E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multifocal Motor Neuropathy (MMN) |
Multifokal Motor Neuropati (MMN) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic inflammatory motoric neuropathy |
Kronisk inflammatorisk nervebetændelse |
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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 | PT |
E.1.2 | Classification code | 10064135 |
E.1.2 | Term | Polyneuropathy chronic |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
To assess the efficacy of immunoglobulin administered together with hyaluronidase (HyQvia) in large doses subcutaneously compared to conventional treatment with subcutaneous immunoglobulin (Subcuvia) in patients with MMN |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of HyQvia in patients with MMN |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Presence of asymmetrical limb weakness at onset or motor involvement having a motor nerve distribution in at least two peripheral nerve distributions, predominant upper limb involvement, disabling weakness MRC grade 4 or less in at least one muscle group.
Decreased or absent tendon reflexes in affected limbs.
Electrophysiological evidence of one site with definite motor conduction block or one site with propable conduction block according to previously defined criteria.
Response to subcutaneous immunoglobulin according to criteria described in previous studies.
On subcutaneous immunoglobulin maintenance treatment prior to enrolment.
Age at onset 18-65 years. |
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E.4 | Principal exclusion criteria |
Bulbar signs or symptoms.
Upper motor neuron signs (spasticity, hyperreflexia, extensor plantar response).
Sensory symptoms and signs with sensory deficits on examination (except for vibration sense) and abnormal results of sensory nerve conduction studies.
Other neuropathies (e.g. diabetic, lead, porphyric or vasculitic neuropathy, chronic inflammatory demyelinating polyneuropathy, Lyme neuroborreliosis, post radiation neuropathy, hereditary neuropathy with liability to pressure palsies, Charcot-Marie-Tooth neuropathies, meningeal carcinomatosis).
Treatment with other immunosuppressive drugs (cyclophosphamide, azathioprine, cyclosporin) in the 6 months preceding the study.
Female patient who is pregnant or breast-feeding or of childbearing potential.
Confirmation that the patient is not pregnant will be established by a negative b-HCG test within a 7-day period before inclusion in the study. Lack of childbearing potential is met by a) being post-menopausal, b) being surgically sterile, c) practicing contraception with an oral contraceptive, intra-uterine device, diaphragm or condom with spermacide or d) being sexually inactive. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in muscle strength during treatment with HyQvia vs Subcuviaevaluated by isometric dynamometry.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Group A: 24 weeks of Subcuvia treatment followed by 24 weeks of HyQvia treatment
Timepoints for clinical examination: Week 0, 12, 24, 36 and 48
Telephone interview according to side effects and compliance: Week 6, 18, 30 and 42
Group B: 24 weeks of HyQvia treatment followed by 24 weeks of Subcuvia treatment
Timepoints for clinical examination: Week 0, 12, 24, 36 and 48
Telephone interview according to side effects and compliance: Week 6, 18, 30 and 42
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E.5.2 | Secondary end point(s) |
Changes in muscle strength during treatment with HyQvia vs Subcuvia evaluated by hand held dynamometry (grip strength) and clinical examination.
Changes in disability score during treatment with HyQvia vs Subcuvia, evaluated by Guy’s Neurological Disability Scale and the self-evaluation scale.
Changes in physical function and performance during treatment with HyQvia vs Subcuvia, evaluated by 9-hole-peg test and 40 meter-walk-test.
Development and severity of headache and nausea during treatment with HyQvia, evaluated by questionnaire
Development of hemolytic anemia during treatment, evaluated by blood analysis
Development of antibody against hyaluronidase during treatment with HyQvia, evaluated by blood analysis
Patient satisfaction, evaluated by questionnaire
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Group A: 24 weeks of Subcuvia treatment followed by 24 weeks of HyQvia treatment
Timepoints for clinical examination: Week 0, 12, 24, 36 and 48
Telephone interview according to side effects and compliance: Week 6, 18, 30 and 42
Group B: 24 weeks of HyQvia treatment followed by 24 weeks of Subcuvia treatment
Timepoints for clinical examination: Week 0, 12, 24, 36 and 48
Telephone interview according to side effects and compliance: Week 6, 18, 30 and 42
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 2 |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |