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

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

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).

Study Overview

• Status: Completed
• Conditions: Multifocal Motor Neuropathy
• Intervention / Treatment: Drug: HyQvia; Drug: Subcuvia

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus C, Denmark, 8000
    • Department of Neurology, Aarhus University Hospital
  • Copenhagen, Denmark, 2100
    • Department of Neurology, Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in isometric muscle strength	Measurement of isometric muscle strength of four involved muscle groups	Evaluation at week 0, 12, 24, 36, 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in disability score	Disability are evaluated by the use of Guy´s Neurological Disability Scale	Evaluation at week 0, 12, 24, 36, 48
Changes in clinical evaluation of muscle strength	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)	Evaluation at week 0, 12, 24, 36, 48
Development of Headache and Nausea	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.	During the entire study period
Development of hemolytic anemia	Blood samples are drawn at every visit and are analyzed for hemoglobin and related parameters	Evaluation at week 0, 12, 24, 36, 48
Development of antibody against hyaluronidase	Blood analyzed for specific antibodies against hyaluronidase	Evaluation at week 0, 12, 24, 36, 48
Patient satisfaction	Patient are asked predefined question about satisfaction with the two treatment regimens and score them on a Visual Analogue Scale from 0-100 mm	Evaluation at week: 6, 12, 18, 24, 30, 36, 42, 48
Changes in grip strength	Grip strength measured by Jamar® Hand dynamometer	Evaluation at week 0, 12, 24, 36, 48
Changes in hand/finger function	9-hole peg test. Standardized test of hand/finger function.	Evaluation at week 0, 12, 24, 36, 48
Changes in gait performance	40 meter walk test. Standardized test of walking performance.	Evaluation at week 0, 12, 24, 36, 48

Collaborators and Investigators

• Sponsor: Johannes Jakobsen
• Collaborators: Baxter Healthcare Corporation
• Investigators: Principal Investigator: Johannes Jakobsen, DMSc, Neuroscience Center, Rigshospitalet

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: September 18, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimate): September 22, 2015

Study Record Updates

• Last Update Posted (Actual): May 17, 2018
• Last Update Submitted That Met QC Criteria: May 14, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: MMN; Subcutaneous immunoglobulin
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuritis; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: RH-2015-200