | Day 15 | 2.67 Gram / liter | Standard Deviation 0.42 |
Secondary
Part I & II: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for CDZ173
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUClast was calculated from plasma concentration-time data using non-compartmental methods. AUClast was calculated at the first day of every CDZ173 dose level (10, 30 and 70 mg) for Part I and (70 mg) for Part II. No methods for imputation of missing data were used.
Time frame: Part I: Days 1, 29 and 57 / Part II: Day 1
Population: Pharmacokinetics (PK) Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I & II: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for CDZ173 | Day 29 | 4760.0 Hour * nanogram / millilitre | Standard Deviation 816 |
| Part I: CDZ173 10 mg | Part I & II: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for CDZ173 | Day 57 | 10800.0 Hour * nanogram / millilitre | Standard Deviation 3310 |
| Part I: CDZ173 10 mg | Part I & II: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for CDZ173 | Day 1 | 1760.0 Hour * nanogram / millilitre | Standard Deviation 441 |
| Part II: Placebo | Part I & II: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for CDZ173 | Day 1 | 10400.0 Hour * nanogram / millilitre | Standard Deviation 2800 |
Secondary
Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation
High Sensitivity C reactive protein is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. HsCRP was measured in serum using a latex immunochemilunminometric assay (ICMA). No methods for imputation of missing data were used.
Time frame: Part I: Baseline and Days 1, 15, 29, 57, 84 / Part II: Baseline and Days 1, 15, 29, 57, 85
Population: Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at that time point were included (no imputation for missing data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 15 | 0.93 Milligram / liter | Standard Deviation 0.7 |
| Part I: CDZ173 10 mg | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Baseline | 2.49 Milligram / liter | Standard Deviation 1.29 |
| Part I: CDZ173 10 mg | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 29 | 0.77 Milligram / liter | Standard Deviation 0.36 |
| Part I: CDZ173 10 mg | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 84 (Part I) / Day 85 (Part II) | 2.82 Milligram / liter | Standard Deviation 4.11 |
| Part I: CDZ173 10 mg | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 1 | 2.43 Milligram / liter | Standard Deviation 1.43 |
| Part I: CDZ173 10 mg | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 57 | 1.20 Milligram / liter | Standard Deviation 0.71 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 1 | 8.95 Milligram / liter | Standard Deviation 14.56 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Baseline | 10.58 Milligram / liter | Standard Deviation 17.84 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 15 | 9.19 Milligram / liter | Standard Deviation 23.12 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 29 | 5.55 Milligram / liter | Standard Deviation 11.21 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 57 | 6.57 Milligram / liter | Standard Deviation 9.18 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 84 (Part I) / Day 85 (Part II) | 7.54 Milligram / liter | Standard Deviation 18.37 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 1 | 7.85 Milligram / liter | Standard Deviation 4.88 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 84 (Part I) / Day 85 (Part II) | 2.65 Milligram / liter | Standard Deviation 1.79 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 57 | 8.90 Milligram / liter | Standard Deviation 16.66 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 15 | 2.06 Milligram / liter | Standard Deviation 1.02 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Baseline | 5.70 Milligram / liter | Standard Deviation 2.19 |
| Part II: Placebo | Part I & II: High Sensivity C Reactive Protein (hsCRP) as Biomarker for Systemic Inflammation | Day 29 | 2.40 Milligram / liter | Standard Deviation 1.75 |
Secondary
Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation
Lactate dehydrogenase is a blood test biomarker for inflammation in the body. Sequential blood samples were collected in all participants. LDH was measured in serum using a latex immunochemilunminometric assay (ICMA). No methods for imputation of missing data were used.
Time frame: Part I: Baseline and Days 1, 15, 29, 57, 84 / Part II: Baseline and Days 1, 15, 29, 57, 85
Population: Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 15 | 132.17 Units / liter | Standard Deviation 11.44 |
| Part I: CDZ173 10 mg | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Baseline | 130.42 Units / liter | Standard Deviation 18.28 |
| Part I: CDZ173 10 mg | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 29 | 125.17 Units / liter | Standard Deviation 9.85 |
| Part I: CDZ173 10 mg | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 84 (Part I) / Day 85 (Part II) | 142.60 Units / liter | Standard Deviation 18.53 |
| Part I: CDZ173 10 mg | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 1 | 132.17 Units / liter | Standard Deviation 23.1 |
| Part I: CDZ173 10 mg | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 57 | 135.50 Units / liter | Standard Deviation 17.66 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 1 | 170.88 Units / liter | Standard Deviation 72.28 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Baseline | 172.92 Units / liter | Standard Deviation 72.25 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 15 | 190.94 Units / liter | Standard Deviation 71.54 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 29 | 227.17 Units / liter | Standard Deviation 163.41 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 57 | 193.11 Units / liter | Standard Deviation 64.75 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 84 (Part I) / Day 85 (Part II) | 190.63 Units / liter | Standard Deviation 57.62 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 1 | 175.71 Units / liter | Standard Deviation 53.72 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 84 (Part I) / Day 85 (Part II) | 179.13 Units / liter | Standard Deviation 73.96 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 57 | 167.14 Units / liter | Standard Deviation 40.45 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 15 | 155.14 Units / liter | Standard Deviation 48.09 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Baseline | 169.38 Units / liter | Standard Deviation 41.95 |
| Part II: Placebo | Part I & II: Lactate Dehydrogenase (LDH) as Biomarker for Systemic Inflammation | Day 29 | 185.25 Units / liter | Standard Deviation 51.62 |
Secondary
Part I & II: Maximum Observed Plasma Concentration (Cmax) for CDZ173
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was calculated from plasma concentration-time data using non-compartmental methods. Cmax was calculated at the first day of every CDZ173 dose level (10, 30 and 70 mg) for Part I and (70 mg) for Part II. No methods for imputation of missing data were used.
Time frame: Part I: Days 1, 29 and 57 / Part II: Day 1
Population: Pharmacokinetics (PK) Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I & II: Maximum Observed Plasma Concentration (Cmax) for CDZ173 | Day 1 | 393.0 Nanogram / millilitre | Standard Deviation 137 |
| Part I: CDZ173 10 mg | Part I & II: Maximum Observed Plasma Concentration (Cmax) for CDZ173 | Day 29 | 1060.0 Nanogram / millilitre | Standard Deviation 222 |
| Part I: CDZ173 10 mg | Part I & II: Maximum Observed Plasma Concentration (Cmax) for CDZ173 | Day 57 | 2540.0 Nanogram / millilitre | Standard Deviation 747 |
| Part II: Placebo | Part I & II: Maximum Observed Plasma Concentration (Cmax) for CDZ173 | Day 1 | 2150.0 Nanogram / millilitre | Standard Deviation 576 |
Secondary
Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey
The SF-36 is a widely used and extensively studied instrument to measure health-related quality of life (HRQoL) among healthy subjects and patients with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The subscales are aggregated to derive two overall summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores. PCS and MCS scores range from 0 to 100 with a higher score indicating a more favorable health state (range = 0 worst - 100 best). No methods for imputation of missing data were used.
Time frame: Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 84 (Part I) / Day 85 (Part II): Physical Component Summary | 47.54 Score on a scale | Standard Deviation 9.24 |
| Part I: CDZ173 10 mg | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day -1: Mental Component Summary | 47.94 Score on a scale | Standard Deviation 8.22 |
| Part I: CDZ173 10 mg | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 29: Physical Component Summary | 47.54 Score on a scale | Standard Deviation 9.24 |
| Part I: CDZ173 10 mg | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 84 (Part I) / Day 85 (Part II): Mental Component Summary | 47.94 Score on a scale | Standard Deviation 8.22 |
| Part I: CDZ173 10 mg | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day -1: Physical Component Summary | 47.54 Score on a scale | Standard Deviation 9.24 |
| Part I: CDZ173 10 mg | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 57: Mental Component Summary | 47.94 Score on a scale | Standard Deviation 8.22 |
| Part I: CDZ173 10 mg | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 29: Mental Component Summary | 47.94 Score on a scale | Standard Deviation 8.22 |
| Part I: CDZ173 10 mg | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 57: Physical Component Summary | 47.54 Score on a scale | Standard Deviation 9.24 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day -1: Physical Component Summary | 44.49 Score on a scale | Standard Deviation 7.08 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day -1: Mental Component Summary | 47.36 Score on a scale | Standard Deviation 7.98 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 84 (Part I) / Day 85 (Part II): Mental Component Summary | 49.22 Score on a scale | Standard Deviation 8.17 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 84 (Part I) / Day 85 (Part II): Physical Component Summary | 47.59 Score on a scale | Standard Deviation 6.22 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 57: Physical Component Summary | 47.04 Score on a scale | Standard Deviation 7.3 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 29: Mental Component Summary | 49.98 Score on a scale | Standard Deviation 8.06 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 29: Physical Component Summary | 47.87 Score on a scale | Standard Deviation 7.66 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 57: Mental Component Summary | 49.12 Score on a scale | Standard Deviation 8.17 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 84 (Part I) / Day 85 (Part II): Physical Component Summary | 47.48 Score on a scale | Standard Deviation 8.48 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day -1: Mental Component Summary | 45.94 Score on a scale | Standard Deviation 8.14 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day -1: Physical Component Summary | 44.06 Score on a scale | Standard Deviation 8.59 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 29: Mental Component Summary | 49.52 Score on a scale | Standard Deviation 6.7 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 29: Physical Component Summary | 44.62 Score on a scale | Standard Deviation 7.57 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 57: Mental Component Summary | 45.92 Score on a scale | Standard Deviation 7.31 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 57: Physical Component Summary | 47.20 Score on a scale | Standard Deviation 9.75 |
| Part II: Placebo | Part I & II: Mental Component Summary (MCS) and Physical Component Summary (PCS) From Short Form 36 (SF-36) Survey | Day 84 (Part I) / Day 85 (Part II): Mental Component Summary | 47.32 Score on a scale | Standard Deviation 8.73 |
Secondary
Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ)
The Work Productivity Activity Impairment (WPAI) questionnaire measures the amount of absence or presence for work attendance and daily work activity impairment attributable to APDS/PASLI. As younger participants (age 12 and above) were enrolled in the study the WPAI-CIQ was used for all participants as it also measures the amount of absence or presence for school attendance and daily classroom activity impairment. Participants responded for classroom or work-related questions depending on their situation. WPAI-CIQ consists of 10 questions that yield 4 types of scores: absenteeism, presenteeism, work/classroom productivity loss and activity impairment. The Overall classroom impairment due to health (%) score ranges from 0 to 100% with 100% indicating total classroom impairment and 0% no impairment at all. A higher percentage indicates a negative outcome. No methods for imputation of missing data were used.
Time frame: Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85
Population: Pharmacodynamic (PD) analysis set. Only the participants that responded the classroom-related questions from the WPAI-CIQ and with a value at both baseline and that time point were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 57 | 70.13 Percentage | Standard Deviation 18.68 |
| Part I: CDZ173 10 mg | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Baseline | 65.68 Percentage | Standard Deviation 33.49 |
| Part I: CDZ173 10 mg | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 84 (Part I) / Day 85 (Part II) | 68.52 Percentage | Standard Deviation 18.74 |
| Part I: CDZ173 10 mg | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 29 | 57.30 Percentage | Standard Deviation 18.09 |
| Part II: Placebo | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 57 | 12.14 Percentage | Standard Deviation 3.03 |
| Part II: Placebo | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 29 | 0.00 Percentage | Standard Deviation 0 |
| Part II: Placebo | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 84 (Part I) / Day 85 (Part II) | 51.00 Percentage | Standard Deviation 0 |
| Part II: Placebo | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Baseline | 47.33 Percentage | Standard Deviation 44.75 |
| Part II: Placebo | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 84 (Part I) / Day 85 (Part II) | 5.00 Percentage | Standard Deviation 7.07 |
| Part II: Placebo | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Baseline | 23.75 Percentage | Standard Deviation 30.92 |
| Part II: Placebo | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 29 | 22.65 Percentage | Standard Deviation 24.37 |
| Part II: Placebo | Part I & II: Overall Classroom Impairment Due to Health Score From the Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 57 | 22.40 Percentage | Standard Deviation 26.16 |
Secondary
Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ)
The Work Productivity Activity Impairment (WPAI) questionnaire measures the amount of absence or presence for work attendance and daily work activity impairment attributable to APDS/PASLI. As younger participants (age 12 and above) were enrolled in the study the WPAI-CIQ was used for all participants as it also measures the amount of absence or presence for school attendance and daily classroom activity impairment. Participants responded for classroom or work-related questions depending on their situation. WPAI-CIQ consists of 10 questions that yield 4 types of scores: absenteeism, presenteeism, work/classroom productivity loss and activity impairment. The Overall work impairment due to health (%) score ranges from 0 to 100% with 100% indicating total work impairment and 0% no impairment at all. No methods for imputation of missing data were used.
Time frame: Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85
Population: Pharmacodynamic (PD) analysis set. Only the participants that responded the work-related questions from the WPAI-CIQ and with a value at both baseline and that time point were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Baseline | 25.00 Percentage | Standard Deviation 35.36 |
| Part I: CDZ173 10 mg | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 29 | 44.00 Percentage | Standard Deviation 0 |
| Part I: CDZ173 10 mg | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 57 | 62.31 Percentage | Standard Deviation 0 |
| Part I: CDZ173 10 mg | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 84 (Part I) / Day 85 (Part II) | 44.41 Percentage | Standard Deviation 7.9 |
| Part II: Placebo | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 84 (Part I) / Day 85 (Part II) | 35.59 Percentage | Standard Deviation 31.85 |
| Part II: Placebo | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Baseline | 51.25 Percentage | Standard Deviation 37.23 |
| Part II: Placebo | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 57 | 35.49 Percentage | Standard Deviation 24.7 |
| Part II: Placebo | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 29 | 35.31 Percentage | Standard Deviation 23.12 |
| Part II: Placebo | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 84 (Part I) / Day 85 (Part II) | 25.00 Percentage | Standard Deviation 7.07 |
| Part II: Placebo | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 29 | 5.00 Percentage | Standard Deviation 7.07 |
| Part II: Placebo | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Day 57 | 10.00 Percentage | Standard Deviation 14.14 |
| Part II: Placebo | Part I & II: Overall Work Impairment Due to Health Score From Work Productivity Activity Impairment and Classroom Impairment Questionnaire (WPAI-CIQ) | Baseline | 5.00 Percentage | Standard Deviation 7.07 |
Secondary
Part I & II: Patient's Global Assessment (PtGA)
In the patient's global assessment questionnaire patients are asked about their APDS/PASLI related well-being using 100 mm visual analogue scale (VAS) ranging from very poor (0) to very good (100). No methods for imputation of missing data were used.
Time frame: Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I & II: Patient's Global Assessment (PtGA) | Baseline | 62.0 Score on a Scale | Standard Deviation 21.9 |
| Part I: CDZ173 10 mg | Part I & II: Patient's Global Assessment (PtGA) | Day 29 | 65.0 Score on a Scale | Standard Deviation 22.21 |
| Part I: CDZ173 10 mg | Part I & II: Patient's Global Assessment (PtGA) | Day 57 | 67.5 Score on a Scale | Standard Deviation 21.83 |
| Part I: CDZ173 10 mg | Part I & II: Patient's Global Assessment (PtGA) | Day 84 (Part I) / Day 85 (Part II) | 72.5 Score on a Scale | Standard Deviation 13.37 |
| Part II: Placebo | Part I & II: Patient's Global Assessment (PtGA) | Day 84 (Part I) / Day 85 (Part II) | 67.58 Score on a Scale | Standard Deviation 16.57 |
| Part II: Placebo | Part I & II: Patient's Global Assessment (PtGA) | Baseline | 54.53 Score on a Scale | Standard Deviation 21.47 |
| Part II: Placebo | Part I & II: Patient's Global Assessment (PtGA) | Day 57 | 64.79 Score on a Scale | Standard Deviation 19.61 |
| Part II: Placebo | Part I & II: Patient's Global Assessment (PtGA) | Day 29 | 68.37 Score on a Scale | Standard Deviation 19.31 |
| Part II: Placebo | Part I & II: Patient's Global Assessment (PtGA) | Day 84 (Part I) / Day 85 (Part II) | 60.25 Score on a Scale | Standard Deviation 23.66 |
| Part II: Placebo | Part I & II: Patient's Global Assessment (PtGA) | Day 29 | 57.75 Score on a Scale | Standard Deviation 24.03 |
| Part II: Placebo | Part I & II: Patient's Global Assessment (PtGA) | Day 57 | 69.50 Score on a Scale | Standard Deviation 21.93 |
| Part II: Placebo | Part I & II: Patient's Global Assessment (PtGA) | Baseline | 62.50 Score on a Scale | Standard Deviation 26.56 |
Secondary
Part I & II: Physician's Global Assessment (PGA)
In the physician's global assessment questionnaire the Investigator rated the disease activity of their patient using 100 mm Visual analogue Scale (VAS) ranging from no disease activity (0) to maximal disease activity (100). To enhance objectivity, the physician was not aware of the specific patient's global assessment, when performing his own assessment on that patient. No methods for imputation of missing data were used.
Time frame: Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85
Population: Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: CDZ173 10 mg | Part I & II: Physician's Global Assessment (PGA) | Baseline | 34.7 Score on a scale | Standard Deviation 17.07 |
| Part I: CDZ173 10 mg | Part I & II: Physician's Global Assessment (PGA) | Day 29 | 21.8 Score on a scale | Standard Deviation 9.7 |
| Part I: CDZ173 10 mg | Part I & II: Physician's Global Assessment (PGA) | Day 57 | 22.5 Score on a scale | Standard Deviation 13.55 |
| Part I: CDZ173 10 mg | Part I & II: Physician's Global Assessment (PGA) | Day 84 (Part I) / Day 85 (Part II) | 8.8 Score on a scale | Standard Deviation 4.12 |
| Part II: Placebo | Part I & II: Physician's Global Assessment (PGA) | Day 84 (Part I) / Day 85 (Part II) | 26.70 Score on a scale | Standard Deviation 22.82 |
| Part II: Placebo | Part I & II: Physician's Global Assessment (PGA) | Baseline | 47.10 Score on a scale | Standard Deviation 17.65 |
| Part II: Placebo | Part I & II: Physician's Global Assessment (PGA) | Day 57 | 34.02 Score on a scale | Standard Deviation 18.89 |
| Part II: Placebo | Part I & II: Physician's Global Assessment (PGA) | Day 29 | 38.81 Score on a scale | Standard Deviation 23.73 |
| Part II: Placebo | Part I & II: Physician's Global Assessment (PGA) | Day 84 (Part I) / Day 85 (Part II) | 25.88 Score on a scale | Standard Deviation 16.15 |
| Part II: Placebo | Part I & II: Physician's Global Assessment (PGA) | Day 29 | 29.75 Score on a scale | Standard Deviation 9.99 |
| Part II: Placebo | Part I & II: Physician's Global Assessment (PGA) | Day 57 | 24.13 Score on a scale | Standard Deviation 18.34 |
| Part II: Placebo | Part I & II: Physician's Global Assessment (PGA) | Baseline | 41.38 Score on a scale | Standard Deviation 17.78 |