Efficacy and Safety of HyQvia (Immunoglobulin 10% With Recombinant Hyaluronidase) in Multifocal Motor Neuropathy (MMN)

Sponsor

Johannes Jakobsen (Other)

Overall Status

Completed

CT.gov ID

NCT02556437

Collaborator

Baxter Healthcare Corporation (Industry)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Multifocal Motor Neuropathy	Drug: HyQvia Drug: Subcuvia	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2016

Actual Primary Completion Date :

May 1, 2018

Actual Study Completion Date :

May 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A 24 weeks of treatment with conventional subcutaneous immunoglobulin (Subcuvia) followed by 24 weeks of treatment with HyQvia	Drug: HyQvia Human immunoglobulin 10% with recombinant hyaluronidase for subcutaneous injection Other Names: Human immunoglobulin Drug: Subcuvia Human immunoglobulin 16% for subcutaneous injection Other Names: Human immunoglobulin
Experimental: Group B 24 weeks of treatment with HyQvia followed by 24 weeks of treatment with conventional subcutaneous immunoglobulin (Subcuvia)	Drug: HyQvia Human immunoglobulin 10% with recombinant hyaluronidase for subcutaneous injection Other Names: Human immunoglobulin Drug: Subcuvia Human immunoglobulin 16% for subcutaneous injection Other Names: Human immunoglobulin

Arm

Intervention/Treatment

Experimental: Group A

24 weeks of treatment with conventional subcutaneous immunoglobulin (Subcuvia) followed by 24 weeks of treatment with HyQvia

Drug: HyQvia

Human immunoglobulin 10% with recombinant hyaluronidase for subcutaneous injection

Other Names:

Human immunoglobulin

Drug: Subcuvia

Human immunoglobulin 16% for subcutaneous injection

Other Names:

Human immunoglobulin

Experimental: Group B

24 weeks of treatment with HyQvia followed by 24 weeks of treatment with conventional subcutaneous immunoglobulin (Subcuvia)

Drug: HyQvia

Human immunoglobulin 10% with recombinant hyaluronidase for subcutaneous injection

Other Names:

Human immunoglobulin

Drug: Subcuvia

Human immunoglobulin 16% for subcutaneous injection

Other Names:

Human immunoglobulin

Outcome Measures

Primary Outcome Measures

Changes in isometric muscle strength [Evaluation at week 0, 12, 24, 36, 48]
Measurement of isometric muscle strength of four involved muscle groups

Secondary Outcome Measures

Changes in disability score [Evaluation at week 0, 12, 24, 36, 48]
Disability are evaluated by the use of Guy´s Neurological Disability Scale
Changes in clinical evaluation of muscle strength [Evaluation at week 0, 12, 24, 36, 48]
Medical Research Council (MRC) sum score of 9 muscle groups bilateral (shoulder abduction, elbow flexion/extension, wrist flexion/extension, hip flexion, knee flexion/extension, ankle dorsal flexion)
Development of Headache and Nausea [During the entire study period]
Participants are asked to register severity of headache and nausea on a VAS scale from 0-100 mm on every day of infusion and the day after.
Development of hemolytic anemia [Evaluation at week 0, 12, 24, 36, 48]
Blood samples are drawn at every visit and are analyzed for hemoglobin and related parameters
Development of antibody against hyaluronidase [Evaluation at week 0, 12, 24, 36, 48]
Blood analyzed for specific antibodies against hyaluronidase
Patient satisfaction [Evaluation at week: 6, 12, 18, 24, 30, 36, 42, 48]
Patient are asked predefined question about satisfaction with the two treatment regimens and score them on a Visual Analogue Scale from 0-100 mm
Changes in grip strength [Evaluation at week 0, 12, 24, 36, 48]
Grip strength measured by Jamar® Hand dynamometer
Changes in hand/finger function [Evaluation at week 0, 12, 24, 36, 48]
9-hole peg test. Standardized test of hand/finger function.
Changes in gait performance [Evaluation at week 0, 12, 24, 36, 48]
40 meter walk test. Standardized test of walking performance.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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