E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic inflammatory demyelinating polyradiculoneuropathy. |
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E.1.1.1 | Medical condition in easily understood language |
nerve disorder leading to loss of muscle strnght and sensibility |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10035325 |
E.1.2 | Term | Plasma immunoglobulin G decreased |
E.1.2 | System Organ Class | 100000004848 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective is to investigate whether high frequency low dosage IVIg treatment is more effective than low frequency high dosage as maintenance treatment for CIDP |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to investigate whether high frequency low dosage of IVIg results in less adverse events compared to low frequency high dosage. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Diagnosis of CIDP or acute-onset CIDP made by a consultant neurologist, fulfilling the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) clinical diagnostic criteria.
2. Age 18 years or older.
3. Significant improvement following the first use of IVIg, defined as a decrease of ≥ 1 grade on the modified Rankin disability scale.
4. To indicate that the patient is still IVIg dependent and has active CIDP, he/she must have shown either an objective deterioration (decrease in muscle strength measured with the vigorimeter and/or MRC sum score following reduction of IVIg dose or lengthening of the IVIg interval or an objective improvement (measured with the vigorimeter and/or MRC sum score) following an increase in IVIg dose or shortening of the IVIg interval at some time during the 9 months before randomisation.
5. Ongoing intermittent treatment with 10% liquid IVIg (Kiovig) for at least 2 infusions. The dose must have been not changed within the 8 weeks prior to the study.
6. EMG findings compatible with CIDP showing peripheral nerve demyelination at least once during their illness.
7. Signed informed consent by the patient. |
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E.4 | Principal exclusion criteria |
1. Known IgA deficiency or known allergic reaction to IVIg.
2. Hand grip strength measured by the Martin Vigorimeter the median value (kPa) for an age and sex matched healthy control.
3. Maintenance dose < 15 gram of IVIg every infusion or an infusion interval < 14 days.
4. Known hereditary neuropathy or severe concomitant diseases such as HIV infection, Lyme disease, chronic active hepatitis, congestive heart failure, systemic lupus erythematosus, drug or toxin induced neuropathy, vasculitis, and malignancies.
5. Multifocal motor neuropathy (MMN), fulfilling the European Federation of Neurological Societies /Peripheral Nerve Society criteria.
6. IgM paraprotein with anti-myelin-associated glycoprotein (MAG) antibodies.
7. Atypical CIDP with pure sensory or persistent unifocal impairment or significant central nervous system involvement.
8. Participation in a controlled trial of an investigational medicinal product within the past 12 weeks.
9. Severe known abnormalities in liver, kidney function or serum glucose level.
10. Treatment with > 20 milligrams of prednisone a day.
11. Treatment with other immunosuppressives (e.g. methotrexate, azathioprine, prednisone) if the dosage has been changed within 8 weeks prior to start of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Hand grip strength (Vigorimeter) will be used as the primary outcome measure. A difference in the (mean of the 4) Vigorimeter changes from baseline between the two groups of > 8 kPa (mean of both hands) is considered clinically relevant. A difference of > 8 kPa in Vigorimeter change from baseline in favour of the group treated with half the dosage and interval as compared with the other treatment group will be considered a clinical relevant improvement. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Hand grip strenght will be measusured before very infusion, and this endpoint will be evaluated at the end of the trial. |
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E.5.2 | Secondary end point(s) |
Changes in the R-ODSS, R-FSS, and SF-36 will be used as secondary outcome measures. The secondary objective will be to record the occurrence of side-effects. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Questionnaires will be filled-in just before every infusion, and this endpoint will be evaluated at the end of the trial. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
comparator is a different dosing schedule of the same drug. placebo is added to maintain the blind o |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |