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The study participants are patients which have been diagnosed with Guillain-Barré Syndrome (GBS) and are planned to receive treatment with intravenous immunoglobulin (IVIg). IVIg is a standard of care treatment for GBS patients. The patients in this study will be treated with the study medicine imlifidase on day 1, and with IVIg on days 3-7.
The purpose of this study is to investigate the safety and effectiveness of imlifidase in patients diagnosed with GBS.
This is an open-label, single arm, multi-centre, phase II study of imlifidase in combination with standard care IVIg in patients with GBS.
The study will recruit approximately 30 patients who are eligible for IVIg treatment based on current practice (i.e. GBS disability score >3 and within 10 days of onset of weakness). All patients will receive imlifidase (Day 1) prior to standard care IVIg.
There is growing body of evidence suggesting that GBS is an antibody-mediated disorder. In addition to supportive care, IVIg and Plasma Exchange (PE) are the two main immunological treatment options aimed at attenuating the autoreactive humoral immune response. Imlifidase is an IgG degrading enzyme with strict specificity. The hypothesis is that reduction of pathological antibodies may result in aborted progression, quicker recovery and less severe disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Imlifidase | Experimental | One (1) dose of imlifidase, 0.25 mg/kg, will be administered IV over 30 minutes, Day 1. IVIg, 0.4 g/kg, will be administered for 5 consecutive Days, starting on Day 3 at least 48 h after imlifidase administration. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Imlifidase | Drug | All subjects will receive imlifidase (Day 1) prior to standard care IVIg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 1 Grade | Efficacy is assessed as proportion of subjects with improvement of one (1) or more grades in disability outcome on the 6-point GBS DS over time. The 6-point Guillain Barré Syndrome disability score (GBS DS) is a widely accepted and easily obtainable scoring system used to assess disability status of GBS subjects. The DS score is as follows: 0=Healthy, 1=Minor symptoms and capable of running (subjects must be asked to run), 2=Able to walk independently 10 meters or more but unable to run, 3=Able to walk more than 10 meters across an open space with help, 4=Bedridden or chair bound, 5=Needing mechanical ventilation, 6=Dead | Baseline to Day 360 |
| Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 2 Grades | Efficacy is assessed as proportion of subjects with improvement of one (1) or more grades in disability outcome on the 6-point GBS DS over time. The 6-point Guillain Barré Syndrome disability score (GBS DS) is a widely accepted and easily obtainable scoring system used to assess disability status of GBS subjects. The DS score is as follows: 0=Healthy, 1=Minor symptoms and capable of running (subjects must be asked to run), 2=Able to walk independently 10 meters or more but unable to run, 3=Able to walk more than 10 meters across an open space with help, 4=Bedridden or chair bound, 5=Needing mechanical ventilation, 6=Dead | Baseline to Day 360 |
| Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided | Efficacy is assessed as proportion of subjects able to walk unaided (i.e. GBS DS=2) over time | Baseline to Day 360 |
| Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1) | Efficacy is assessed as proportion of patients able to run (i.e. Guillain Barré Syndrome disability score [GBS DS] ≤1) over time | Baseline to Day 360 |
| Measure | Description | Time Frame |
|---|---|---|
| PK Profile of Imlifidase: Cmax | Cmax=Maximum observed plasma concentration of imlifidase following dosing | Within 2 hours before imlifidase dose until Day 15 |
| PK Profile of Imlifidase: Tmax | Tmax=Time point for maximum observed plasma concentration of imlifidase following dosing |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Operations | Hansa Biopharma AB | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Le Kremlin-Bicêtre. Service Neurologie | Le Kremlin-Bicêtre | Paris | 94270 | France | ||
| CHU Bordeaux - Hôpital Pellegrin Tripode |
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| ID | Title | Description |
|---|---|---|
| FG000 | Imlifidase | One (1) dose of imlifidase, 0.25 mg/kg, will be administered IV over 30 minutes, Day 1. IVIg, 0.4 g/kg, will be administered for 5 consecutive Days, starting on Day 3 at least 48 h after imlifidase administration. Imlifidase: All subjects will receive imlifidase (Day 1) prior to standard care IVIg |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Imlifidase | One (1) dose of imlifidase, 0.25 mg/kg, will be administered IV over 30 minutes, Day 1. IVIg, 0.4 g/kg, will be administered for 5 consecutive Days, starting on Day 3 at least 48 h after imlifidase administration. Imlifidase: All subjects will receive imlifidase (Day 1) prior to standard care IVIg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 1 Grade | Efficacy is assessed as proportion of subjects with improvement of one (1) or more grades in disability outcome on the 6-point GBS DS over time. The 6-point Guillain Barré Syndrome disability score (GBS DS) is a widely accepted and easily obtainable scoring system used to assess disability status of GBS subjects. The DS score is as follows: 0=Healthy, 1=Minor symptoms and capable of running (subjects must be asked to run), 2=Able to walk independently 10 meters or more but unable to run, 3=Able to walk more than 10 meters across an open space with help, 4=Bedridden or chair bound, 5=Needing mechanical ventilation, 6=Dead | The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded. | Posted | Median | Full Range | days | Baseline to Day 360 |
|
Adverse events (AEs) were collected for 1 year (i.e., from the timepoint the patient signed the informed consent form (ICF) until Day 360.
AEs were either spontaneously reported, reported in response to an open question, or revealed by observation.
A treatment-emergent AE (TEAE) is any AE occurring after imlifidase dosing and within 29 days.
The listed non-serious AEs includes both pre-TEAEs, TEAEs and post-TEAEs. 18 SAEs have been reported, 9 of which were treatment-emergent. All SAEs are listed.
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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 | Imlifidase | One (1) dose of imlifidase, 0.25 mg/kg, will be administered IV over 30 minutes, Day 1. IVIg, 0.4 g/kg, will be administered for 5 consecutive Days, starting on Day 3 at least 48 h after imlifidase administration. Imlifidase: All subjects will receive imlifidase (Day 1) prior to standard care IVIg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| False positive investigation result | Investigations | MedDRA (21.1) | Systematic Assessment | Covid false positive |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vice President Research and Development | Hansa Biopharma AB | +4646165670 | info@hansabiopharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 27, 2023 | Feb 25, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 21, 2024 | Feb 25, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D020275 | Guillain-Barre Syndrome |
| ID | Term |
|---|---|
| D011129 | Polyradiculoneuropathy |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| ID | Term |
|---|---|
| C442815 | Mac-1-like protein, Streptococcus |
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Data from patients enrolled in this trial will, if feasible, be compared with an external control group consisting of patients from the IGOS database (International Guillain-Barré Syndrome Outcome Study, ClinicalTrials.gov Identifier: NCT01582763).
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| Mean MRC Sum Score Over Time | Efficacy is assessed as Medical Research Council (MRC) sum score over time. The MRC sum score is widely used to assess the motor impairment in subjects with peripheral neuropathies. It is a sum score of power in 6 muscle groups on each side (abduction of arm, flexion of forearm, extension of the wrist, hip flexion, and extension of knee and dorsal flexion of the foot). The sum of these scores ranges from 0 (total paralysis) to 60 (normal power). It provides valuable information about the muscle strength. Change in MRC sum score helps in identification of GBS patients with treatment related fluctuation or exacerbation. The individual MRC grades are defined as follows: 0=No visible contraction,1=Visible contraction without movement of the limb, 2=Movement of the limb but not against gravity, 3=Movement against gravity (almost full range), 4=Movement against gravity and resistance, 5=Normal | Baseline until Day 180 |
| Change From Baseline in MRC Sum Score Over Time | Efficacy is assessed as change in Medical Research Council (MRC) sum score. The MRC sum score is widely used to assess the motor impairment in subjects with peripheral neuropathies. It is a sum score of power in 6 muscle groups on each side (abduction of arm, flexion of forearm, extension of the wrist, hip flexion, and extension of knee and dorsal flexion of the foot). The sum of these scores ranges from 0 (total paralysis) to 60 (normal power). It provides valuable information about the muscle strength. Change in MRC sum score helps in identification of GBS patients with treatment related fluctuation or exacerbation. The individual MRC grades are defined as follows: 0=No visible contraction,1=Visible contraction without movement of the limb, 2=Movement of the limb but not against gravity, 3=Movement against gravity (almost full range), 4=Movement against gravity and resistance, 5=Normal | Baseline until Day 180 |
| Mean R-ODS Over Time | The patients have rated their ability to perform different common activities using the Rasch-built overall disability score (R-ODS) questionnaire. R-ODS is a linearly weighted disease specific scale, which captures activities and social participation limitation in patients with immune-mediated neuropathies, including GBS. The questionnaire comprises 24 items ranging from ability to read a book or newspaper (as the easiest item to accomplish) to ability to run (most difficult item to accomplish). The response options for each item are: 0=Not possible, 1=Possible with effort, 2=Easy to perform. The obtained raw summed score is subsequently translated to a centile metric ranging from 0 (most severe disability) to 100 (no disability at all). | Baseline to Day 360 |
| Change From Baseline in R-ODS Over Time | The patients have rated their ability to perform different common activities using the Rasch-built overall disability score (R-ODS) questionnaire. R-ODS is a linearly weighted disease specific scale, which captures activities and social participation limitation in patients with immune-mediated neuropathies, including GBS. The questionnaire comprises 24 items ranging from ability to read a book or newspaper (as the easiest item to accomplish) to ability to run (most difficult item to accomplish). The response options for each item are: 0=Not possible, 1=Possible with effort, 2=Easy to perform. The obtained raw summed score is subsequently translated to a centile metric ranging from 0 (most severe disability) to 100 (no disability at all). | Baseline to Day 360 |
| Days in Hospital | The number of days the patients were admitted to hospital | Baseline to Day 360 |
| Time in an ICU | Efficacy is assessed as time in an intensive care unit (ICU) | Baseline until Day 360 |
| Need for Mechanical Ventilation | Baseline until Day 180 |
| Patient's Health State Over Time as Assessed by EQ VAS | Quality of Life will be assessed using the EurQol group's EurQol - 5 dimension (EQ-5D) Health questionnaire. The EQ-5D consists of 2 parts: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ VAS records the patient's self-rated health on a vertical scale, where score 100 is 'The best health you can imagine' and score 0 is the 'The worst health you can imagine'. | Day 8, Day 15, Day 29, Day 57, Day 92, Day 180, and Day 360 |
| Within 2 hours before imlifidase dose until Day 15 |
| PK Profile of Imlifidase: AUC | AUC=Area under the imlifidase plasma concentration versus time curve | Within 2 hours before imlifidase dose until Day 15 |
| PK Profile of Imlifidase: t1/2 | t1/2=Terminal half-life of imlifidase | Within 2 hours before imlifidase dose until Day 15 |
| PK Profile of Imlifidase: CL | CL=Clearance of imlifidase | Within 2 hours before imlifidase dose until Day 15 |
| PK Profile of Imlifidase: V | V=Volume of distribution | Within 2 hours before imlifidase dose until Day 15 |
| Pharmacodynamics - IgG Level in Serum Over Time | The pharmacodynamic (PD) effect of imlifidase is assessed as the elimination of IgG. IgG is cleaved by imlifidase in two steps, the first cut generates single-cleaved IgG (scIgG), and the second cut generates one F(ab')2 fragment and one Fc fragment. The IgG concentration measured in serum using the MSD technology is the sum of intact IgG and scIgG and a decrease in the measured IgG concentration therefore represents complete cleavage of the IgG molecule to Fc and F(ab')2 fragments. For the first 16 patients included in the trial a more frequent PD sampling schedule was conducted. After amending the protocol a less frequent PD sampling schedule was applied. | Within 2 hours before imlifidase dose until Day 15 |
| Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time | Anti-imlifidase IgG antibodies (ADA) in serum. | Within 2 hours before imlifidase dose until Day 180 |
| Bordeaux |
| 33076 |
| France |
| CHU de Limoges - Hôpital Dupuytren | Limoges | 87000 | France |
| Hôpital de la Timone - Centre de référence des maladies neuromusculaires et de la SLA | Marseille | 13385 | France |
| CHU de Montpellier, Hôpital Gui de Chauliac | Montpellier | 34295 | France |
| Centre Hospitalier Universitaire de Nantes | Nantes | 44093 | France |
| Service de neurologie, Hôpitaux Universitaires de Strasbourg | Strasbourg | 67 098 | France |
| Amsterdam UMC | Amsterdam | Netherlands |
| Erasmus Medical Centre | Rotterdam | 3015 GD | Netherlands |
| Queen Elizabeth University Hospital Glasgow | Glasgow | United Kingdom |
| Oxford University Hospital | Oxford | United Kingdom |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body mass index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Imlifidase |
One (1) dose of imlifidase, 0.25 mg/kg, will be administered IV over 30 minutes, Day 1. IVIg, 0.4 g/kg, will be administered for 5 consecutive Days, starting on Day 3 at least 48 h after imlifidase administration. Imlifidase: All subjects will receive imlifidase (Day 1) prior to standard care IVIg |
|
|
| Primary | Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 2 Grades | Efficacy is assessed as proportion of subjects with improvement of one (1) or more grades in disability outcome on the 6-point GBS DS over time. The 6-point Guillain Barré Syndrome disability score (GBS DS) is a widely accepted and easily obtainable scoring system used to assess disability status of GBS subjects. The DS score is as follows: 0=Healthy, 1=Minor symptoms and capable of running (subjects must be asked to run), 2=Able to walk independently 10 meters or more but unable to run, 3=Able to walk more than 10 meters across an open space with help, 4=Bedridden or chair bound, 5=Needing mechanical ventilation, 6=Dead | The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded. | Posted | Median | Full Range | days | Baseline to Day 360 |
|
|
|
| Primary | Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided | Efficacy is assessed as proportion of subjects able to walk unaided (i.e. GBS DS=2) over time | The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded. | Posted | Count of Participants | Participants | Baseline to Day 360 |
|
|
|
| Primary | Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1) | Efficacy is assessed as proportion of patients able to run (i.e. Guillain Barré Syndrome disability score [GBS DS] ≤1) over time | The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded. | Posted | Count of Participants | Participants | Baseline to Day 360 |
|
|
|
| Primary | Mean MRC Sum Score Over Time | Efficacy is assessed as Medical Research Council (MRC) sum score over time. The MRC sum score is widely used to assess the motor impairment in subjects with peripheral neuropathies. It is a sum score of power in 6 muscle groups on each side (abduction of arm, flexion of forearm, extension of the wrist, hip flexion, and extension of knee and dorsal flexion of the foot). The sum of these scores ranges from 0 (total paralysis) to 60 (normal power). It provides valuable information about the muscle strength. Change in MRC sum score helps in identification of GBS patients with treatment related fluctuation or exacerbation. The individual MRC grades are defined as follows: 0=No visible contraction,1=Visible contraction without movement of the limb, 2=Movement of the limb but not against gravity, 3=Movement against gravity (almost full range), 4=Movement against gravity and resistance, 5=Normal | The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded. 26 patients with data at Day 6 and Day 8, 25 patients with data at Day 15 | Posted | Mean | Standard Deviation | score on a scale | Baseline until Day 180 |
|
|
|
| Primary | Change From Baseline in MRC Sum Score Over Time | Efficacy is assessed as change in Medical Research Council (MRC) sum score. The MRC sum score is widely used to assess the motor impairment in subjects with peripheral neuropathies. It is a sum score of power in 6 muscle groups on each side (abduction of arm, flexion of forearm, extension of the wrist, hip flexion, and extension of knee and dorsal flexion of the foot). The sum of these scores ranges from 0 (total paralysis) to 60 (normal power). It provides valuable information about the muscle strength. Change in MRC sum score helps in identification of GBS patients with treatment related fluctuation or exacerbation. The individual MRC grades are defined as follows: 0=No visible contraction,1=Visible contraction without movement of the limb, 2=Movement of the limb but not against gravity, 3=Movement against gravity (almost full range), 4=Movement against gravity and resistance, 5=Normal | The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded. 26 patients with data at Day 6 and Day 8, 25 patients with data at Day 15 | Posted | Mean | Standard Deviation | score on a scale | Baseline until Day 180 |
|
|
|
| Primary | Mean R-ODS Over Time | The patients have rated their ability to perform different common activities using the Rasch-built overall disability score (R-ODS) questionnaire. R-ODS is a linearly weighted disease specific scale, which captures activities and social participation limitation in patients with immune-mediated neuropathies, including GBS. The questionnaire comprises 24 items ranging from ability to read a book or newspaper (as the easiest item to accomplish) to ability to run (most difficult item to accomplish). The response options for each item are: 0=Not possible, 1=Possible with effort, 2=Easy to perform. The obtained raw summed score is subsequently translated to a centile metric ranging from 0 (most severe disability) to 100 (no disability at all). | The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded. 24 patients with data at Day 15, 26 patients with data at Day 8, Day 57, Day 92 and day 360. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Day 360 |
|
|
|
| Primary | Change From Baseline in R-ODS Over Time | The patients have rated their ability to perform different common activities using the Rasch-built overall disability score (R-ODS) questionnaire. R-ODS is a linearly weighted disease specific scale, which captures activities and social participation limitation in patients with immune-mediated neuropathies, including GBS. The questionnaire comprises 24 items ranging from ability to read a book or newspaper (as the easiest item to accomplish) to ability to run (most difficult item to accomplish). The response options for each item are: 0=Not possible, 1=Possible with effort, 2=Easy to perform. The obtained raw summed score is subsequently translated to a centile metric ranging from 0 (most severe disability) to 100 (no disability at all). | The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded. 24 patients with data at Day 15, 26 patients with data at Day 8, Day 57, Day 92 and day 360. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Day 360 |
|
|
|
| Primary | Days in Hospital | The number of days the patients were admitted to hospital | Safety analysis set | Posted | Mean | Standard Deviation | days | Baseline to Day 360 |
|
|
|
| Primary | Time in an ICU | Efficacy is assessed as time in an intensive care unit (ICU) | Safety analysis set | Posted | Count of Participants | Participants | No | Baseline until Day 360 |
|
|
|
| Primary | Need for Mechanical Ventilation | Safety analysis set | Posted | Count of Participants | Participants | No | Baseline until Day 180 |
|
|
|
| Primary | Patient's Health State Over Time as Assessed by EQ VAS | Quality of Life will be assessed using the EurQol group's EurQol - 5 dimension (EQ-5D) Health questionnaire. The EQ-5D consists of 2 parts: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ VAS records the patient's self-rated health on a vertical scale, where score 100 is 'The best health you can imagine' and score 0 is the 'The worst health you can imagine'. | Safety analysis set 27 patients with data at Day 92 and Day180, 26 patients with data at Day 8 and Day 360, 25 patients with data at Day 29 and Day 57, 24 patients with data at Day 15. | Posted | Mean | Standard Deviation | EQ-5D-5L VAS score | Day 8, Day 15, Day 29, Day 57, Day 92, Day 180, and Day 360 |
|
|
|
| Secondary | PK Profile of Imlifidase: Cmax | Cmax=Maximum observed plasma concentration of imlifidase following dosing | Sampling for PK evaluation was performed for the first 16 patients included in the trial | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | Within 2 hours before imlifidase dose until Day 15 |
|
|
|
| Secondary | PK Profile of Imlifidase: Tmax | Tmax=Time point for maximum observed plasma concentration of imlifidase following dosing | Sampling for PK evaluation was performed for the first 16 patients included in the trial. | Posted | Median | Full Range | hours | Within 2 hours before imlifidase dose until Day 15 |
|
|
|
| Secondary | PK Profile of Imlifidase: AUC | AUC=Area under the imlifidase plasma concentration versus time curve | Sampling for PK evaluation was performed for the first 16 patients included in the trial. The time-concentration profile of imlifidase has previously been shown to generally fit a 2-compartment model. 9 out of the 16 patients could be fitted with a 2-compartment model. | Posted | Geometric Mean | Geometric Coefficient of Variation | h×µg/mL | Within 2 hours before imlifidase dose until Day 15 |
|
|
|
| Secondary | PK Profile of Imlifidase: t1/2 | t1/2=Terminal half-life of imlifidase | Sampling for PK evaluation was performed for the first 16 patients included in the trial. The time-concentration profile of imlifidase has previously been shown to generally fit a 2-compartment model. 9 out of the 16 patients could be fitted with a 2-compartment model. Please note, harmonic mean is used for the t½ α and t½ β. | Posted | Mean | Full Range | hours | Within 2 hours before imlifidase dose until Day 15 |
|
|
|
| Secondary | PK Profile of Imlifidase: CL | CL=Clearance of imlifidase | Sampling for PK evaluation was performed for the first 16 patients included in the trial. The time-concentration profile of imlifidase has previously been shown to generally fit a 2-compartment model. 9 out of the 16 patients could be fitted with a 2-compartment model. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/h/kg | Within 2 hours before imlifidase dose until Day 15 |
|
|
|
| Secondary | PK Profile of Imlifidase: V | V=Volume of distribution | Sampling for PK evaluation was performed for the first 16 patients included in the trial. The time-concentration profile of imlifidase has previously been shown to generally fit a 2-compartment model. 9 out of the 16 patients could be fitted with a 2-compartment model. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/kg | Within 2 hours before imlifidase dose until Day 15 |
|
|
|
| Secondary | Pharmacodynamics - IgG Level in Serum Over Time | The pharmacodynamic (PD) effect of imlifidase is assessed as the elimination of IgG. IgG is cleaved by imlifidase in two steps, the first cut generates single-cleaved IgG (scIgG), and the second cut generates one F(ab')2 fragment and one Fc fragment. The IgG concentration measured in serum using the MSD technology is the sum of intact IgG and scIgG and a decrease in the measured IgG concentration therefore represents complete cleavage of the IgG molecule to Fc and F(ab')2 fragments. For the first 16 patients included in the trial a more frequent PD sampling schedule was conducted. After amending the protocol a less frequent PD sampling schedule was applied. | 16 patients analyzed at Day 4, Day 5, Day 6 and Day 7 as the protocol was amended after 16 patients were included and a less frequent PD sampling schedule was applied. | Posted | Mean | Standard Deviation | mg/mL | Within 2 hours before imlifidase dose until Day 15 |
|
|
|
| Secondary | Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time | Anti-imlifidase IgG antibodies (ADA) in serum. | 28 patients have data at Day 29, Day 57, Day 92, and Day 180 | Posted | Mean | Standard Deviation | mg/L | Within 2 hours before imlifidase dose until Day 180 |
|
|
|
| 1 |
| 30 |
| 7 |
| 30 |
| 28 |
| 30 |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Adjustment disorder with depressed mood | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Gastroduodenal ulcer | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Central nervous system inflammation | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Demyelination | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Escherichia bacteraemia | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Faecaloma | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Gastrointestinal motility disorder | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Intestinal pseudo-obstruction | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Corona virus infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Escherichia urinary tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Urinary tract infection bacterial | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Cytomegalovirus infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Enterobacter pneumonia | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Epstein-Barr virus infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Fungal infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Helicobacter infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Klebsiella infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Pneumonia pseudomonal | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Urinary tract infection enterococcal | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Viral rash | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Facial paralysis | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Chronic inflammatory demyelinating polyradiculoneuropathy | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hypersomnia | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Idiopathic intracranial hypertension | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Ischaemic stroke | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Piriformis syndrome | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vocal cord paresis | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Haematocrit decreased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Haemoglobin urine present | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Protein urine present | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Staphylococcus test positive | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Troponin I increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Urine ketone body present | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Folate deficiency | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vitamin B1 deficiency | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hallucination, visual | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
|
| Intensive care unit delirium | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
|
| Venous thrombosis | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
|
| Venous thrombosis limb | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vessel puncture site phlebitis | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Atelectas | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Stridor | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Tracheomalacia | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Autoimmune thyroiditis | Endocrine disorders | MedDRA (21.1) | Systematic Assessment |
|
| Goitre | Endocrine disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA (21.1) | Systematic Assessment |
|
| Inappropriate antidiuretic hormone secretion | Endocrine disorders | MedDRA (21.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
|
| Corneal abrasion | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
|
| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
|
| Subcutaneous haematoma | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Normocytic anaemia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
|
| Eyelid ptosis | Eye disorders | MedDRA (21.1) | Systematic Assessment |
|
| Lagophthalmos | Eye disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hepatocellular injury | Hepatobiliary disorders | MedDRA (21.1) | Systematic Assessment |
|
| Cholestasis | Hepatobiliary disorders | MedDRA (21.1) | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
|
| Prerenal failure | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
|
| Cutaneous calcification | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA (21.1) | Systematic Assessment |
|
At the end of the study, one or more manuscripts for joint publication may be prepared in collaboration between the investigator(s) offered authorship and Hansa Biopharma.
Any confidential information relating to imlifidase or the study, including any data and results from the study will be the exclusive property of Hansa Biopharma AB. The investigators and any other persons involved in the trial will protect the confidentiality of the proprietary information belonging to Hansa Biopharma AB
| D011115 | Polyneuropathies |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D000094025 | Post-Infectious Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|
|
| Day 4 |
|
| Day 5 |
|
| Day 6 |
|
| Day 7 |
|
| Day 8 |
|
| Day 15 |
|
| Day 29 |
|
| Day 57 |
|
| Day 92 |
|
| Day 180 |
|
| Day 360 |
|
| Title | Measurements |
|---|
|
| Day 4 |
|
| Day 5 |
|
| Day 6 |
|
| Day 7 |
|
| Day 8 |
|
| Day 15 |
|
| Day 29 |
|
| Day 57 |
|
| Day 92 |
|
| Day 180 |
|
| Day 360 |
|
|
| Day 4 |
|
|
| Day 6 |
|
|
| Day 8 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 92 |
|
|
| Day 180 |
|
|
|
| Day 6 |
|
|
| Day 8 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 92 |
|
|
| Day 180 |
|
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 92 |
|
|
| Day 180 |
|
|
| Day 360 |
|
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 92 |
|
|
| Day 180 |
|
|
| Day 360 |
|
|
| Title | Measurements |
|---|---|
|
| Admitted 172 days |
|
| Measurements |
|---|
|
| Day 9 to Day 90 and Day 103 to Day 180 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 92 |
|
|
| Day 180 |
|
|
| Day 360 |
|
|
|
| Day 3, before IVIg administration |
|
|
| Day 4, before IVIg administration |
|
|
| Day 5, before IVIg administration |
|
|
| Day 6, before IVIg administration |
|
|
| Day 7, before IVIg administration |
|
|
| Day 8 |
|
|
| Day 15 |
|
|
|
| Day 3, before IVIg administration |
|
|
| Day 8 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 92 |
|
|
| Day 180 |
|
|