Clinical trial NCT02556437: Efficacy and Safety of HyQvia (Immunoglobulin 10% With Recombinant Hyaluronidase) in Multifocal Motor Neuropathy (MMN)
Official title: Randomized, Single-blind, Cross-over Study Investigating the Non-inferiority of Efficacy and Safety of HyQvia in Comparison With Conventional Subcutaneous Ig Therapy in Multifocal Motor Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multifocal Motor Neuropathy
Keywords: Subcutaneous immunoglobulin
MMN
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Baxter Healthcare Corporation
First posted: 2015-09-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of HyQvia (Immunoglobulin 10% with recombinant hyaluronidase) with conventional subcutaneous immunoglobulin treatment in patients with Multifocal Motor Neuropathy (MMN).

Detailed description: Subcutaneous immunoglobulin (SCIG) therapy for MMN is equally efficacious to intravenous immunoglobulin (IGIV), may be self-induced and may induce fewer systemic adverse reactions. Limited SC infusion volumes and reduced bioavailability, however, necessitate multiple infusion sites, more frequent treatment, and dose adjustment to achieve pharmacokinetic equivalence. This is an issue in particular in MMN where relatively high and frequent doses are necessary to maintain long-term improvement of muscle strength. Recombinant human hyaluronidase (rHuPH20) increases subcutaneous tissue permeability and facilitates dispersion and absorption, enabling subcutaneous administration of higher (monthly) doses of Ig. If treatment with HyQvia is at least equally effective and safe as compared with conventional Ig treatment, HyQvia could become the preferred treatment option for patients with MMN as it may have attractive benefits for patients by its mode of administration.

Eligibility criteria: Inclusion Criteria:

* Age at onset 18 - 65 years.
* The 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.
* Decreased or absent tendon reflexes in affected limbs.
* Electrophysiological evidence of one site with definite motor conduction block or one site with probable conduction block according to previously defined criteria.
* Response to SCIG according to criteria that were described in previous studies
* On SCIG maintenance treatment for more than 3 months preceding the study.
* Patients have given written informed consent, prior to the study, with the understanding that consent may be withdrawn at any time without prejudice.

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) practising contraception with an oral contraceptive, intra-uterine device, diaphragm or condom with spermicide or d) being sexually inactive.
* Age \< 18 years

Primary outcomes:
measure: Changes in isometric muscle strength
timeFrame: Evaluation at week 0, 12, 24, 36, 48
Secondary outcomes:
measure: Changes in disability score
timeFrame: Evaluation at week 0, 12, 24, 36, 48
measure: Changes in clinical evaluation of muscle strength
timeFrame: Evaluation at week 0, 12, 24, 36, 48
measure: Development of Headache and Nausea
timeFrame: During the entire study period
measure: Development of hemolytic anemia
timeFrame: Evaluation at week 0, 12, 24, 36, 48
measure: Development of antibody against hyaluronidase
timeFrame: Evaluation at week 0, 12, 24, 36, 48
measure: Patient satisfaction
timeFrame: Evaluation at week: 6, 12, 18, 24, 30, 36, 42, 48
measure: Changes in grip strength
timeFrame: Evaluation at week 0, 12, 24, 36, 48
measure: Changes in hand/finger function
timeFrame: Evaluation at week 0, 12, 24, 36, 48
measure: Changes in gait performance
timeFrame: Evaluation at week 0, 12, 24, 36, 48
Other outcomes:
Locations:
city: Aarhus C
country: Denmark
facility: Department of Neurology, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Neurology, Rigshospitalet
Study officials:
affiliation: Neuroscience Center, Rigshospitalet
name: Johannes Jakobsen, DMSc
role: PRINCIPAL_INVESTIGATOR
References: