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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-003876-22 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I: CDZ173 | Experimental | Participants consecutively received CDZ173 10 mg twice a day (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. |
|
| Part II: CDZ173 | Experimental | Participants received CDZ173 70 mg b.i.d. from Day 1 to Day 85. |
|
| Part II: Placebo | Placebo Comparator | Participants received Placebo b.i.d. from Day 1 to Day 85. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CDZ173 | Drug | CDZ173 10 and 70 mg capsules for oral administration. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 114 days |
| 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. | Days 1, 29 and 57 (0.25 and 3 h post morning dose) and Day 84 |
| 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. | Baseline, days 29 and 57 (3 and 12 h post-dose) and day 84 |
| Part II: Change From Baseline in the log10 Transformed Sum of Product of Diameters (SPD) in the Index Lesions |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Koneti V Rao, MD | National Institutes of Health (NIH) | Principal Investigator |
| Virgil Dalm, MD | Erasmus Medical Center | Principal Investigator |
| Anna Šedivá, MD | Motol University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institute of Health NIH | Bethesda | Maryland | 20814 | United States | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41091701 | Derived | Upton JEM, Williams KW, Cant A, Santos A, Bana E Costa J, Bradt J, Harrington A, Gwaltney C. Key outcomes in treatment of activated phosphoinositide 3-kinase delta syndrome: An e-Delphi panel study and responder threshold application. PLoS One. 2025 Oct 15;20(10):e0333341. doi: 10.1371/journal.pone.0333341. eCollection 2025. | |
| 36399712 |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novctrd.com | View source |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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The participants were screened within 50 days prior to enrollment. After screening and baseline assessments, the treatment period started on Day 1.
Participants took part in 10 investigative sites in 9 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Part II: CDZ173 70 mg | Participants received CDZ173 70 mg b.i.d. from Day 1 to Day 85. |
| FG002 | Part II: Placebo | Participants received Placebo b.i.d. from Day 1 to Day 85. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Part II: CDZ173 70 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part 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. | All participants enrolled in Part I. | Posted | Count of Participants | Participants | From the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 114 days |
|
Part I and Part II: Adverse events (AEs) were reported from the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 114 days for Part I and 115 days for Part II. For the subset of participants in Part II that rolled over to the extension study (CCDZ173X2201E1) directly after the last treatment dose in Part II, AEs were reported from the start of treatment to end of treatment, assessed up to maximum duration of 85 days.
Any sign or symptom that occurs during the study treatment plus 30 days post treatment. For Part I AEs were reported based on the CDZ173 dose level received when AE started. Therefore, the 30 days post treatment were only applicable for the CDZ173 70 mg arm.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part I: CDZ173 10 mg | Participants received CDZ173 10 mg b.i.d. from Day 1 to Day 28. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (24.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus tachycardia | Cardiac disorders | MedDRA (24.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | + 1 862 778 8300 | Novartis.email@Novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 13, 2020 | Feb 15, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 5, 2022 | Feb 15, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D017074 | Common Variable Immunodeficiency |
| C585640 | Activated PI3K-delta Syndrome |
| ID | Term |
|---|---|
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000625376 | leniolisib |
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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.
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| Placebo | Other | Placebo capsules for oral administration |
|
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. |
| Baseline and Day 85 |
| 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. | Baseline and Day 85 |
| Part I: Days 1, 29 and 57 / Part II: Day 1 |
| 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. | Part I: Days 1, 29 and 57 / Part II: Day 1 |
| 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. | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
| 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. | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
| 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. | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
| 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. | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
| 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. | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
| 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. | Part I: Baseline and Days 1, 15, 29, 57, 84 / Part II: Baseline and Days 1, 15, 29, 57, 85 |
| 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. | Part I: Baseline and Days 1, 15, 29, 57, 84 / Part II: Baseline and Days 1, 15, 29, 57, 85 |
| 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. | Baseline and Days 1, 15, 29, 57, 85 |
| 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. | Baseline and Days 1, 15, 29, 57, 85 |
| 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. | Baseline and Days 1, 15, 29, 57, 85 |
| 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. | Baseline and Days 1, 15, 29, 57, 85 |
| 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. | Baseline and Day 85 |
| 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. | Baseline and Day 85 |
| Minsk |
| 223053 |
| Belarus |
| Novartis Investigative Site | Prague | 150 00 | Czechia |
| Novartis Investigative Site | Dresden | 01307 | Germany |
| Novartis Investigative Site | Dublin | Ireland |
| Novartis Investigative Site | Palermo | PA | 90127 | Italy |
| Novartis Investigative Site | Brescia | 25123 | Italy |
| Novartis Investigative Site | Rotterdam | 3000 CA | Netherlands |
| Novartis Investigative Site | Moscow | 117198 | Russia |
| Novartis Investigative Site | Belfast | BT9 7AB | United Kingdom |
| Rao VK, Webster S, Sediva A, Plebani A, Schuetz C, Shcherbina A, Conlon N, Coulter T, Dalm VA, Trizzino A, Zharankova Y, Kulm E, Korholz J, Lougaris V, Rodina Y, Radford K, Bradt J, Kucher K, Relan A, Holland SM, Lenardo MJ, Uzel G. A randomized, placebo-controlled phase 3 trial of the PI3Kdelta inhibitor leniolisib for activated PI3Kdelta syndrome. Blood. 2023 Mar 2;141(9):971-983. doi: 10.1182/blood.2022018546. |
| 28972011 | Derived | Rao VK, Webster S, Dalm VASH, Sediva A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C. Effective "activated PI3Kdelta syndrome"-targeted therapy with the PI3Kdelta inhibitor leniolisib. Blood. 2017 Nov 23;130(21):2307-2316. doi: 10.1182/blood-2017-08-801191. Epub 2017 Sep 29. |
| A pediatric Plain Language Trial Summary is available on novctrd.com | View source |
Participants received CDZ173 70 mg b.i.d. from Day 1 to Day 85.
| BG002 | Part II: Placebo | Participants received Placebo b.i.d. from Day 1 to Day 85. |
| BG003 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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. | All participants enrolled in Part I | Posted | Mean | Standard Deviation | Nanogram / millilitre | Days 1, 29 and 57 (0.25 and 3 h post morning dose) and Day 84 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Percentage | Baseline, days 29 and 57 (3 and 12 h post-dose) and day 84 |
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| 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. | Pharmacodynamic (PD) analysis set, excluding participants with 0 lesion at baseline. Only participants with baseline and end of treatment lymphadenopathy measurements were included. | Posted | Least Squares Mean | Standard Error | Millimeter on Log10 scale | Baseline and Day 85 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | Percentage change from baseline | Baseline and Day 85 |
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| 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. | Pharmacokinetics (PK) Analysis Set | Posted | Mean | Standard Deviation | Hour * nanogram / millilitre | Part I: Days 1, 29 and 57 / Part II: Day 1 |
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| 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. | Pharmacokinetics (PK) Analysis Set | Posted | Mean | Standard Deviation | Nanogram / millilitre | Part I: Days 1, 29 and 57 / Part II: Day 1 |
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| 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. | Pharmacodynamic (PD) analysis set | Posted | Mean | Standard Deviation | Score on a scale | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Percentage | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Percentage | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
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|
|
| 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. | Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included. | Posted | Mean | Standard Deviation | Score on a scale | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
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|
|
| 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. | Pharmacodynamic (PD) analysis set | Posted | Mean | Standard Deviation | Score on a Scale | Part I: Baseline and Days 29, 57 and 84 / Part II: Baseline and Days 29, 57 and 85 |
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| 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. | Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at that time point were included (no imputation for missing data). | Posted | Mean | Standard Deviation | Milligram / liter | Part I: Baseline and Days 1, 15, 29, 57, 84 / Part II: Baseline and Days 1, 15, 29, 57, 85 |
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|
|
| 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. | Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included. | Posted | Mean | Standard Deviation | Units / liter | Part I: Baseline and Days 1, 15, 29, 57, 84 / Part II: Baseline and Days 1, 15, 29, 57, 85 |
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|
| 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. | Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included. | Posted | Mean | Standard Deviation | Milligram / liter | Baseline and Days 1, 15, 29, 57, 85 |
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|
|
| 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. | Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included. | Posted | Mean | Standard Deviation | Microgram / liter | Baseline and Days 1, 15, 29, 57, 85 |
|
|
|
| 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. | Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included. | Posted | Mean | Standard Deviation | Gram / liter | Baseline and Days 1, 15, 29, 57, 85 |
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|
|
| 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. | Pharmacodynamic (PD) analysis set. At each time point, only participants with a value at both baseline and that time point were included. | Posted | Mean | Standard Deviation | Millimeter / hour | Baseline and Days 1, 15, 29, 57, 85 |
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|
| 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. | Pharmacodynamic (PD) analysis set. | Posted | Mean | Standard Deviation | Millimeter^3 | Baseline and Day 85 |
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|
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| 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. | Pharmacodynamic (PD) analysis set. | Posted | Mean | Standard Deviation | Millimeter^3 | Baseline and Day 85 |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | Part I: CDZ173 30 mg | Participants received CDZ173 30 mg b.i.d. from Day 29 to Day 56. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG002 | Part I: CDZ173 70 mg | Participants received CDZ173 70 mg b.i.d. from Day 57 to Day 84. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG003 | Part I: Total | 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. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG004 | Part II: CDZ173 70 mg | Participants received CDZ173 70 mg b.i.d. from Day 1 to Day 85. | 0 | 21 | 3 | 21 | 18 | 21 |
| EG005 | Part II: Placebo | Participants received Placebo b.i.d. from Day 1 to Day 85. | 0 | 10 | 2 | 10 | 9 | 10 |
| Infective exacerbation of bronchiectasis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Mastoiditis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Coma | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dependence on oxygen therapy | Social circumstances | MedDRA (24.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (24.0) | Systematic Assessment |
|
| Methylenetetrahydrofolate reductase gene mutation | Congenital, familial and genetic disorders | MedDRA (24.0) | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA (24.0) | Systematic Assessment |
|
| External ear pain | Ear and labyrinth disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (24.0) | Systematic Assessment |
|
| Conjunctivitis allergic | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Episcleritis | Eye disorders | MedDRA (24.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vascular device occlusion | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Acute sinusitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Fungal skin infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Groin infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Nasal herpes | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Otitis externa | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Iliotibial band syndrome | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Musculoskeletal injury | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Pancreatic enzymes increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Protein urine present | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| SARS-CoV-2 test positive | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Taste disorder | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA (24.0) | Systematic Assessment |
|
| Anuria | Renal and urinary disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA (24.0) | Systematic Assessment |
|
| Adnexa uteri cyst | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Menstrual disorder | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vasculitis | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Measurements |
|---|---|
|
| Day 29: 3 h post-dose |
|
| Day 57: 0.25 h post-dose |
|
| Day 57: 3 h post-dose |
|
| Day 84 |
|
|
| CD20B Unstimulated: Day 29 - 12 h post-dose |
|
|
| CD20B Stimulated: Day 29 - 12 h post-dose |
|
|
| CD20B Unstimulated: Day 57 - 3 h post-dose |
|
|
| CD20B Stimulated: Day 57 - 3 h post-dose |
|
|
| CD20B Unstimulated: Day 57 - 12 h post-dose |
|
|
| CD20B Stimulated: Day 57 - 12 h post-dose |
|
|
| CD20B Unstimulated: Day 84 |
|
|
| CD20B Stimulated: Day 84 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
|
| Day 29: Mental Component Summary |
|
| Day 29: Physical Component Summary |
|
| Day 57: Mental Component Summary |
|
| Day 57: Physical Component Summary |
|
| Day 84 (Part I) / Day 85 (Part II): Mental Component Summary |
|
| Day 84 (Part I) / Day 85 (Part II): Physical Component Summary |
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 84 (Part I) / Day 85 (Part II) |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 84 (Part I) / Day 85 (Part II) |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 84 (Part I) / Day 85 (Part II) |
|
|
|
| Day 57 |
|
| Day 84 (Part I) / Day 85 (Part II) |
|
| Day 1 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 84 (Part I) / Day 85 (Part II) |
|
|
| Day 1 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 84 (Part I) / Day 85 (Part II) |
|
|
| Day 1 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 1 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 1 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 1 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|