Amyotrophic Lateral Sclerosis
Conditions
Brief summary
This is a pilot, phase 2, prospective, open-label, single-arm study to evaluate disease progression, forced vital capacity, and the safety and tolerability of plasma exchange (PE) using Albutein® 5% in participants with amyotrophic lateral sclerosis (ALS).
Detailed description
This is a phase 2, prospective, open-label, single-arm pilot study to evaluate the efficacy and safety of PE with Albutein® 5% in participants with ALS. The planned enrollment is 10 participants who have a definite, possible, or probable diagnosis of ALS, according to the revised El Escorial criteria. Enrolled participants will be treated with PE using Albutein 5% as a replacement solution during an Intensive Treatment Phase (2 PEs per week over 3 weeks) followed by a Maintenance Treatment Phase (weekly PE for 21 weeks) for a total treatment duration of 6 months. A 6-month follow up will begin after the last PE.
Interventions
BIOLOGICALAlbutein 5%
Albutein is manufactured from human plasma. The dose of Albutein 5% for replacement following plasma removal will be calculated based on gender, weight, and the hematocrit of the participant.
PROCEDUREPlasma Exchange
Plasma Exchange will be performed using albutein 5% as the replacement solution.
Sponsors
Grifols Biologicals, LLC
Grifols Therapeutics LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Subjects over 18 years of age and less than 70 years old * Subjects with a possible, probable-lab supported, probable, or definite diagnosis of Amyotrophic Lateral Sclerosis (ALS), according to the revised El Escorial criteria * Subjects having experienced their first ALS symptoms within 18 months prior to recruitment/consent * Forced Vital Capacity \> 70% * Subjects must be medically suitable for study participation and willing to comply with all planned aspects of the protocol, including blood sampling, at the time of inclusion in the study.
Exclusion criteria
* Subjects with pre-existing clinically significant lung disease not attributable to ALS * Subjects diagnosed with other neurodegenerative diseases or diseases associated with other motor neuron dysfunction * Participation in another investigational product study within one month prior to screening * Females who are pregnant, breastfeeding, or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/ gel/ film/ cream/ suppository, male sterilization, or true abstinence) throughout the study * Difficult or problematic peripheral vein access and inability to implant a central catheter which would make continuous Plasma exchange (PE) not feasible as per the visit protocol * Contraindication to undergo PE or subject has abnormal coagulation parameters at the discretion of the Outpatient Apheresis Unit team, including but not limited to: 1. Thrombocytopenia (platelets \<100,000/ microliter \[μL\]) 2. Fibrinogen \<1.5 gram per liter (g/L) 3. International Normalized Ratio \>1.5 4. Beta-blocker treatment and bradycardia \<50 beats/min 5. Treatment with angiotensin-converting enzyme inhibitors which may increase the risk of allergic reactions, unless a preventive change in hypotensive treatment occurs prior to enrollment * History of anaphylaxis or severe systemic response to any plasma-derived albumin preparation, component of Albutein® 5%, or other blood product(s) * Subjects unable to interrupt treatment with acetylsalicylic acid, other oral antiplatelet, or anticoagulant * Renal dysfunction by elevated creatinine concentration \>2 milligram per deciliter (mg/dL) * Presence of heart disease that contraindicates PE treatment, including ischemic cardiopathy and congestive heart failure * Presence of prior behavioural disorders requiring pharmacological intervention with less than 3 months of stable treatment * Mentally challenged subject who cannot give independent informed consent * Any condition that would complicate compliance with the study protocol (i.e., illness with the expectation of less than one year survival, abuse of drugs or alcohol, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score | Baseline (Week 0), Weeks 4, 12, 25, 36, and 48 | The ALSFRS-R includes 12 questions to assess the self-sufficiency of participants in 3 sub-domains: bulbar function (questions 1-3), fine and gross motor function (questions 4-9), and respiratory function (question 10-12). Aspects of nourishment, personal care, personal autonomy, and communication were also evaluated. Each task was graded on a five-point scale from 0 (incapable) to 4 (normal ability), with total score range from 0 (worst) to 48 (best). A positive change from Baseline indicates improvement. |
| Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Baseline (Week 0), Weeks 4, 12, 25, 36, and 48 | The FVC measured the volume of air that can forcibly be exhaled through a spirometer after a full inspiration. It was expressed in a percentage of actual FVC over the expected FVC result in the general population, calculated as: Percent predicted FVC (in %) = \[(observed FVC in liters)/(predicted FVC in liters)\]\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cognitive Function as Assessed by Symptom Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test | Baseline (Week 0), Weeks 25, and 48 | ALS-CBS test is composed of two sections: cognitive screening section and behavioural changes section. The section of behavioural changes consists of behaviour status and symptom status sub-scales. Cognitive function assessed by symptom status sub-scale is reported, which consists of 4 additional questions related to current behavioural symptoms (depression, anxiety, fatigue, and emotional liability). Each question was scored as 0= the presence of symptoms and 1= no current symptoms, giving a total subscale score between 0 and 4. A positive change from Baseline indicates improvement. |
| Change From Baseline in Cognitive Function as Assessed by Cognitive Screening Section Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test | Baseline (Week 0), Weeks 25, and 48 | ALS-CBS test is composed of two sections: cognitive screening section and behavioural changes section. Cognitive function is evaluated using cognitive screening section which consists of: attention (complex orders, mental sums, language, and eye movement); concentration (inversion of numeric series); follow-up and monitoring (reverse sequences, alphabet, number and letter sequencing); and initiation and recovery (nomination). The individual items were scored from 0-5, and the total score ranges from 0-20, where 0= cognitive impairment, 20= no apparent cognitive impairment. A positive change from baseline indicates improvement. |
| Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Baseline (Week 0), Weeks 4, 12, 25, 36, and 48 | Surface EMG was performed to record motor evoked potential in the distal muscles of the upper limbs (thenar and hypothenar eminence) and dorsiflexor muscles of the lower limbs (anterior tibialis) after electrical stimulation on the median, ulnar, and external popliteal sciatic nerve. The data for motor evoked potential (in millivolt \[mv\]) is reported for thenar muscles of both upper limbs and hypothenar muscle of the upper right limb and anterior tibialis of the both lower limbs. |
| Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | Weeks 25 and 48 | The ALS questionnaire consists of 40 items grouped into 5 representative dimensions associated with quality of life. The first four dimensions were: physical mobility (questions 1-10), activities of daily living (questions 11- 20), food and drink (questions 21-23), communication (questions 24-30) and emotional function (questions 31-40), refer to deficits and subsequent disabilities as a result of the disease. The fifth scale (emotional functioning) reflects how the participant is facing his/her physical deterioration emotionally. Each item is scored from 0 to 4 according to a gradation of symptom onset frequency (never, rarely, sometimes, often, always). From raw scores, an index from 0 to 100 is obtained for each dimension, which make comparisons with the other dimensions possible as well as a straightforward interpretation of the results (0 = better state of health as measured by the questionnaire;100 = poorer state of health). A negative change from Baseline indicates improvement. |
| Change From Baseline in Plasma Human Apolipoprotein Levels | Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48 | The levels of human Apolipoprotein (ApoE) in plasma were measured by enzyme-linked immunosorbent assay (ELISA). |
| Change From Baseline in Plasma Cytokine Panel Levels | Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48 | The plasma cytokine panel includes: transforming growth factor (TGF) beta1, TGF beta2, TGF beta3, interferon (IFN) gamma, interleukins (IL)-1beta, IL-1Ra, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IFN-γ-inducible protein (IP)-10, human monocyte chemoattractant protein (MCP)-1, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1-alpha, MIP-1-beta, tumor necrosis factor (TNF)-alpha, soluble cluster of differentiation (CD) 40 ligand (sCD40L), fractalkine. The level of each of these cytokines are reported as categories. Only categories with values above the level of detection are reported. |
| Change From Baseline in Cerebrospinal Fluid (CSF) Human Apolipoprotein Levels | Baseline (Week 0), Weeks 12, and 25 | The levels of human Apolipoprotein (ApoE) in CSF were measured by enzyme-linked immunosorbent assay (ELISA). |
| Change From Baseline in Cognitive Function as Assessed by Behaviour Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioural Screen (ALS-CBS) Test | Baseline (Week 0), Weeks 25, and 48 | ALS-CBS test is composed of two sections: the cognitive screening section and behavioural changes section. The section of behavioural changes consists of behaviour status and symptom status sub-scales. Behaviour status sub-scale consists of a questionnaire with 15 items assessed by the caretaker. Each item was scored on a scale ranging from 0 (worst) to 3 (best) yielding a total 0= large changes to 45= no changes. A positive change from Baseline indicates improvement. |
| Change From Baseline in Immune Population Profile | Baseline, Weeks 4, 12, and 48 | The immune population profile includes: Leukocyte panel (neutrophils, lymphocytes, CD14+ monos, CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells, CD56+ NK cells). Regulatory T cells (Treg panel) (CD4+FoxP3+CD127low/, CD4+FoxP3+CD127low/-CD39+, CD4+FoxP3+CD127low/-CD45RA, CD4+FoxP3+CD127low/-CD152+), Myeloid-Derived Suppressor Cells (MDSC) (panel: CD14+CD15- monocytic MDSCs, CD14+CD15- monocytic MDSCs, CD124+ monocytic MDSCs, CD14-CD15+ granulocytic MDSCs, CD124+ granulocytic MDSCs, CD14-CD15- immature MDSCs, CD124+ immature MDSCs), Monocyte panel (CD14+CD16+, CD14+human leukocyte antigen-D related (HLA-DR)+ CD11b, CD14+HLA-DR+ CD163+, CD14+HLA-DR+ CX3CR1+). Data for each of these were reported as categories. Only categories with values above the level of detection are reported. |
| Change From Baseline in Plasma Neurofilament Levels | Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48 | Levels of neurofilaments: Phosphorylated Neurofilament heavy chain (pNF-H) and Neurofilament light chain (NF-L) were measured by Enzyme-Linked Immunosorbent Assay (ELISA). |
| Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels | Baseline (Week 0), Weeks 12, and 25 | Levels of neurofilaments: Phosphorylated Neurofilament heavy chain (pNF-H) and Neurofilament light chain (NF-L) were measured by Enzyme-Linked Immunosorbent Assay (ELISA). |
| Change From Baseline in CSF Cytokine Panel Levels | Baseline (Week 0), Weeks 12, and 25 | The CSF cytokine panel includes: TGF beta1, TGF beta2, TGF beta3, IFN gamma, IL-1beta, IL-1Ra, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IP-10, MCP-1, MDC, MIP-1 alpha, MIP-1 beta, TNF alpha, sCD40L, fractalkine. The level of each of these cytokines are reported as categories. Only categories with values above the level of detection are reported. |
| Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels | Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48 | Plasma BMAA levels at baseline and over the course of treatment at each evaluation visit were measured to identify reductions in BMAA levels, which could potentially be correlated with disease progression or a halt in disease progression. Analysis was performed using a Thermo TSQ Quantiva triple-stage quadrupole mass spectrometer. |
| Change From Cerebrospinal Fluid (CSF) Beta-methylamino-L-alanine (BMAA) Levels | Baseline (Week 0), Weeks 12, and 25 | CSF BMAA levels at baseline and over the course of treatment at each evaluation visit were measured to identify reductions in BMAA levels, which could potentially be correlated with disease progression or a halt in disease progression. Analysis was performed using a Thermo TSQ Quantiva triple quadrupole mass spectrometer. |
| Change From Baseline in Absolute Leukocyte Count | Baseline, Weeks 4, 12, and 48 | The immune population profile in ALS participants was assessed by flow cytometry following whole blood staining by Western Blot (WB) for the absolute leukocyte count. Absolute leukocyte count (10\^3 cells/microliter) was analyzed for neutrophils, lymphocytes, CD14+ monocytes, CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells and CD56+ natural killer (NK) cells. |
Other
| Measure | Time frame |
|---|---|
| Percentage of PE Sessions Associated With at Least One Adverse Reaction (AR) | During or within 72 hours after the completion of the product infusion |
| Percentage of PE Sessions Associated With at Least One Adverse Event (AE), Irrespective of Causality | During or within 72 hours after the completion of the product infusion |
| Incidence of All AEs | Weeks -2 to 48 |
Countries
United States
Participant flow
Recruitment details
Participants took part in this study at a single study center in the Unites States from 29 August 2016 to 15 August 2019.
Pre-assignment details
Participants with diagnosis of amyotrophic lateral sclerosis (ALS) were enrolled to receive plasma exchanges with albutein 5% as a replacement solution as per the protocol defined schedule for 24 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Albutein 5% PEs with albutein 5% as a replacement solution during an intensive treatment phase of two PEs per week over 3 weeks followed by maintenance treatment phase of weekly PE for 21 weeks. The dose of albutein 5% for replacement following plasma removal was calculated based on gender, weight, and the hematocrit of the participant. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | Participant Decision | 3 |
Baseline characteristics
| Characteristic | Albutein 5% |
|---|---|
| Age, Continuous | 59.98 years STANDARD_DEVIATION 7.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 12 |
| other Total, other adverse events | 10 / 12 |
| serious Total, serious adverse events | 2 / 12 |
Outcome results
Primary
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC)
The FVC measured the volume of air that can forcibly be exhaled through a spirometer after a full inspiration. It was expressed in a percentage of actual FVC over the expected FVC result in the general population, calculated as: Percent predicted FVC (in %) = \[(observed FVC in liters)/(predicted FVC in liters)\]\*100.
Time frame: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and a measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Baseline | 89.7 percentage of predicted FVC | Standard Deviation 16.26 |
| Albutein 5% | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Change at Week 4 | -2.6 percentage of predicted FVC | Standard Deviation 4.78 |
| Albutein 5% | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Change at Week 12 | -6.3 percentage of predicted FVC | Standard Deviation 5.5 |
| Albutein 5% | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Change at Week 25 | -13.9 percentage of predicted FVC | Standard Deviation 7.01 |
| Albutein 5% | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Change at Week 36 | -19.4 percentage of predicted FVC | Standard Deviation 12.44 |
| Albutein 5% | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Change at Week 48 | -21.0 percentage of predicted FVC | Standard Deviation 14.83 |
Primary
Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score
The ALSFRS-R includes 12 questions to assess the self-sufficiency of participants in 3 sub-domains: bulbar function (questions 1-3), fine and gross motor function (questions 4-9), and respiratory function (question 10-12). Aspects of nourishment, personal care, personal autonomy, and communication were also evaluated. Each task was graded on a five-point scale from 0 (incapable) to 4 (normal ability), with total score range from 0 (worst) to 48 (best). A positive change from Baseline indicates improvement.
Time frame: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and a measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score | Change at Week 48 | -8.9 units on scale | Standard Deviation 4.74 |
| Albutein 5% | Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score | Baseline | 39.8 units on scale | Standard Deviation 5.88 |
| Albutein 5% | Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score | Change at Week 4 | -1.3 units on scale | Standard Deviation 3.17 |
| Albutein 5% | Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score | Change at Week 12 | -2.5 units on scale | Standard Deviation 1.97 |
| Albutein 5% | Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score | Change at Week 25 | -5.0 units on scale | Standard Deviation 5.03 |
| Albutein 5% | Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score | Change at Week 36 | -9.3 units on scale | Standard Deviation 6.39 |
Secondary
Change From Baseline in Absolute Leukocyte Count
The immune population profile in ALS participants was assessed by flow cytometry following whole blood staining by Western Blot (WB) for the absolute leukocyte count. Absolute leukocyte count (10\^3 cells/microliter) was analyzed for neutrophils, lymphocytes, CD14+ monocytes, CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells and CD56+ natural killer (NK) cells.
Time frame: Baseline, Weeks 4, 12, and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and a measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses of the specific category at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count neutrophils, Baseline | 4.18 10^3 cells/microliter | Standard Deviation 1.359 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count neutrophils, Change at Week 4 | -0.42 10^3 cells/microliter | Standard Deviation 0.828 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count neutrophils, Change at Week 12 | 0.47 10^3 cells/microliter | Standard Deviation 0.732 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count neutrophils, Change at Week 48 | 0.08 10^3 cells/microliter | Standard Deviation 1.731 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count lymphocytes, Baseline | 2.08 10^3 cells/microliter | Standard Deviation 0.881 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count lymphocytes, Change at Week 4 | 0.41 10^3 cells/microliter | Standard Deviation 0.703 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count lymphocytes, Change at Week 12 | 0.38 10^3 cells/microliter | Standard Deviation 1.158 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count lymphocytes, Change at Week 48 | 0.95 10^3 cells/microliter | Standard Deviation 0.914 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD14+ monocytes, Baseline | 0.49 10^3 cells/microliter | Standard Deviation 0.188 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD14+ monocytes, Change at Week 4 | -0.05 10^3 cells/microliter | Standard Deviation 0.157 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD14+ monocytes, Change at Week 12 | 0.07 10^3 cells/microliter | Standard Deviation 0.228 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD14+ monocytes, Change at Week 48 | 0.03 10^3 cells/microliter | Standard Deviation 0.225 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD3+CD4+ T cells, Baseline | 1.01 10^3 cells/microliter | Standard Deviation 0.403 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD3+CD4+ T cells, Change at Week 4 | 0.19 10^3 cells/microliter | Standard Deviation 0.39 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD3+CD4+ T cells, Change at Week12 | 0.27 10^3 cells/microliter | Standard Deviation 0.666 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD3+CD4+ T cells, Change at Week 48 | 0.43 10^3 cells/microliter | Standard Deviation 0.641 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD3+CD8+ T cells, Baseline | 0.38 10^3 cells/microliter | Standard Deviation 0.266 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD3+CD8+ T cells, Change at Week 4 | 0.01 10^3 cells/microliter | Standard Deviation 0.144 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD3+CD8+ T cells, Change at Week 12 | 0.05 10^3 cells/microliter | Standard Deviation 0.242 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD3+CD8+ T cells, Change at Week 48 | 0.13 10^3 cells/microliter | Standard Deviation 0.186 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD19+ B cells, Baseline | 0.07 10^3 cells/microliter | Standard Deviation 0.089 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD19+ B cells, Change at Week 4 | 0.00 10^3 cells/microliter | Standard Deviation 0.043 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD19+ B cells, Change at Week 12 | 0.03 10^3 cells/microliter | Standard Deviation 0.11 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD19+ B cells, Change at Week 48 | 0.00 10^3 cells/microliter | Standard Deviation 0.063 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD56+ NK cells, Baseline | 0.22 10^3 cells/microliter | Standard Deviation 0.127 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD56+ NK cells Change at Week 4 | 0.05 10^3 cells/microliter | Standard Deviation 0.124 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD56+ NK cells, Change at Week 12 | 0.03 10^3 cells/microliter | Standard Deviation 0.101 |
| Albutein 5% | Change From Baseline in Absolute Leukocyte Count | Absolute leukocyte count CD56+ NK cells, Change at Week 48 | 0.07 10^3 cells/microliter | Standard Deviation 0.103 |
Secondary
Change From Baseline in Cerebrospinal Fluid (CSF) Human Apolipoprotein Levels
The levels of human Apolipoprotein (ApoE) in CSF were measured by enzyme-linked immunosorbent assay (ELISA).
Time frame: Baseline (Week 0), Weeks 12, and 25
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and a measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Cerebrospinal Fluid (CSF) Human Apolipoprotein Levels | Baseline | 3877.7 ng/mL | Standard Deviation 1479.73 |
| Albutein 5% | Change From Baseline in Cerebrospinal Fluid (CSF) Human Apolipoprotein Levels | Change at Week 12 | -188.0 ng/mL | Standard Deviation 889.06 |
| Albutein 5% | Change From Baseline in Cerebrospinal Fluid (CSF) Human Apolipoprotein Levels | Change at Week 25 | 20.0 ng/mL | Standard Deviation 743.95 |
Secondary
Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels
Levels of neurofilaments: Phosphorylated Neurofilament heavy chain (pNF-H) and Neurofilament light chain (NF-L) were measured by Enzyme-Linked Immunosorbent Assay (ELISA).
Time frame: Baseline (Week 0), Weeks 12, and 25
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and a measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses for the specific category at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels | pNF-heavy, Baseline | 0.68 ng/mL | Standard Deviation 0.147 |
| Albutein 5% | Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels | pNF-heavy, Change at Week 12 | -0.01 ng/mL | Standard Deviation 0.13 |
| Albutein 5% | Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels | pNF-heavy, Change at Week 25 | 0.07 ng/mL | Standard Deviation 0.16 |
| Albutein 5% | Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels | NF-light, Baseline | 7463.0 ng/mL | Standard Deviation 5857.49 |
| Albutein 5% | Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels | NF-light, Change at Week 12 | 270.6 ng/mL | Standard Deviation 496.12 |
| Albutein 5% | Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels | NF-light, Change at Week 25 | 823.0 ng/mL | Standard Deviation 1137.62 |
Secondary
Change From Baseline in Cognitive Function as Assessed by Behaviour Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioural Screen (ALS-CBS) Test
ALS-CBS test is composed of two sections: the cognitive screening section and behavioural changes section. The section of behavioural changes consists of behaviour status and symptom status sub-scales. Behaviour status sub-scale consists of a questionnaire with 15 items assessed by the caretaker. Each item was scored on a scale ranging from 0 (worst) to 3 (best) yielding a total 0= large changes to 45= no changes. A positive change from Baseline indicates improvement.
Time frame: Baseline (Week 0), Weeks 25, and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Cognitive Function as Assessed by Behaviour Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioural Screen (ALS-CBS) Test | Baseline | 41.7 units on a scale | Standard Deviation 3.44 |
| Albutein 5% | Change From Baseline in Cognitive Function as Assessed by Behaviour Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioural Screen (ALS-CBS) Test | Change at Week 25 | -1.8 units on a scale | Standard Deviation 2.79 |
| Albutein 5% | Change From Baseline in Cognitive Function as Assessed by Behaviour Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioural Screen (ALS-CBS) Test | Change at Week 48 | -8.5 units on a scale | Standard Deviation 5.28 |
Secondary
Change From Baseline in Cognitive Function as Assessed by Cognitive Screening Section Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test
ALS-CBS test is composed of two sections: cognitive screening section and behavioural changes section. Cognitive function is evaluated using cognitive screening section which consists of: attention (complex orders, mental sums, language, and eye movement); concentration (inversion of numeric series); follow-up and monitoring (reverse sequences, alphabet, number and letter sequencing); and initiation and recovery (nomination). The individual items were scored from 0-5, and the total score ranges from 0-20, where 0= cognitive impairment, 20= no apparent cognitive impairment. A positive change from baseline indicates improvement.
Time frame: Baseline (Week 0), Weeks 25, and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Cognitive Function as Assessed by Cognitive Screening Section Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test | Baseline | 16.4 units on scale | Standard Deviation 5.12 |
| Albutein 5% | Change From Baseline in Cognitive Function as Assessed by Cognitive Screening Section Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test | Change at Week 25 | 1.0 units on scale | Standard Deviation 2.76 |
| Albutein 5% | Change From Baseline in Cognitive Function as Assessed by Cognitive Screening Section Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test | Change at Week 48 | 0.8 units on scale | Standard Deviation 2.79 |
Secondary
Change From Baseline in Cognitive Function as Assessed by Symptom Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test
ALS-CBS test is composed of two sections: cognitive screening section and behavioural changes section. The section of behavioural changes consists of behaviour status and symptom status sub-scales. Cognitive function assessed by symptom status sub-scale is reported, which consists of 4 additional questions related to current behavioural symptoms (depression, anxiety, fatigue, and emotional liability). Each question was scored as 0= the presence of symptoms and 1= no current symptoms, giving a total subscale score between 0 and 4. A positive change from Baseline indicates improvement.
Time frame: Baseline (Week 0), Weeks 25, and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Cognitive Function as Assessed by Symptom Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test | Baseline | 3.5 units on scale | Standard Deviation 0.69 |
| Albutein 5% | Change From Baseline in Cognitive Function as Assessed by Symptom Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test | Change at Week 25 | -0.2 units on scale | Standard Deviation 0.75 |
| Albutein 5% | Change From Baseline in Cognitive Function as Assessed by Symptom Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test | Change at Week 48 | -0.2 units on scale | Standard Deviation 1.33 |
Secondary
Change From Baseline in CSF Cytokine Panel Levels
The CSF cytokine panel includes: TGF beta1, TGF beta2, TGF beta3, IFN gamma, IL-1beta, IL-1Ra, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IP-10, MCP-1, MDC, MIP-1 alpha, MIP-1 beta, TNF alpha, sCD40L, fractalkine. The level of each of these cytokines are reported as categories. Only categories with values above the level of detection are reported.
Time frame: Baseline (Week 0), Weeks 12, and 25
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with detectable values for the analyses of the specific category at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | TGF beta2; Baseline | 224.73 pg/mL | Standard Deviation 36.83 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | TGF beta2; Change at Week 12 | -8.38 pg/mL | Standard Deviation 27.358 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | TGF beta2; Change at Week 25 | 4.24 pg/mL | Standard Deviation 26.517 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IL-1Ra; Baseline | 11.20 pg/mL | — |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IL-8; Baseline | 28.71 pg/mL | Standard Deviation 6.575 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IL-8; Change at Week 12 | -0.30 pg/mL | Standard Deviation 4.323 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IL-8; Change at Week 25 | 2.11 pg/mL | Standard Deviation 5.498 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IL-12 p70; Baseline | 3.80 pg/mL | — |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IL-17A; Baseline | 20.16 pg/mL | Standard Deviation 4.87 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IL-17A; Change at Week 12 | -0.84 pg/mL | Standard Deviation 3.211 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IL-17A; Change at Week 25 | -2.61 pg/mL | Standard Deviation 5.591 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IP-10; Baseline | 493.6 pg/mL | Standard Deviation 239.39 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IP-10; Change at Week 12 | -38.4 pg/mL | Standard Deviation 99.46 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | IP-10; Change at Week 25 | -30.6 pg/mL | Standard Deviation 218.26 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | MCP-1; Baseline | 1325.7 pg/mL | Standard Deviation 331.09 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | MCP-1; Change at Week 12 | -80.6 pg/mL | Standard Deviation 169.01 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | MCP-1; Change at Week 25 | 30.5 pg/mL | Standard Deviation 235.17 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | MDC; Baseline | 9.70 pg/mL | Standard Deviation 2.97 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | MDC; Change at Week 12 | 0.00 pg/mL | — |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | MIP-1 beta; Baseline | 13.95 pg/mL | Standard Deviation 4.555 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | MIP-1 beta; Change at Week 12 | 0.18 pg/mL | Standard Deviation 3.393 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | MIP-1 beta; Change at Week 25 | -0.44 pg/mL | Standard Deviation 3.054 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | TNF alpha; Baseline | 3.83 pg/mL | Standard Deviation 1.809 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | TNF alpha; Change at Week 12 | 0.40 pg/mL | Standard Deviation 1.717 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | TNF alpha; Change at Week 25 | -0.85 pg/mL | Standard Deviation 1.731 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | sCD40L; Baseline | 4.13 pg/mL | Standard Deviation 2.955 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | sCD40L; Change at Week 12 | -5.50 pg/mL | — |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | sCD40L; Change at Week 25 | 1.80 pg/mL | — |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | Fractalkine; Baseline | 16.17 pg/mL | Standard Deviation 8.776 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | Fractalkine; Change at Week 12 | 0.00 pg/mL | Standard Deviation 0 |
| Albutein 5% | Change From Baseline in CSF Cytokine Panel Levels | Fractalkine; Change at Week 25 | 0.00 pg/mL | Standard Deviation 0 |
Secondary
Change From Baseline in Immune Population Profile
The immune population profile includes: Leukocyte panel (neutrophils, lymphocytes, CD14+ monos, CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells, CD56+ NK cells). Regulatory T cells (Treg panel) (CD4+FoxP3+CD127low/, CD4+FoxP3+CD127low/-CD39+, CD4+FoxP3+CD127low/-CD45RA, CD4+FoxP3+CD127low/-CD152+), Myeloid-Derived Suppressor Cells (MDSC) (panel: CD14+CD15- monocytic MDSCs, CD14+CD15- monocytic MDSCs, CD124+ monocytic MDSCs, CD14-CD15+ granulocytic MDSCs, CD124+ granulocytic MDSCs, CD14-CD15- immature MDSCs, CD124+ immature MDSCs), Monocyte panel (CD14+CD16+, CD14+human leukocyte antigen-D related (HLA-DR)+ CD11b, CD14+HLA-DR+ CD163+, CD14+HLA-DR+ CX3CR1+). Data for each of these were reported as categories. Only categories with values above the level of detection are reported.
Time frame: Baseline, Weeks 4, 12, and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and a measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with detectable values for analyses of the specific category at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: neutrophils; Baseline | 68.13 percentage of CD45+ cells | Standard Deviation 11.672 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: neutrophils; Change at Week 4 | -6.58 percentage of CD45+ cells | Standard Deviation 9.457 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: neutrophils; Change at Week 12 | -0.26 percentage of CD45+ cells | Standard Deviation 12.391 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: neutrophils; Change at Week 48 | -10.08 percentage of CD45+ cells | Standard Deviation 13.188 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: lymphocytes; Baseline | 23.48 percentage of CD45+ cells | Standard Deviation 11.681 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: lymphocytes; Change at Week 4 | 7.12 percentage of CD45+ cells | Standard Deviation 10.026 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: lymphocytes; Change at Week 12 | 1.17 percentage of CD45+ cells | Standard Deviation 10.531 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: lymphocytes; Change at Week 48 | 11.94 percentage of CD45+ cells | Standard Deviation 15.553 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD14+ monos; Baseline | 6.49 percentage of CD45+ cells | Standard Deviation 1.832 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD14+ monos; Change at Week 4 | -0.92 percentage of CD45+ cells | Standard Deviation 2.592 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD14+ monos; Change at Week 12 | -0.31 percentage of CD45+ cells | Standard Deviation 2.329 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD14+ monos; Change at Week 48 | 0.34 percentage of CD45+ cells | Standard Deviation 3.424 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD3+CD4+ T cells; Baseline | 11.58 percentage of CD45+ cells | Standard Deviation 6.274 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD3+CD4+ T cells; Change at Week 4 | 4.77 percentage of CD45+ cells | Standard Deviation 5.956 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD3+CD4+ T cells; Change at Week 12 | 0.17 percentage of CD45+ cells | Standard Deviation 7.23 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD3+CD4+ T cells; Change at Week 48 | 5.46 percentage of CD45+ cells | Standard Deviation 10.954 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD3+CD8+ T cells; Baseline | 3.71 percentage of CD45+ cells | Standard Deviation 2.473 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD3+CD8+ T cells; Change at Week 4 | 1.12 percentage of CD45+ cells | Standard Deviation 1.529 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD3+CD8+ T cells; Change at Week 12 | 0.14 percentage of CD45+ cells | Standard Deviation 1.303 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD3+CD8+ T cells; Change at Week 48 | 1.64 percentage of CD45+ cells | Standard Deviation 3.179 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD19+ B cells; Baseline | 2.12 percentage of CD45+ cells | Standard Deviation 1.312 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD19+ B cells; Change at Week 4 | 1.06 percentage of CD45+ cells | Standard Deviation 1.42 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD19+ B cells; Change at Week 12 | 0.56 percentage of CD45+ cells | Standard Deviation 1.24 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD19+ B cells; Change at Week 48 | 1.88 percentage of CD45+ cells | Standard Deviation 1.931 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD56+ NK cells; Baseline | 3.80 percentage of CD45+ cells | Standard Deviation 2.61 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD56+ NK cells; Change at Week 4 | -0.04 percentage of CD45+ cells | Standard Deviation 1.417 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD56+ NK cells; Change at Week 12 | -0.17 percentage of CD45+ cells | Standard Deviation 2.051 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Leukocyte panel: CD56+ NK cells; Change at Week 48 | 0.92 percentage of CD45+ cells | Standard Deviation 4.419 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Regulatory T cells (Treg panel): CD4+FoxP3+CD127low/-; Baseline | 0.5717 percentage of CD45+ cells | Standard Deviation 0.40475 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-; Change at Week 4 | -0.0267 percentage of CD45+ cells | Standard Deviation 0.21641 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-; Change at Week 12 | -0.1648 percentage of CD45+ cells | Standard Deviation 0.41184 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-; Change at Week 48 | -0.0658 percentage of CD45+ cells | Standard Deviation 0.35043 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD39+; Baseline | 0.1196 percentage of CD45+ cells | Standard Deviation 0.08932 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD39+; Change at Week 4 | 0.1845 percentage of CD45+ cells | Standard Deviation 0.10536 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD39+; Change at Week 12 | -0.1300 percentage of CD45+ cells | — |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD39+; Change at Week 48 | -0.0850 percentage of CD45+ cells | Standard Deviation 0.25314 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD45RA; Baseline | 0.4953 percentage of CD45+ cells | Standard Deviation 0.3412 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD45RA; Change at Week 4 | 0.6278 percentage of CD45+ cells | Standard Deviation 2.17115 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD45RA; Change at Week 12 | -0.1296 percentage of CD45+ cells | Standard Deviation 0.34452 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD45RA; Change at Week 48 | -0.0420 percentage of CD45+ cells | Standard Deviation 0.29646 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD152+; Baseline | 0.2028 percentage of CD45+ cells | Standard Deviation 0.17937 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD152+; Change at Week 4 | -0.0282 percentage of CD45+ cells | Standard Deviation 0.10316 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD152+; Change at Week 12 | -0.1100 percentage of CD45+ cells | Standard Deviation 0.16162 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Treg panel: CD4+FoxP3+CD127low/-CD152+; Change at Week 48 | 0.0490 percentage of CD45+ cells | Standard Deviation 0.32648 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Myeloid-Derived Suppressor Cells (MDSC) panel: CD14+CD15- monocytic MDSCs; Baseline | 0.3207 percentage of CD45+ cells | Standard Deviation 0.25371 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Myeloid-Derived Suppressor Cells (MDSC) panel: CD14+CD15- monocytic MDSCs; Change at Week 4 | -0.1061 percentage of CD45+ cells | Standard Deviation 0.22023 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Myeloid-Derived Suppressor Cells (MDSC) panel: CD14+CD15- monocytic MDSCs; Change at Week 12 | -0.1005 percentage of CD45+ cells | Standard Deviation 0.2583 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Myeloid-Derived Suppressor Cells (MDSC) panel: CD14+CD15- monocytic MDSCs; Change at Week 48 | -0.3650 percentage of CD45+ cells | Standard Deviation 0.4103 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ monocytic MDSCs; Baseline | 0.1525 percentage of CD45+ cells | Standard Deviation 0.10414 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ monocytic MDSCs; Change at Week 4 | -0.0536 percentage of CD45+ cells | Standard Deviation 0.09398 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ monocytic MDSCs; Change at Week 12 | -0.0816 percentage of CD45+ cells | Standard Deviation 0.18479 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ monocytic MDSCs; Change at Week 48 | -0.1308 percentage of CD45+ cells | Standard Deviation 0.03511 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD14-CD15+ granulocytic MDSCs; Baseline | 0.3258 percentage of CD45+ cells | Standard Deviation 0.36484 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD14-CD15+ granulocytic MDSCs; Change at Week 4 | -0.0775 percentage of CD45+ cells | Standard Deviation 0.30306 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD14-CD15+ granulocytic MDSCs; Change at Week 12 | -0.1336 percentage of CD45+ cells | Standard Deviation 0.45262 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD14-CD15+ granulocytic MDSCs; Change at Week 48 | -0.0556 percentage of CD45+ cells | Standard Deviation 0.34335 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ granulocytic MDSCs; Baseline | 0.1689 percentage of CD45+ cells | Standard Deviation 0.27247 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ granulocytic MDSCs; Change at Week 4 | -0.1310 percentage of CD45+ cells | Standard Deviation 0.33046 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ granulocytic MDSCs; Change at Week 12 | -0.2081 percentage of CD45+ cells | Standard Deviation 0.39793 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ granulocytic MDSCs; Change at Week 48 | 0.0380 percentage of CD45+ cells | — |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD14-CD15- immature MDSCs; Baseline | 0.2442 percentage of CD45+ cells | Standard Deviation 0.20666 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD14-CD15- immature MDSCs; Change at Week 4 | -0.0161 percentage of CD45+ cells | Standard Deviation 0.21032 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD14-CD15- immature MDSCs; Change at Week 12 | -0.1297 percentage of CD45+ cells | Standard Deviation 0.18064 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD14-CD15- immature MDSCs; Change at Week 48 | -0.0768 percentage of CD45+ cells | Standard Deviation 0.13691 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ immature MDSCs; Baseline | 0.1011 percentage of CD45+ cells | Standard Deviation 0.06344 |
| Albutein 5% | Change From Baseline in Immune Population Profile | MDSC panel: CD124+ immature MDSCs; Change at Week 4 | -0.0853 percentage of CD45+ cells | Standard Deviation 0.02369 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+CD16+; Baseline | 0.4317 percentage of CD45+ cells | Standard Deviation 0.37154 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+CD16+; Change at Week 4 | -0.2408 percentage of CD45+ cells | Standard Deviation 0.2899 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+CD16+; Change at Week 12 | -0.2424 percentage of CD45+ cells | Standard Deviation 0.27183 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+CD16+; Change at Week 48 | 0.0250 percentage of CD45+ cells | Standard Deviation 0.37069 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+CD16-; Baseline | 4.3404 percentage of CD45+ cells | Standard Deviation 1.60025 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+CD16-; Change at Week 4 | -1.6758 percentage of CD45+ cells | Standard Deviation 1.55056 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+CD16-; Change at Week 12 | -1.1205 percentage of CD45+ cells | Standard Deviation 2.29278 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+CD16-; Change at Week 48 | -0.7592 percentage of CD45+ cells | Standard Deviation 2.10992 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CD11b+; Baseline | 4.5567 percentage of CD45+ cells | Standard Deviation 1.62497 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CD11b+; Change at Week 4 | -1.6504 percentage of CD45+ cells | Standard Deviation 1.56493 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CD11b+; Change at Week 12 | -1.1155 percentage of CD45+ cells | Standard Deviation 2.31024 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CD11b+; Change at Week 48 | -0.5925 percentage of CD45+ cells | Standard Deviation 2.11151 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CD163+; Baseline | 4.4613 percentage of CD45+ cells | Standard Deviation 1.59602 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CD163+; Change at Week 4 | -1.6679 percentage of CD45+ cells | Standard Deviation 1.64311 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CD163+; Change at Week 12 | -1.1223 percentage of CD45+ cells | Standard Deviation 2.36705 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CD163+; Change at Week 48 | -0.5167 percentage of CD45+ cells | Standard Deviation 2.18389 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CX3CR1+; Baseline | 4.3533 percentage of CD45+ cells | Standard Deviation 1.54303 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CX3CR1+; Change at Week 4 | -1.5529 percentage of CD45+ cells | Standard Deviation 1.41647 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CX3CR1+; Change at Week 12 | -1.2809 percentage of CD45+ cells | Standard Deviation 2.22435 |
| Albutein 5% | Change From Baseline in Immune Population Profile | Monocyte panel: CD14+HLA-DR+ CX3CR1+; Change at Week 48 | -0.5992 percentage of CD45+ cells | Standard Deviation 2.04927 |
Secondary
Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels
Plasma BMAA levels at baseline and over the course of treatment at each evaluation visit were measured to identify reductions in BMAA levels, which could potentially be correlated with disease progression or a halt in disease progression. Analysis was performed using a Thermo TSQ Quantiva triple-stage quadrupole mass spectrometer.
Time frame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses at the given time point.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Albutein 5% | Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels | Baseline | NA ng/mL |
| Albutein 5% | Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels | Change at Week 4 | NA ng/mL |
| Albutein 5% | Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels | Change at Week 12 | NA ng/mL |
| Albutein 5% | Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels | Change at Week 24 | NA ng/mL |
| Albutein 5% | Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels | Change at Week 25 | NA ng/mL |
| Albutein 5% | Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels | Change at Week 48 | NA ng/mL |
Secondary
Change From Baseline in Plasma Cytokine Panel Levels
The plasma cytokine panel includes: transforming growth factor (TGF) beta1, TGF beta2, TGF beta3, interferon (IFN) gamma, interleukins (IL)-1beta, IL-1Ra, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IFN-γ-inducible protein (IP)-10, human monocyte chemoattractant protein (MCP)-1, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1-alpha, MIP-1-beta, tumor necrosis factor (TNF)-alpha, soluble cluster of differentiation (CD) 40 ligand (sCD40L), fractalkine. The level of each of these cytokines are reported as categories. Only categories with values above the level of detection are reported.
Time frame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with detectable values for the analyses of the specific category at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-6; Before PE, Change at Week 48 | 3.3 picogram per milliliter (pg/mL) | Standard Deviation 16.55 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IP-10; Before PE, Change at Week 4 | -38.4 picogram per milliliter (pg/mL) | Standard Deviation 104.78 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IP-10; After PE, Change at Week 12 | -2.7 picogram per milliliter (pg/mL) | Standard Deviation 144.21 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-17A; Before PE, Change at Week 4 | -1.90 picogram per milliliter (pg/mL) | Standard Deviation 1.556 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta1; Baseline | 9998.9 picogram per milliliter (pg/mL) | Standard Deviation 5811.61 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta1; Before PE, Change at Week 4 | -1302.4 picogram per milliliter (pg/mL) | Standard Deviation 7269.45 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta1; After PE, Change at Week 4 | -5922.8 picogram per milliliter (pg/mL) | Standard Deviation 5490.19 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta1; Before PE, Change at Week 12 | 1238.6 picogram per milliliter (pg/mL) | Standard Deviation 7838.89 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta1; After PE, Change at Week 12 | -5476.7 picogram per milliliter (pg/mL) | Standard Deviation 5453.16 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta1; Before PE, Change at Week 24 | -86.6 picogram per milliliter (pg/mL) | Standard Deviation 5270.57 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta1; After PE, Change at Week 24 | -4966.4 picogram per milliliter (pg/mL) | Standard Deviation 4711.24 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta1; Before PE, Change at Week 36 | -1698.5 picogram per milliliter (pg/mL) | Standard Deviation 6124.07 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta1; Before PE, Change at Week 48 | -1160.5 picogram per milliliter (pg/mL) | Standard Deviation 5942.4 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta2; Baseline | 465.8 picogram per milliliter (pg/mL) | Standard Deviation 247.85 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta2; Before PE, Change at Week 4 | -22.1 picogram per milliliter (pg/mL) | Standard Deviation 323.2 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta2; After PE, Change at Week 4 | -244.4 picogram per milliliter (pg/mL) | Standard Deviation 228.25 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta2; Before PE, Change at Week 12 | 64.4 picogram per milliliter (pg/mL) | Standard Deviation 329.48 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta2; After PE, Change at Week 12 | -207.9 picogram per milliliter (pg/mL) | Standard Deviation 203.96 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta2; Before PE, Change at Week 24 | 5.8 picogram per milliliter (pg/mL) | Standard Deviation 259.18 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta2; After PE, Change at Week 24 | -220.4 picogram per milliliter (pg/mL) | Standard Deviation 236.01 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta2; Before PE, Change at Week 36 | -62.5 picogram per milliliter (pg/mL) | Standard Deviation 270.98 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta2; Before PE, Change at Week 48 | -28.1 picogram per milliliter (pg/mL) | Standard Deviation 262.15 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TGF beta3; Baseline | 63.70 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IFN gamma; Baseline | 16.22 picogram per milliliter (pg/mL) | Standard Deviation 9.024 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IFN gamma; Before PE, Change at Week 4 | 8.80 picogram per milliliter (pg/mL) | — |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IFN gamma; Before PE, Change at Week 12 | -5.70 picogram per milliliter (pg/mL) | Standard Deviation 15.415 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IFN gamma; Before PE, Change at Week 24 | -4.70 picogram per milliliter (pg/mL) | Standard Deviation 6.647 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IFN gamma; Before PE, Change at Week 36 | 8.40 picogram per milliliter (pg/mL) | Standard Deviation 3.677 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IFN gamma; Before PE, Change at Week 48 | 9.60 picogram per milliliter (pg/mL) | — |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-17A; After PE, Change at Week 4 | 2.48 picogram per milliliter (pg/mL) | Standard Deviation 1.132 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-17A; Before PE, Change at Week 12 | 1.90 picogram per milliliter (pg/mL) | — |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-17A; After PE, Change at Week 12 | 2.35 picogram per milliliter (pg/mL) | Standard Deviation 0.636 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-17A; Before PE, Change at Week 24 | -0.40 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Interleukin (IL)-1beta; Baseline | 16.10 picogram per milliliter (pg/mL) | — |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-1Ra; Baseline | 56.7 picogram per milliliter (pg/mL) | Standard Deviation 44.19 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-1Ra; Before PE, Change at Week 4 | -7.4 picogram per milliliter (pg/mL) | Standard Deviation 33.93 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-1Ra; After PE, Change at Week 4 | -17.5 picogram per milliliter (pg/mL) | Standard Deviation 17.7 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-1Ra; Before PE, Change at Week 12 | 1.1 picogram per milliliter (pg/mL) | Standard Deviation 31.99 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-1Ra; After PE, Change at Week 12 | -5.7 picogram per milliliter (pg/mL) | Standard Deviation 24.09 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-1Ra; Before PE, Change at Week 24 | 3.3 picogram per milliliter (pg/mL) | Standard Deviation 13.36 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-1Ra; After PE, Change at Week 24 | 1.2 picogram per milliliter (pg/mL) | Standard Deviation 13.79 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-1Ra; Before PE, Change at Week 36 | 0.5 picogram per milliliter (pg/mL) | Standard Deviation 10.31 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-1Ra; Before PE, Change at Week 48 | 3.6 picogram per milliliter (pg/mL) | Standard Deviation 8.79 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-6; Baseline | 160.7 picogram per milliliter (pg/mL) | Standard Deviation 132.82 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-6; Before PE, Change at Week 4 | -0.9 picogram per milliliter (pg/mL) | Standard Deviation 128.32 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-6; After PE, Change at Week 4 | -112.3 picogram per milliliter (pg/mL) | Standard Deviation 64.94 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-17A; After PE, Change at Week 24 | 1.33 picogram per milliliter (pg/mL) | Standard Deviation 1.617 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-17A; Before PE, Change at Week 36 | 1.30 picogram per milliliter (pg/mL) | Standard Deviation 0.283 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-17A; Before PE, Change at Week 48 | 3.00 picogram per milliliter (pg/mL) | — |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IP-10; Baseline | 407.0 picogram per milliliter (pg/mL) | Standard Deviation 133.95 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IP-10; After PE, Change at Week 4 | 27.9 picogram per milliliter (pg/mL) | Standard Deviation 153.91 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IP-10; Before PE, Change at Week 12 | -7.7 picogram per milliliter (pg/mL) | Standard Deviation 122.81 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IP-10; Before PE, Change at Week 24 | -2.1 picogram per milliliter (pg/mL) | Standard Deviation 152.6 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IP-10; After PE, Change at Week 24 | -42.7 picogram per milliliter (pg/mL) | Standard Deviation 166.87 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IP-10; Before PE, Change at Week 36 | 25.6 picogram per milliliter (pg/mL) | Standard Deviation 129.09 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IP-10; Before PE, Change at Week 48 | -23.8 picogram per milliliter (pg/mL) | Standard Deviation 156.5 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Human Monocyte Chemoattractant Protein-1 (MCP-1); Baseline | 239.1 picogram per milliliter (pg/mL) | Standard Deviation 69.94 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MCP-1; Before PE, Change at Week 4 | 44.5 picogram per milliliter (pg/mL) | Standard Deviation 81.02 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MCP-1; After PE, Change at Week 4 | 102.2 picogram per milliliter (pg/mL) | Standard Deviation 117.01 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MCP-1; Before PE, Change at Week 12 | 51.6 picogram per milliliter (pg/mL) | Standard Deviation 118.85 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MCP-1; After PE, Change at Week 12 | 73.7 picogram per milliliter (pg/mL) | Standard Deviation 113.07 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MCP-1; Before PE, Change at Week 24 | 63.2 picogram per milliliter (pg/mL) | Standard Deviation 130.31 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MCP-1; After PE, Change at Week 24 | 40.1 picogram per milliliter (pg/mL) | Standard Deviation 33.36 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-6; Before PE, Change at Week 12 | 6.5 picogram per milliliter (pg/mL) | Standard Deviation 121.65 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-6; After PE, Change at Week 12 | -78.7 picogram per milliliter (pg/mL) | Standard Deviation 130.04 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-6; Before PE, Change at Week 24 | -43.0 picogram per milliliter (pg/mL) | Standard Deviation 23.26 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-6; After PE, Change at Week 24 | -166.9 picogram per milliliter (pg/mL) | — |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-6; Before PE, Change at Week 36 | -18.8 picogram per milliliter (pg/mL) | Standard Deviation 39.89 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MCP-1; Before PE, Change at Week 36 | -41.3 picogram per milliliter (pg/mL) | Standard Deviation 64.66 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MCP-1; Before PE, Change at Week 48 | -25.8 picogram per milliliter (pg/mL) | Standard Deviation 37.85 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Macrophage-Derived Chemokine (MDC); Baseline | 547.7 picogram per milliliter (pg/mL) | Standard Deviation 178.98 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MDC; Before PE, Change at Week 4 | 57.6 picogram per milliliter (pg/mL) | Standard Deviation 135.92 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MDC; After PE, Change at Week 4 | 20.7 picogram per milliliter (pg/mL) | Standard Deviation 220.9 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MDC; Before PE, Change at Week 12 | 41.8 picogram per milliliter (pg/mL) | Standard Deviation 133.82 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-8; Baseline | 48.4 picogram per milliliter (pg/mL) | Standard Deviation 57.66 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-8; Before PE, Change at Week 4 | -4.2 picogram per milliliter (pg/mL) | Standard Deviation 32.27 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-8; After PE, Change at Week 4 | -45.5 picogram per milliliter (pg/mL) | Standard Deviation 24.99 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MDC; After PE, Change at Week 12 | -4.2 picogram per milliliter (pg/mL) | Standard Deviation 164.87 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-8; Before PE, Change at Week 12 | 3.9 picogram per milliliter (pg/mL) | Standard Deviation 39.3 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MDC; Before PE, Change at Week 24 | 98.5 picogram per milliliter (pg/mL) | Standard Deviation 134.08 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MDC; After PE, Change at Week 24 | -73.1 picogram per milliliter (pg/mL) | Standard Deviation 182.85 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MDC; Before PE, Change at Week 36 | 41.4 picogram per milliliter (pg/mL) | Standard Deviation 139.68 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MDC; Before PE, Change at Week 48 | -16.3 picogram per milliliter (pg/mL) | Standard Deviation 121.81 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Macrophage Inflammatory Protein (MIP-1) alpha; Baseline | 7.54 picogram per milliliter (pg/mL) | Standard Deviation 4.109 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 alpha; Before PE, Change at Week 4 | -0.43 picogram per milliliter (pg/mL) | Standard Deviation 4.971 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-8; After PE, Change at Week 12 | -38.4 picogram per milliliter (pg/mL) | Standard Deviation 9.98 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-8; Before PE, Change at Week 24 | -9.3 picogram per milliliter (pg/mL) | Standard Deviation 7.64 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-8; After PE, Change at Week 24 | -24.8 picogram per milliliter (pg/mL) | Standard Deviation 35 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-8; Before PE, Change at Week 36 | -8.3 picogram per milliliter (pg/mL) | Standard Deviation 10.1 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-8; Before PE, Change at Week 48 | -1.2 picogram per milliliter (pg/mL) | Standard Deviation 4.41 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-10; Baseline | 10.34 picogram per milliliter (pg/mL) | Standard Deviation 13.056 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-10; Before PE, Change at Week 4 | -4.70 picogram per milliliter (pg/mL) | Standard Deviation 9.731 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-10; After PE, Change at Week 4 | -4.46 picogram per milliliter (pg/mL) | Standard Deviation 12.398 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-10; Before PE, Change at Week 12 | -0.25 picogram per milliliter (pg/mL) | Standard Deviation 2.638 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-10; After PE, Change at Week 12 | -0.45 picogram per milliliter (pg/mL) | Standard Deviation 2.626 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-10; Before PE, Change at Week 24 | -0.50 picogram per milliliter (pg/mL) | Standard Deviation 1.354 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-10; After PE, Change at Week 24 | -1.13 picogram per milliliter (pg/mL) | Standard Deviation 1.181 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-10; Before PE, Change at Week 36 | 1.38 picogram per milliliter (pg/mL) | Standard Deviation 2.72 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 alpha; After PE, Change at Week 4 | -2.50 picogram per milliliter (pg/mL) | Standard Deviation 4.59 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 alpha; Before PE, Change at Week 12 | 0.46 picogram per milliliter (pg/mL) | Standard Deviation 3.58 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 alpha; After PE, Change at Week 12 | -1.10 picogram per milliliter (pg/mL) | Standard Deviation 2.691 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 alpha; Before PE, Change at Week 24 | -0.80 picogram per milliliter (pg/mL) | Standard Deviation 0.283 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 alpha; After PE, Change at Week 24 | -1.50 picogram per milliliter (pg/mL) | — |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 alpha; Before PE, Change at Week 36 | 0.63 picogram per milliliter (pg/mL) | Standard Deviation 0.351 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 alpha; Before PE, Change at Week 48 | 1.05 picogram per milliliter (pg/mL) | Standard Deviation 0.636 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 beta; Baseline | 60.33 picogram per milliliter (pg/mL) | Standard Deviation 24.913 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 beta; Before PE, Change at Week 4 | -1.17 picogram per milliliter (pg/mL) | Standard Deviation 18.954 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 beta; After PE, Change at Week 4 | 3.97 picogram per milliliter (pg/mL) | Standard Deviation 33.788 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 beta; Before PE, Change at Week 12 | -1.48 picogram per milliliter (pg/mL) | Standard Deviation 15.869 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 beta; After PE, Change at Week 12 | 3.33 picogram per milliliter (pg/mL) | Standard Deviation 31.079 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 beta; Before PE, Change at Week 24 | -3.97 picogram per milliliter (pg/mL) | Standard Deviation 13.444 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 beta; After PE, Change at Week 24 | -8.61 picogram per milliliter (pg/mL) | Standard Deviation 17.402 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 beta; Before PE, Change at Week 36 | 0.33 picogram per milliliter (pg/mL) | Standard Deviation 16.394 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | MIP-1 beta; Before PE, Change at Week 48 | -6.58 picogram per milliliter (pg/mL) | Standard Deviation 12.213 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Tumor Necrosis Factor-Alpha (TNF alpha); Baseline | 16.80 picogram per milliliter (pg/mL) | Standard Deviation 4.832 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TNF alpha; Before PE, Change at Week 4 | -1.38 picogram per milliliter (pg/mL) | Standard Deviation 5.803 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TNF alpha; After PE, Change at Week 4 | 1.11 picogram per milliliter (pg/mL) | Standard Deviation 5.766 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TNF alpha; Before PE, Change at Week 12 | -0.06 picogram per milliliter (pg/mL) | Standard Deviation 6.45 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TNF alpha; After PE, Change at Week 12 | -0.07 picogram per milliliter (pg/mL) | Standard Deviation 3.645 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TNF alpha; Before PE, Change at Week 24 | -2.77 picogram per milliliter (pg/mL) | Standard Deviation 2.229 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-10; Before PE, Change at Week 48 | 2.50 picogram per milliliter (pg/mL) | Standard Deviation 0.707 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-12 p70; Baseline | 11.95 picogram per milliliter (pg/mL) | Standard Deviation 2.026 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TNF alpha; After PE, Change at Week 24 | 0.03 picogram per milliliter (pg/mL) | Standard Deviation 3.673 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TNF alpha; Before PE, Change at Week 36 | -0.74 picogram per milliliter (pg/mL) | Standard Deviation 3.97 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | TNF alpha; Before PE, Change at Week 48 | -2.37 picogram per milliliter (pg/mL) | Standard Deviation 4.474 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | sCD40L; Baseline | 137.3 picogram per milliliter (pg/mL) | Standard Deviation 83.74 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | sCD40L; Before PE, Change at Week 4 | 31.6 picogram per milliliter (pg/mL) | Standard Deviation 160.97 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-12 p70; Before PE, Change at Week 12 | 2.10 picogram per milliliter (pg/mL) | — |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-12 p70; Before PE, Change at Week 24 | -1.25 picogram per milliliter (pg/mL) | Standard Deviation 3.041 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | sCD40L; After PE, Change at Week 4 | -52.3 picogram per milliliter (pg/mL) | Standard Deviation 81.2 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-12 p70; After PE, Change at Week 24 | -2.15 picogram per milliliter (pg/mL) | Standard Deviation 1.768 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | sCD40L; Before PE, Change at Week 12 | 48.9 picogram per milliliter (pg/mL) | Standard Deviation 138.73 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-12 p70; Before PE, Change at Week 36 | 0.90 picogram per milliliter (pg/mL) | Standard Deviation 1.273 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | sCD40L; After PE, Change at Week 12 | -31.2 picogram per milliliter (pg/mL) | Standard Deviation 91.56 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | sCD40L; Before PE, Change at Week 24 | 47.8 picogram per milliliter (pg/mL) | Standard Deviation 188.88 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | sCD40L; After PE, Change at Week 24 | -49.8 picogram per milliliter (pg/mL) | Standard Deviation 56.5 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | sCD40L; Before PE, Change at Week 36 | -2.4 picogram per milliliter (pg/mL) | Standard Deviation 39.84 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | sCD40L; Before PE, Change at Week 48 | -30.1 picogram per milliliter (pg/mL) | Standard Deviation 93.64 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Fractalkine; Baseline | 240.6 picogram per milliliter (pg/mL) | Standard Deviation 69.12 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Fractalkine; Before PE, Change at Week 4 | -63.6 picogram per milliliter (pg/mL) | Standard Deviation 111.89 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Fractalkine; After PE, Change at Week 4 | -32.1 picogram per milliliter (pg/mL) | Standard Deviation 73.32 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Fractalkine; Before PE, Change at Week 12 | 2.0 picogram per milliliter (pg/mL) | Standard Deviation 103.06 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Fractalkine; After PE, Change at Week 12 | -35.0 picogram per milliliter (pg/mL) | — |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Fractalkine; Before PE, Change at Week 24 | -10.5 picogram per milliliter (pg/mL) | Standard Deviation 34.89 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Fractalkine; After PE, Change at Week 24 | -43.3 picogram per milliliter (pg/mL) | Standard Deviation 5.59 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Fractalkine; Before PE, Change at Week 36 | -5.7 picogram per milliliter (pg/mL) | Standard Deviation 81.28 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | Fractalkine; Before PE, Change at Week 48 | 15.0 picogram per milliliter (pg/mL) | Standard Deviation 104.63 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-12 p70; Before PE, Change at Week 48 | 2.15 picogram per milliliter (pg/mL) | Standard Deviation 4.313 |
| Albutein 5% | Change From Baseline in Plasma Cytokine Panel Levels | IL-17A; Baseline | 5.28 picogram per milliliter (pg/mL) | Standard Deviation 4.351 |
Secondary
Change From Baseline in Plasma Human Apolipoprotein Levels
The levels of human Apolipoprotein (ApoE) in plasma were measured by enzyme-linked immunosorbent assay (ELISA).
Time frame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Plasma Human Apolipoprotein Levels | Baseline | 6753.8 nanogram per milliliter (ng/mL) | Standard Deviation 3549.07 |
| Albutein 5% | Change From Baseline in Plasma Human Apolipoprotein Levels | Before PE, Change at Week 4 | 645.9 nanogram per milliliter (ng/mL) | Standard Deviation 2122 |
| Albutein 5% | Change From Baseline in Plasma Human Apolipoprotein Levels | After PE, Change at Week 4 | -3978.2 nanogram per milliliter (ng/mL) | Standard Deviation 2749.25 |
| Albutein 5% | Change From Baseline in Plasma Human Apolipoprotein Levels | Before PE, Change at Week 12 | 611.5 nanogram per milliliter (ng/mL) | Standard Deviation 3014.69 |
| Albutein 5% | Change From Baseline in Plasma Human Apolipoprotein Levels | After PE, Change at Week 12 | -3504.2 nanogram per milliliter (ng/mL) | Standard Deviation 3434.69 |
| Albutein 5% | Change From Baseline in Plasma Human Apolipoprotein Levels | Before PE, Change at Week 24 | -555.3 nanogram per milliliter (ng/mL) | Standard Deviation 2782.05 |
| Albutein 5% | Change From Baseline in Plasma Human Apolipoprotein Levels | After PE, Change at Week 24 | -4711.3 nanogram per milliliter (ng/mL) | Standard Deviation 3142.53 |
| Albutein 5% | Change From Baseline in Plasma Human Apolipoprotein Levels | Before PE, Change at Week 36 | 643.0 nanogram per milliliter (ng/mL) | Standard Deviation 2306.95 |
| Albutein 5% | Change From Baseline in Plasma Human Apolipoprotein Levels | Before PE, Change at Week 48 | 861.0 nanogram per milliliter (ng/mL) | Standard Deviation 4242.19 |
Secondary
Change From Baseline in Plasma Neurofilament Levels
Levels of neurofilaments: Phosphorylated Neurofilament heavy chain (pNF-H) and Neurofilament light chain (NF-L) were measured by Enzyme-Linked Immunosorbent Assay (ELISA).
Time frame: Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses of the specific category at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | pNF-heavy, Baseline | 7.26 ng/mL | Standard Deviation 5.811 |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | pNF-heavy, Before PE Change at Week 4 | -1.29 ng/mL | Standard Deviation 4.362 |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | pNF-heavy, After PE Change at Week 4 | -5.46 ng/mL | Standard Deviation 4.792 |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | pNF-heavy, Before PE Change at Week 12 | -0.99 ng/mL | Standard Deviation 4.709 |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | pNF-heavy, After PE Change at Week 12 | -4.97 ng/mL | Standard Deviation 4 |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | pNF-heavy, Before PE Change at Week 24 | -0.93 ng/mL | Standard Deviation 0.883 |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | pNF-heavy, After PE Change at Week 24 | -3.39 ng/mL | Standard Deviation 2.265 |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | pNF-heavy, Before PE Change at Week 36 | 0.47 ng/mL | Standard Deviation 3.526 |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | pNF-heavy, Before PE Change at Week 48 | 1.50 ng/mL | Standard Deviation 2.471 |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | NF-light, Baseline | NA ng/mL | — |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | NF-light, Before PE Change at Week 4 | NA ng/mL | — |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | NF-light, After PE Change at Week 4 | NA ng/mL | — |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | NF-light, Before PE Change at Week 12 | NA ng/mL | — |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | NF-light, After PE Change at Week 12 | NA ng/mL | — |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | NF-light, Before PE Change at Week 24 | NA ng/mL | — |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | NF-light, After PE Change at Week 24 | NA ng/mL | — |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | NF-light, Before PE Change at Week 36 | NA ng/mL | — |
| Albutein 5% | Change From Baseline in Plasma Neurofilament Levels | NF-light, Before PE Change at Week 48 | NA ng/mL | — |
Secondary
Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG)
Surface EMG was performed to record motor evoked potential in the distal muscles of the upper limbs (thenar and hypothenar eminence) and dorsiflexor muscles of the lower limbs (anterior tibialis) after electrical stimulation on the median, ulnar, and external popliteal sciatic nerve. The data for motor evoked potential (in millivolt \[mv\]) is reported for thenar muscles of both upper limbs and hypothenar muscle of the upper right limb and anterior tibialis of the both lower limbs.
Time frame: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and a measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for the specific category at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Thenar Eminence, Change at Week 36 | -1.4 millivolt (mV) | Standard Deviation 2.48 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Tibialis Anterior, Baseline | 4.1 millivolt (mV) | Standard Deviation 2.36 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Tibialis Anterior, Change at Week 4 | -0.4 millivolt (mV) | Standard Deviation 1.49 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Tibialis Anterior, Change at Week 12 | -0.1 millivolt (mV) | Standard Deviation 1.85 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Tibialis Anterior, Change at Week 25 | -1.3 millivolt (mV) | Standard Deviation 3.19 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Tibialis Anterior, Change at Week 36 | -0.7 millivolt (mV) | Standard Deviation 3.72 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Tibialis Anterior, Change at Week 48 | -1.6 millivolt (mV) | Standard Deviation 3.46 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Tibialis Anterior, Baseline | 4.2 millivolt (mV) | Standard Deviation 2.02 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Tibialis Anterior, Change at Week 4 | -0.7 millivolt (mV) | Standard Deviation 1.72 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Tibialis Anterior, Change at Week 12 | -0.6 millivolt (mV) | Standard Deviation 2.13 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Tibialis Anterior, Change at Week 25 | -0.7 millivolt (mV) | Standard Deviation 2.69 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Tibialis Anterior, Change at Week 36 | -0.8 millivolt (mV) | Standard Deviation 3.58 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Tibialis Anterior, Change at Week 48 | -1.3 millivolt (mV) | Standard Deviation 3.36 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Thenar Eminence, Baseline | 4.3 millivolt (mV) | Standard Deviation 3.01 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Thenar Eminence, Change at Week4 | -0.3 millivolt (mV) | Standard Deviation 1.18 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Thenar Eminence, Change at Week 12 | -0.6 millivolt (mV) | Standard Deviation 1.29 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Thenar Eminence, Change at Week 25 | -1.3 millivolt (mV) | Standard Deviation 2.39 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Thenar Eminence, Change at Week 36 | -1.5 millivolt (mV) | Standard Deviation 2.4 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Thenar Eminence, Change at Week 48 | -2.1 millivolt (mV) | Standard Deviation 2.78 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Thenar Eminence, Baseline | 3.8 millivolt (mV) | Standard Deviation 3.2 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Thenar Eminence, Change at Week 4 | 0.2 millivolt (mV) | Standard Deviation 1.63 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Thenar Eminence, Change at Week 12 | -0.2 millivolt (mV) | Standard Deviation 1.34 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Thenar Eminence, Change at Week 25 | 0.3 millivolt (mV) | Standard Deviation 2.61 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Left Thenar Eminence, Change at Week 48 | -0.9 millivolt (mV) | Standard Deviation 1.83 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Hypothenar Eminence, Baseline | 6.4 millivolt (mV) | Standard Deviation 2.5 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Hypothenar Eminence, Change at Week 4 | -0.5 millivolt (mV) | Standard Deviation 1.23 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Hypothenar Eminence, Change at Week 12 | -1.1 millivolt (mV) | Standard Deviation 0.82 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Hypothenar Eminence, Change at Week 25 | -1.9 millivolt (mV) | Standard Deviation 2.24 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Hypothenar Eminence, Change at Week 36 | -2.6 millivolt (mV) | Standard Deviation 2.29 |
| Albutein 5% | Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG) | Right Hypothenar Eminence, Change at Week 48 | -3.2 millivolt (mV) | Standard Deviation 1.41 |
Secondary
Change From Cerebrospinal Fluid (CSF) Beta-methylamino-L-alanine (BMAA) Levels
CSF BMAA levels at baseline and over the course of treatment at each evaluation visit were measured to identify reductions in BMAA levels, which could potentially be correlated with disease progression or a halt in disease progression. Analysis was performed using a Thermo TSQ Quantiva triple quadrupole mass spectrometer.
Time frame: Baseline (Week 0), Weeks 12, and 25
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for analyses at the given time point.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Albutein 5% | Change From Cerebrospinal Fluid (CSF) Beta-methylamino-L-alanine (BMAA) Levels | Change at Week 12 | NA ng/mL |
| Albutein 5% | Change From Cerebrospinal Fluid (CSF) Beta-methylamino-L-alanine (BMAA) Levels | Baseline | NA ng/mL |
| Albutein 5% | Change From Cerebrospinal Fluid (CSF) Beta-methylamino-L-alanine (BMAA) Levels | Change at Week 25 | NA ng/mL |
Secondary
Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score
The ALS questionnaire consists of 40 items grouped into 5 representative dimensions associated with quality of life. The first four dimensions were: physical mobility (questions 1-10), activities of daily living (questions 11- 20), food and drink (questions 21-23), communication (questions 24-30) and emotional function (questions 31-40), refer to deficits and subsequent disabilities as a result of the disease. The fifth scale (emotional functioning) reflects how the participant is facing his/her physical deterioration emotionally. Each item is scored from 0 to 4 according to a gradation of symptom onset frequency (never, rarely, sometimes, often, always). From raw scores, an index from 0 to 100 is obtained for each dimension, which make comparisons with the other dimensions possible as well as a straightforward interpretation of the results (0 = better state of health as measured by the questionnaire;100 = poorer state of health). A negative change from Baseline indicates improvement.
Time frame: Weeks 25 and 48
Population: Evaluable Population included all participants who received at least one PE treatment with albutein 5% and also had at least one baseline determination and a measurement of a primary efficacy variable at a subsequent visit. Number analyzed is the number of participants with data available for the specific category at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | Communication Week 48 | 9.7 units on a scale | Standard Deviation 12.49 |
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | Physical mobility Week 25 | 23.6 units on a scale | Standard Deviation 17.61 |
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | Physical mobility Week 48 | 20.7 units on a scale | Standard Deviation 15.26 |
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | ADL/independence Week 25 | 25.4 units on a scale | Standard Deviation 15.91 |
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | ADL/independence Week 48 | 27.9 units on a scale | Standard Deviation 14.82 |
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | Eating and drinking Week 25 | 8.3 units on a scale | Standard Deviation 21.52 |
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | Eating and drinking Week 48 | 14.3 units on a scale | Standard Deviation 29.94 |
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | Communication Week 25 | 7.7 units on a scale | Standard Deviation 11.92 |
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | Emotional functioning Week 25 | 8.9 units on a scale | Standard Deviation 14.5 |
| Albutein 5% | Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score | Emotional functioning Week 48 | 11.4 units on a scale | Standard Deviation 17.13 |
Other Pre-specified
Incidence of All AEs
Time frame: Weeks -2 to 48
Other Pre-specified
Percentage of PE Sessions Associated With at Least One Adverse Event (AE), Irrespective of Causality
Time frame: During or within 72 hours after the completion of the product infusion
Other Pre-specified
Percentage of PE Sessions Associated With at Least One Adverse Reaction (AR)
Time frame: During or within 72 hours after the completion of the product infusion