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| Name | Class |
|---|---|
| Grifols Biologicals, LLC | INDUSTRY |
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The purpose of this study was to evaluate the efficacy and safety of plasma exchange with 5% albumin in beta-amyloid peptide clearance in cerebrospinal fluid, and its effects in patients with mild-moderate Alzheimer's disease.
A phase II study was conducted primarily to determine whether plasma exchange with 5% human albumin is able to modify the concentration of beta-amyloid peptide in cerebrospinal fluid (CSF) in patients with AD.
After screening and randomization, treatment proceeded as follows:
The control group followed the same program, except for the plasma exchanges. After the treatment period ended, subjects followed-up for a 6-month period of time.
The trial comprises a global multicenter (Spain and US), blind, randomized, controlled design. The trials key coordination is based in Spain where Dr. Boada (see Study Officials/Investigators) is the main study official.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Albutein 5% | Experimental | Patients allocated to this arm underwent plasma exchange with Albutein 5%. |
|
| Control | Sham Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Albutein 5% | Biological | 18 Plasma Exchanges using Albutein 5%:
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels. | Change in levels of Aβ1-42 in CSF in the period between baseline lumbar puncture (before the start of treatment) and lumbar puncture immediately after the end of the last plasma exchange (whenever this may be). Separate assays of Aβ1-42 were performed with Innotest and The Genetics Company commercial kits. | Baseline and up to week 44 |
| Measure | Description | Time Frame |
|---|---|---|
| P-Tau and Tau CSF Levels Throughout the Study. | Levels of Tau and P-tau in CSF throughout the treatment phase and the follow-up phase (week 44). | Baseline, week 02, week 08, week 20, week 33 and week 44 |
| Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Merce Boada, MD | Fundació ACE | Principal Investigator |
| Laura Núñez | Grifols Biologicals, LLC | Study Director |
| Antonio Paez | Grifols Biologicals, LLC | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Howard University | Washington D.C. | District of Columbia | 20059 | United States | ||
| Mid-Atlantic Geriatric/ARC |
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| ID | Title | Description |
|---|---|---|
| FG000 | Albutein 5% | 18 Plasma Exchanges using Albutein 5%:
|
| FG001 | Control (Sham Procedure) | Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Randomized |
|
| |||||||||||||||||||||
| Intensive Period |
| ||||||||||||||||||||||
| Maintenance I |
| ||||||||||||||||||||||
| Maintenance II |
|
The baseline analysis population included all randomized subjects who received at least one plasma exchange session or one sham procedure.
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| ID | Title | Description |
|---|---|---|
| BG000 | Albutein 5% | 18 Plasma Exchanges using Albutein 5%:
|
| BG001 | Control |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Aβ1-42 Cerebrospinal Fluid (CSF) Levels. | Change in levels of Aβ1-42 in CSF in the period between baseline lumbar puncture (before the start of treatment) and lumbar puncture immediately after the end of the last plasma exchange (whenever this may be). Separate assays of Aβ1-42 were performed with Innotest and The Genetics Company commercial kits. | The efficacy analyses were performed with the full analysis set (FAS) population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions (or sham procedures) during the intensive treatment phase (the three first weeks of treatment). | Posted | Least Squares Mean | 95% Confidence Interval | pg/mL | Baseline and up to week 44 |
|
Primary criterion of safety was % of plasma exchange (PE) associated with at least one adverse event (AE) that may be related to the study procedure (adverse reaction).
In addition, global consideration will be made of the percentage PE involving some AE, whether or not related to the procedure. Vital signs, anxiety and restlessness tests and the criterion of the investigator were also used to evaluate patient safety.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Albutein 5% | 18 Plasma Exchanges using Albutein 5%:
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Medical device complication | General disorders | MedDRA 13.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mireia Torres | Instituto Grifols S.A. | +34935710500 | 12273 | mireia.torres@grifols.com |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D003704 | Dementia |
| D058225 | Plaque, Amyloid |
| D002493 | Central Nervous System Diseases |
| D001927 | Brain Diseases |
| D001523 | Mental Disorders |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
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|
| Control | Other | Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements) |
|
Plasma levels of Aβ1-40 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using The Genetics Company commercial kits). |
| Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44. |
| Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Plasma levels of Aβ1-42 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using The Genetics Company commercial kits). | Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44 |
| Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Plasma levels of Aβ1-42 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using Innotest commercial kits). | Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44. |
| Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | Change in the cognitive, functional and neuropsychiatric scores and overall development.
| Change from baseline at week 44 |
| Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | Change in the cognitive, functional and neuropsychiatric scores and overall development.
| Change from baseline at week 44 |
| Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Structural changes in volume of the hippocampus, posterior cingular area, and other associated areas by Magnetic Resonance Imaging (MRI). Three measurements were made (week -2 or -1, 20 and 44). It was measured the variations versus the baseline. | Week 00 (baseline), week 20 and week 44 |
| Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT) | Percentage of patients with improved perfusion at the end of the study compared to their initial perfusion. Frontal, parietal and temporal lobes were evaluated from the quantified NeuroGam images. This rendered parametric images showed brain alterations with more than 2 standard deviations with respect to a normal data base. Initial parametric images were compared to the final ones and it was considered perfusion improvement those patients that showed less stretch and/or defect intensity. | End of study |
| Whiting |
| New Jersey |
| 08759 |
| United States |
| Fundació ACE | Barcelona | Catalonia | 08028 | Spain |
| Hospital General Universitario Gregorio Marañon | Madrid | Madrid | 28007 | Spain |
| Physician Decision |
|
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
| NOT COMPLETED |
|
Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements) |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | Kg |
|
| Height | Mean | Standard Deviation | cm |
|
| OG001 | Control (Sham Procedure) | Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements) |
|
|
| Secondary | P-Tau and Tau CSF Levels Throughout the Study. | Levels of Tau and P-tau in CSF throughout the treatment phase and the follow-up phase (week 44). | The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment). | Posted | Mean | Standard Deviation | pg/mL | Baseline, week 02, week 08, week 20, week 33 and week 44 |
|
|
|
| Secondary | Aβ1-40 Plasma Levels Before and After Each Study Period (The Genetics Company). | Plasma levels of Aβ1-40 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using The Genetics Company commercial kits). | The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment). | Posted | Mean | Standard Deviation | pg/mL | Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44. |
|
|
|
| Secondary | Aβ1-42 Plasma Levels Before and After Each Study Period (The Genetics Company). | Plasma levels of Aβ1-42 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using The Genetics Company commercial kits). | The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment). | Posted | Mean | Standard Deviation | pg/mL | Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44 |
|
|
|
| Secondary | Aβ1-42 Plasma Levels Before and After Each Study Period (Innotest). | Plasma levels of Aβ1-42 before and after the Intensive period, Maintenance period I, Maintenance period II and the Follow-up phase (using Innotest commercial kits). | The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment). | Posted | Mean | Standard Deviation | pg/mL | Baseline, pre-plasma exchange 1 (PRE-PE1), post-plasma exchange 6 (POST-PE6), pre-plasma exchange 7 (PRE-PE7), post-plasma exchange 12 (POST-PE12), pre-plasma exchange 13 (PRE-PE13), post-plasma exchange 18 (POST-PE18), week 33 and week 44. |
|
|
|
| Secondary | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (MMSE, ADAS-Cog, NPS Battery and CSDD) | Change in the cognitive, functional and neuropsychiatric scores and overall development.
| The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment). | Posted | Mean | Standard Deviation | units on a scale | Change from baseline at week 44 |
|
|
|
| Secondary | Change From Baseline to Week 44 in Cognitive, Functional and Neuropsychiatric Scores (ADCS-ADL, NPI, CDR-Sb and ADCS-CGIC). | Change in the cognitive, functional and neuropsychiatric scores and overall development.
| The efficacy analyses were performed with the FAS population which was defined as the set of subjects who were randomized, and received at least three plasma exchange sessions during the intensive treatment phase (the three first weeks of treatment). | Posted | Mean | Standard Deviation | units on a scale | Change from baseline at week 44 |
|
|
|
| Secondary | Magnetic Resonance Imaging (MRI) Structural Changes Variations Versus Baseline. | Structural changes in volume of the hippocampus, posterior cingular area, and other associated areas by Magnetic Resonance Imaging (MRI). Three measurements were made (week -2 or -1, 20 and 44). It was measured the variations versus the baseline. | We analyzed two groups of patients, a treatment group of 20 patients, and a control group, also of 20 patients | Posted | Mean | Standard Deviation | cubic centimetres (cc) | Week 00 (baseline), week 20 and week 44 |
|
|
|
| Secondary | Variations in Hypoperfusion Based on Single Photon Emission Computed Tomography (SPECT) | Percentage of patients with improved perfusion at the end of the study compared to their initial perfusion. Frontal, parietal and temporal lobes were evaluated from the quantified NeuroGam images. This rendered parametric images showed brain alterations with more than 2 standard deviations with respect to a normal data base. Initial parametric images were compared to the final ones and it was considered perfusion improvement those patients that showed less stretch and/or defect intensity. | We analyzed two groups of patients, a treatment group of 20 patients, and a control group, also of 20 patients | Posted | Number | percentage of participants | End of study |
|
|
|
| 3 |
| 19 |
| 18 |
| 19 |
| EG001 | Control (Sham Procedure) | Control group followed the same schedule; however, they did not undergo plasma replacement (it was subjected to simulated plasma replacements) | 2 | 20 | 14 | 20 |
| Cholangitis | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Loss of conscieousness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Partial seizures | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Ocular hypertension | Eye disorders | MedDRA 13.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Catheter site haemorrage | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
|
| Procedural dizziness | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Muscle haemorrage | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Periarthritis | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dementia Alzheimer's type | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Aggression | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Confusion state | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Depressive symptom | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Disinhibition | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Photosensivity reaction | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Bunion operation | Surgical and medical procedures | MedDRA 13.1 | Systematic Assessment |
|
| Urinary cistectomy | Surgical and medical procedures | MedDRA 13.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
Investigators are free to publish the results after signing the final report. When several papers are published, each one will be mainly prepared by the more experienced investigator who will appear as first author. The rest of co-authors will appear in the order considered opportune by the principal investigator. Sponsor will receive a copy of the manuscript for review at least 30 days prior to submission for publication or presentation of the abstract at some scientific meeting.
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| P-Tau (week 08) (n=15; n=18) |
|
| P-Tau (week 20) (n=15; n=18) |
|
| P-Tau (week 33) (n=14; n=15) |
|
| P-Tau (week 44) (n=14; n=14) |
|
| Tau (baseline) (n=18; n=19) |
|
| Tau (week 02) (n=16; n=19) |
|
| Tau (week 08) (n=15; n=18) |
|
| Tau (week 20) (n=15; n=18) |
|
| Tau (week 33) (n=14; n=15) |
|
| Tau (week 44) (n=14; n=14) |
|
| Aβ1-40 POST-PE6 (Intensive) (n=15; n=19) |
|
| Aβ1-40 PRE-PE7(Maintenance I) (n=14; n=17) |
|
| Aβ1-40 POST-PE12 (Maintenance I) (n=14; n=18) |
|
| Aβ1-40 PRE-PE13 (Maintenance II) (n=15; n=19) |
|
| Aβ1-40 POST-PE18 (Maintenance II) (n=14; n=18) |
|
| Follow up (33 week) (n=14; n=15) |
|
| Follow up (44 week) (n=15; n=14) |
|
| Aβ1-42 POST-PE6 (Intensive) (n=15; n=19) |
|
| Aβ1-42 PRE-PE7 (Maintenance) (n=14; n=17) |
|
| Aβ1-42 POST-PE12 (Maintenance I) (n=14; n=18) |
|
| Aβ1-42 PRE-PE13 (Maintenance II) (n=15; n=19) |
|
| Aβ1-42 POST-PE18 (Maintenance II) (n=14; n=18) |
|
| Follow up (44 week) (n=15; n=14) |
|
| Aβ1-42 POST-PE6 (Intensive) (n=15; n=19) |
|
| Aβ1-42 PRE-PE7 (Maintenance I) (n=14; n=17) |
|
| Aβ1-42 POST-PE12 (Maintenance I) (n=14; n=18) |
|
| Aβ1-42 PRE-PE13 (Maintenance II) (n=15; n=19) |
|
| Aβ1-42 POST-PE18 (Maintenance II) (n=14; n=18) |
|
| Follow up (33 week) (n=14; n=15) |
|
| Follow up (44 week) (n=15; n=14) |
|
| NPS (SDMT) (n=15; n=14) |
|
| NPS (SVF) (n=15; n=14) (n=15; n=14) |
|
| NPS (PVF(F)) (n=15; n=14) |
|
| NPS (PVF(A)) (n=15; n=14) |
|
| NPS (PVF(S)) (n=15; n=14) |
|
| NPS (BNT) (n=15; n=14) |
|
| NPS (RAVLT Intermediate 1) (n=15; n=14) |
|
| NPS (RAVLT Intermediate 2) (n=15; n=14) |
|
| NPS (RAVLT Intermediate 3) (n=15; n=14) |
|
| NPS (RAVLT Intermediate 4) (n=15; n=14) |
|
| NPS (RAVLT Intermediate 5) (n=15; n=14) |
|
| NPS (RAVLT Delayed) (n=15; n=14) |
|
| CSDD (patient) (n=10; n=7) |
|
| CSDD (caregiver) (n=13; n=11) |
|
| NPI (total distress) (n=15; n=14) |
|
| CDR Sb score (n=15; n=14) |
|
| ADCS-CGIC (n=15; n=14) |
|
| Hippocampus L (week 44) |
|
| Hippocampus R (week 00) |
|
| Hippocampus R (week 20) |
|
| Hippocampus R (week 44) |
|
| Post Cingulate (week 00) |
|
| Post Cingulate (week 20) |
|
| Post Cingulate (week 44) |
|
| Total Intracranial Volume (week 00) |
|
| Total Intracranial Volume (week 20) |
|
| Total Intracranial Volume (week 44) |
|
| Frontal |
|