Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy
Conditions
Keywords
Chronic Inflammatory Demyelinating Poly Neuropathy (CIDP)
Brief summary
Study to evaluate the Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy
Detailed description
Prospective, Double-blind, Randomized, Multicenter Phase III Study Evaluating Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy (ProCID trial)
Interventions
DRUGNewGam
In the Dose-evaluation Phase, all patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (0.5, 1.0 or 2.0 g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). If a patient is randomized to receive the low or medium NewGam dose, the same volume with the same infusion rate as would have been applied in case the patient would have been randomized to 2.0 g/kg NewGam will be used, thus supplemented with an authorized 0.9% w/v isotonic sodium chloride solution as appropriate and detailed in the following infusion bag split to maintain the blinding
Sponsors
Octapharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with diagnosis of definite or probable Chronic inflammatory demyelinating polyneuropathy (CIDP) according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) Guideline 2010 \[van den Bergh et al., 2010\]; including patients with Multifocal Acquired Demyelinating Sensory And Motor Neuropathy (MADSAM) or pure motor Chronic inflammatory demyelinating polyneuropathy (CIDP ) 2. Patients currently depending on treatment with immunoglobulins or corticosteroids 3. Patients with active disease, i.e. not being in remission, who are progressive or relapsing prior to trial start or during the Wash-out Phase 4. Weakness of at least 2 limbs 5. \>18 to \<80 years of age 6. Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score between 2 and 9 (with a score of 2 coming exclusively from leg disability) 7. Voluntarily given, fully informed written consent obtained from patient before any study-related procedures are conducted
Exclusion criteria
1. Unifocal forms of Chronic inflammatory demyelinating polyneuropathy (CIDP) 2. Pure sensory Chronic inflammatory demyelinating polyneuropathy (CIDP) 3. Multifocal motor neuropathy (MMN) with conduction block \[van den Bergh et al., 2010\] 4. Patients who previously failed immunoglobulin treatment 5. Treatment with immunomodulatory/suppressive agents (cyclosporin, methotrexate, mitoxantrone, mycophenolate mofetil or azathioprine) during the six months prior to baseline visit 6. Patients on or treated with rituximab, alemtuzumab, cyclophosphamide, or other intensive chemotherapeutic regimens, previous lymphoid irradiation or stem cell transplantation during the 12 months prior to baseline visit 7. Respiratory impairment requiring mechanical ventilation 8. Myelopathy or evidence of central nervous system demyelination or significant persisting neurological deficits from stroke, or central nervous system (CNS) trauma 9. Clinical evidence of peripheral neuropathy from another cause such as 1. connective tissue disease or systemic lupus erythematosus (SLE) 2. HIV infection, hepatitis, Lyme disease 3. cancer (with the exception of basal cell skin cancer) 4. IgM paraproteinemia with anti-myelin associated glycoprotein antibodies 10. Diabetic neuropathy 11. Cardiac insufficiency (New York Heart Association \[NYHA\] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease 12. Severe liver disease (ALAT 3x \> normal value) 13. Severe kidney disease (creatinine 1.5x \> normal value) 14. Hepatitis B, hepatitis C or HIV infection 15. Thromboembolic events: patients with a history of deep vein thrombosis (DVT) within the last year prior to baseline visit or pulmonary embolism ever; patients with susceptibility to embolism or deep vein thrombosis (DVT) 16. Body mass index (BMI) ≥40 kg/m2 17. Patients with uncompensated hypothyroidism (abnormally high Thyroid-Stimulating Hormone \[TSH\] and abnormally low Thyroxine \[T4\]) or known vitamin B12 deficiency if patients don't receive adequate substitution therapy 18. Medical conditions whose symptoms and effects could alter protein catabolism and/or Immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome) 19. Known Immunoglobulin A (IgA) deficiency with antibodies to Immunoglobulin A (IgA) 20. History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of NewGam 21. Known blood hyperviscosity, or other hypercoagulable states 22. Use of other blood or plasma-derived products within three months prior to Visit 2 23. Patients with a past or present history of drug abuse or alcohol abuse within the preceding five years prior to baseline visit 24. Patients unable or unwilling to understand or comply with the study protocol 25. Participation in another interventional clinical study with investigational medicinal product (IMP) treatment currently or during the three months prior to Visit 2 26. Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to use an effective birth control method (such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner) while on study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | at Week 24 | Efficacy - Proportion of responders in the 1.0 g/kg NewGam arm at Week 24 (Termination Visit) relative to baseline (Week 0). A responder being defined as a patient with a decrease of at least 1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (a scale from 0 to 10, from healthy to unable to make any purposeful movements with arms and/or legs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | at Week 24 | Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline compared to the 1.0 g/kg arm, based on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score |
| Grip Strength Score | at Week 24 | Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline at Week 0 compared to the 1.0 g/kg arm, based on the grip strength (Martin Vigorimeter) using the previously published minimum clinically important difference (MCID) cut-off of 8 kilopascal (kPa) |
| Inflammatory Rasch-built Overall Disability Scale (I-RODS Score) | at Week 24 | Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline at Week 0 compared to the 1.0 g/kg arm, based on the Inflammatory Rasch-built overall disability scale (I-RODS Score) using the MCID concept related to the varying standard errors (MCID-SE) as recently demonstrated |
| Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | Week 24 | Time to first confirmed worsening on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale by at least 1 point from the value at baseline (Week 0) |
| Inflammatory Rasch-built Overall Disability Scale (I-RODS) | Up to 24 weeks | Mean change from baseline (Week 0) to Termination Visit in Inflammatory Rasch-built overall disability sum score (I-RODS using the concept of MCID-SE as recently reported) and number of improvers. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. A scale from 0 to 48, from Not possible to perform to Possible without any difficulty. Higher values represent a better outcome. |
| Mean Change in Grip Strength | Up to 24 weeks | Mean change from baseline (Week 0) to Termination Visit in grip strength of both hands (assessed by Martin vigorimeter). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. |
| Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale) | Up to 24 weeks | Mean change from baseline (Week 0) to Termination Visit in Pain Intensity Numeric Rating Scale (PI-NRS). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. The Pain Intensity Numeric Rating Scale (PI-NRS, a numeric scale where 0 = no pain and 10 = worst possible pain) is an 11-point scale for patient self-reporting of pain. A higher value represents a worse outcome. |
| Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | 24 weeks | Time to first confirmed worsening on the I-RODS scale. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. A scale from 0 to 48, from Not possible to perform to Possible without any difficulty. Higher values represent a better outcome. Worsening is determined using the concept of MCID (minimum clinically important difference) using the individually obtained standard errors (MCID-SE). |
| 1 Point Decrease in the INCAT Disability Score | 24 weeks | Time to 1 point decrease (improvement of disability) in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score |
| Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | 24 weeks | Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS) scores |
| Motor Nerves | Up to 24 weeks | Mean change from baseline (Week 0) to Termination Visit in sum of the distal evoked amplitude of 4 right sided and 4 left sided motor nerves (peroneal, tibial, ulnar and median). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. |
Countries
Bulgaria, Canada, Czechia, Germany, Hungary, Poland, Romania, Russia, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.5 g/kg NewGam All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (0.5g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). | 35 |
| 1.0 g/kg NewGam All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (1.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). | 69 |
| 2.0 g/kg NewGam All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (2.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). | 38 |
| Total | 142 |
Baseline characteristics
| Characteristic | 0.5 g/kg NewGam | 1.0 g/kg NewGam | 2.0 g/kg NewGam | Total |
|---|---|---|---|---|
| Age, Continuous | 52.49 years STANDARD_DEVIATION 14.449 | 56.32 years STANDARD_DEVIATION 14.616 | 58.05 years STANDARD_DEVIATION 13.764 | 55.84 years STANDARD_DEVIATION 14.398 |
| BMI | 27.92 kg/m^2 STANDARD_DEVIATION 4.873 | 27.27 kg/m^2 STANDARD_DEVIATION 4.588 | 26.33 kg/m^2 STANDARD_DEVIATION 5.231 | 27.18 kg/m^2 STANDARD_DEVIATION 4.837 |
| Height | 173.46 cm STANDARD_DEVIATION 9.506 | 172.81 cm STANDARD_DEVIATION 8.304 | 171.61 cm STANDARD_DEVIATION 9.03 | 172.65 cm STANDARD_DEVIATION 8.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 69 Participants | 38 Participants | 142 Participants |
| Sex: Female, Male Female | 13 Participants | 31 Participants | 14 Participants | 58 Participants |
| Sex: Female, Male Male | 22 Participants | 38 Participants | 24 Participants | 84 Participants |
| Weight | 84.09 kg STANDARD_DEVIATION 16.511 | 81.74 kg STANDARD_DEVIATION 16.333 | 77.68 kg STANDARD_DEVIATION 75.5 | 81.23 kg STANDARD_DEVIATION 79 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 1 / 69 | 1 / 38 | 2 / 142 |
| other Total, other adverse events | 20 / 35 | 45 / 69 | 24 / 38 | 88 / 142 |
| serious Total, serious adverse events | 1 / 35 | 4 / 69 | 1 / 38 | 6 / 142 |
Outcome results
Primary
Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Efficacy - Proportion of responders in the 1.0 g/kg NewGam arm at Week 24 (Termination Visit) relative to baseline (Week 0). A responder being defined as a patient with a decrease of at least 1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (a scale from 0 to 10, from healthy to unable to make any purposeful movements with arms and/or legs)
Time frame: at Week 24
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.0 g/kg NewGam | Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | .7971 proportion of subjects |
Secondary
1 Point Decrease in the INCAT Disability Score
Time to 1 point decrease (improvement of disability) in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score
Time frame: 24 weeks
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.0 g/kg NewGam | 1 Point Decrease in the INCAT Disability Score | 22.0 days |
| 1.0 g/kg NewGam | 1 Point Decrease in the INCAT Disability Score | 26.0 days |
| 2.0 g/kg NewGam | 1 Point Decrease in the INCAT Disability Score | 23.0 days |
Secondary
Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)
Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS) scores
Time frame: 24 weeks
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.0 g/kg NewGam | Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | NA days |
| 1.0 g/kg NewGam | Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | NA days |
| 2.0 g/kg NewGam | Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | NA days |
Secondary
Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline compared to the 1.0 g/kg arm, based on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score
Time frame: at Week 24
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.0 g/kg NewGam | Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | .6471 Proportion of responders |
| 1.0 g/kg NewGam | Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | .7971 Proportion of responders |
| 2.0 g/kg NewGam | Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | .9167 Proportion of responders |
Secondary
Grip Strength Score
Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline at Week 0 compared to the 1.0 g/kg arm, based on the grip strength (Martin Vigorimeter) using the previously published minimum clinically important difference (MCID) cut-off of 8 kilopascal (kPa)
Time frame: at Week 24
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.0 g/kg NewGam | Grip Strength Score | .5588 Proportion of responders |
| 1.0 g/kg NewGam | Grip Strength Score | .6522 Proportion of responders |
| 2.0 g/kg NewGam | Grip Strength Score | .8333 Proportion of responders |
Secondary
Inflammatory Rasch-built Overall Disability Scale (I-RODS)
Mean change from baseline (Week 0) to Termination Visit in Inflammatory Rasch-built overall disability sum score (I-RODS using the concept of MCID-SE as recently reported) and number of improvers. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. A scale from 0 to 48, from Not possible to perform to Possible without any difficulty. Higher values represent a better outcome.
Time frame: Up to 24 weeks
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.0 g/kg NewGam | Inflammatory Rasch-built Overall Disability Scale (I-RODS) | 11.38 score on a scale | Standard Deviation 12.485 |
| 1.0 g/kg NewGam | Inflammatory Rasch-built Overall Disability Scale (I-RODS) | 10.32 score on a scale | Standard Deviation 10.836 |
| 2.0 g/kg NewGam | Inflammatory Rasch-built Overall Disability Scale (I-RODS) | 13.86 score on a scale | Standard Deviation 11.981 |
Secondary
Inflammatory Rasch-built Overall Disability Scale (I-RODS Score)
Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline at Week 0 compared to the 1.0 g/kg arm, based on the Inflammatory Rasch-built overall disability scale (I-RODS Score) using the MCID concept related to the varying standard errors (MCID-SE) as recently demonstrated
Time frame: at Week 24
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.0 g/kg NewGam | Inflammatory Rasch-built Overall Disability Scale (I-RODS Score) | .3824 Proportion of responders |
| 1.0 g/kg NewGam | Inflammatory Rasch-built Overall Disability Scale (I-RODS Score) | .5507 Proportion of responders |
| 2.0 g/kg NewGam | Inflammatory Rasch-built Overall Disability Scale (I-RODS Score) | .7222 Proportion of responders |
Secondary
Mean Change in Grip Strength
Mean change from baseline (Week 0) to Termination Visit in grip strength of both hands (assessed by Martin vigorimeter). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
Time frame: Up to 24 weeks
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0 g/kg NewGam | Mean Change in Grip Strength | Dominant Hand | 23.91 kPa | Standard Deviation 25.29 |
| 1.0 g/kg NewGam | Mean Change in Grip Strength | Non-dominant Hand | 23.94 kPa | Standard Deviation 24.6 |
| 1.0 g/kg NewGam | Mean Change in Grip Strength | Dominant Hand | 19.38 kPa | Standard Deviation 20.377 |
| 1.0 g/kg NewGam | Mean Change in Grip Strength | Non-dominant Hand | 17.43 kPa | Standard Deviation 19.916 |
| 2.0 g/kg NewGam | Mean Change in Grip Strength | Dominant Hand | 26.06 kPa | Standard Deviation 25.03 |
| 2.0 g/kg NewGam | Mean Change in Grip Strength | Non-dominant Hand | 24.53 kPa | Standard Deviation 22.247 |
Secondary
Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale)
Mean change from baseline (Week 0) to Termination Visit in Pain Intensity Numeric Rating Scale (PI-NRS). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. The Pain Intensity Numeric Rating Scale (PI-NRS, a numeric scale where 0 = no pain and 10 = worst possible pain) is an 11-point scale for patient self-reporting of pain. A higher value represents a worse outcome.
Time frame: Up to 24 weeks
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.0 g/kg NewGam | Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale) | -2.29 score on a scale | Standard Deviation 3.04 |
| 1.0 g/kg NewGam | Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale) | -2.19 score on a scale | Standard Deviation 2.907 |
| 2.0 g/kg NewGam | Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale) | -2.17 score on a scale | Standard Deviation 3.256 |
Secondary
Motor Nerves
Mean change from baseline (Week 0) to Termination Visit in sum of the distal evoked amplitude of 4 right sided and 4 left sided motor nerves (peroneal, tibial, ulnar and median). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
Time frame: Up to 24 weeks
Population: Intention-to-treat Set (ITTS): The ITTS consist of all patients of the Safety Data Set for whom any data was collected post infusion of IMP. Three patients (one in the 0.5 g/kg group and two in the 2.0 g/kg group) were excluded from the ITTS as no data were collected post-infusion of IMP. Therefore n=139 for the ITTS. Every treated subject will be considered in the analysis according to his randomized treatment/dose assignment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.0 g/kg NewGam | Motor Nerves | 2.16 mV | Standard Deviation 6.332 |
| 1.0 g/kg NewGam | Motor Nerves | 2.69 mV | Standard Deviation 6.688 |
| 2.0 g/kg NewGam | Motor Nerves | 3.93 mV | Standard Deviation 9.298 |
Secondary
Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
Time to first confirmed worsening on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale by at least 1 point from the value at baseline (Week 0)
Time frame: Week 24
Population: There was only 1 patient with worsening (in the 1.0 g/kg group), thus an analysis of the time to first worsening was not possible.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.0 g/kg NewGam | Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | NA days |
| 1.0 g/kg NewGam | Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | NA days |
| 2.0 g/kg NewGam | Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | NA days |
Secondary
Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)
Time to first confirmed worsening on the I-RODS scale. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. A scale from 0 to 48, from Not possible to perform to Possible without any difficulty. Higher values represent a better outcome. Worsening is determined using the concept of MCID (minimum clinically important difference) using the individually obtained standard errors (MCID-SE).
Time frame: 24 weeks
Population: There was 1 patient with worsening in the 0.5 g/kg group and 2 in the 1.0 g/kg group; an analysis of the time to first worsening was not possible
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1.0 g/kg NewGam | Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | NA days |
| 1.0 g/kg NewGam | Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | NA days |
| 2.0 g/kg NewGam | Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | NA days |