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

Primary Purpose

Multifocal Motor Neuropathy

Status

Completed

Phase

Phase 2

Locations

Denmark

Study Type

Interventional

Intervention

HyQvia

Subcuvia

About this trial

This is an interventional treatment trial for Multifocal Motor Neuropathy focused on measuring Subcutaneous immunoglobulin, MMN

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept 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Patients have given written informed consent, prior to the study, with the understanding that consent may be withdrawn at any time without prejudice.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

Sites / Locations

Department of Neurology, Aarhus University Hospital
Department of Neurology, Rigshospitalet

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group A

Group B

Arm Description

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

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

Outcomes

Primary Outcome Measures

Changes in isometric muscle strength

Measurement of isometric muscle strength of four involved muscle groups

Secondary Outcome Measures

Changes in disability score

Disability are evaluated by the use of Guy´s Neurological Disability Scale

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)

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.

Development of hemolytic anemia

Blood samples are drawn at every visit and are analyzed for hemoglobin and related parameters

Development of antibody against hyaluronidase

Blood analyzed for specific antibodies against hyaluronidase

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

Changes in grip strength

Grip strength measured by Jamar® Hand dynamometer

Changes in hand/finger function

9-hole peg test. Standardized test of hand/finger function.

Changes in gait performance

40 meter walk test. Standardized test of walking performance.

Full Information

NCT ID

NCT02556437

First Posted

September 18, 2015

Last Updated

May 14, 2018

Sponsor

Johannes Jakobsen

Collaborators

Baxter Healthcare Corporation

1. Study Identification

Unique Protocol Identification Number

NCT02556437

Brief Title

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

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

June 2016 (undefined)

Primary Completion Date

May 2018 (Actual)

Study Completion Date

May 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Johannes Jakobsen

Collaborators

Baxter Healthcare Corporation

4. Oversight

Data Monitoring Committee

Yes

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multifocal Motor Neuropathy

Keywords

Subcutaneous immunoglobulin, MMN

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A

Arm Type

Experimental

Arm Description

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

Arm Title

Group B

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

HyQvia

Other Intervention Name(s)

Human immunoglobulin

Intervention Description

Human immunoglobulin 10% with recombinant hyaluronidase for subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

Subcuvia

Other Intervention Name(s)

Human immunoglobulin

Intervention Description

Human immunoglobulin 16% for subcutaneous injection

Primary Outcome Measure Information:

Title

Changes in isometric muscle strength

Description

Measurement of isometric muscle strength of four involved muscle groups

Time Frame

Evaluation at week 0, 12, 24, 36, 48

Secondary Outcome Measure Information:

Title

Changes in disability score

Description

Disability are evaluated by the use of Guy´s Neurological Disability Scale

Time Frame

Evaluation at week 0, 12, 24, 36, 48

Title

Changes in clinical evaluation of muscle strength

Description

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)

Time Frame

Evaluation at week 0, 12, 24, 36, 48

Title

Development of Headache and Nausea

Description

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.

Time Frame

During the entire study period

Title

Development of hemolytic anemia

Description

Blood samples are drawn at every visit and are analyzed for hemoglobin and related parameters

Time Frame

Evaluation at week 0, 12, 24, 36, 48

Title

Development of antibody against hyaluronidase

Description

Blood analyzed for specific antibodies against hyaluronidase

Time Frame

Evaluation at week 0, 12, 24, 36, 48

Title

Patient satisfaction

Description

Patient are asked predefined question about satisfaction with the two treatment regimens and score them on a Visual Analogue Scale from 0-100 mm

Time Frame

Evaluation at week: 6, 12, 18, 24, 30, 36, 42, 48

Title

Changes in grip strength

Description

Grip strength measured by Jamar® Hand dynamometer

Time Frame

Evaluation at week 0, 12, 24, 36, 48

Title

Changes in hand/finger function

Description

9-hole peg test. Standardized test of hand/finger function.

Time Frame

Evaluation at week 0, 12, 24, 36, 48

Title

Changes in gait performance

Description

40 meter walk test. Standardized test of walking performance.

Time Frame

Evaluation at week 0, 12, 24, 36, 48

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Johannes Jakobsen, DMSc

Organizational Affiliation

Neuroscience Center, Rigshospitalet

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Neurology, Aarhus University Hospital

City

Aarhus C

ZIP/Postal Code

8000

Country

Denmark

Facility Name

Department of Neurology, Rigshospitalet

City

Copenhagen

ZIP/Postal Code

2100

Country

Denmark

12. IPD Sharing Statement

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

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