Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Neoplasm Metastasis

Abortion, Spontaneous

Abortion, Habitual

Disease Attributes

Neoplastic Processes

Pregnancy Complications

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

All Drugs and Chemicals

Antibodies

Immunoglobulins

Immunoglobulins, Intravenous

gamma-Globulins

Rho(D) Immune Globulin

Immunologic Factors

Repeated infusions of intravenous immunoglobulin in early pregnancy

Intravenous infusions, 25-35 g each time, 4th to 15th gestational week

Intravenous immunoglobulin

Repeated infusions of Human Albumin 5%, 250-350 ml between 4th and 15th gestational week

Human albumin

Ole B. Christiansen, MD, D.M.Sc.

The investigators want to test whether infusions of intravenous immunoglobulin - a blood product known to modify immune responses - in early pregnancy will increase the chance of a subsequent live birth in women with three or more miscarriages after a birth and a total of at least four miscarriages. This will be done in a trial where 82 patients will be randomly allocated to infusions with intravenous immunoglobulin or placebo during pregnancy.

Trial of the Efficacy of Intravenous Immunoglobulin for Treating Women With Unexplained Secondary Recurrent Miscarriage

A Randomized, Placebo-controlled, Double-blind Trial of Intravenous Immunoglobulin for Women With Unexplained Secondary Recurrent Miscarriage

The Ministry of Science, Technology and Innovation, Denmark

Rigshospitalet, Denmark

consultant

Nervous System Diseases

Immune System Diseases

Musculoskeletal Diseases

Rare Diseases

Myasthenia Gravis

Muscle Weakness

Paresis

Asthenia

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Immunoglobulin G

This group of MG patients will start with 2g/kg of IVIG on month 1, 1 g/kg of IVIG 4 and then 8 weeks later, and within 2 weeks switch to SCIG treatment

This group of MG patients will start with SCIG alone

subcutaneous immunoglobulin (SCIG)

10% intravenous immunoglobulin + 20% subcutaneous immunoglobulin

intravenous immunoglobulin + subcutaneous immunoglobulin (SCIG)

Eduardo Ng, MD

Hans Katzberg, MD

This is a prospective open-label, randomized, parallel arm clinical trial.

The primary objective of the study is to evaluate the safety and efficacy of Cuvitru 20% subcutaneous immunoglobulin in patients with myasthenia gravis (MG). The secondary objective is to evaluate patient preferences and effects on quality of life when treating MG patients with SCIG. Exploratory objectives are to compare de novo administration starting SCIG directly with those starting with a loading dose of IVIG followed by SCIG administration.

Patients over age 18 with moderate to severe MG with MGFA Class II-IV without contraindications to immunoglobulin will be considered for the study.

All patients will be eligible to enter either arm of the study, Arm 1: 10% Gammagard IVIG followed by 20% Cuvitry SCIG and Arm 2: Cuvitru 20% SCIG alone.

Myasthenia gravis (MG) is an autoimmune neuromuscular condition which can cause fatigable weakness of skeletal muscles including bulbar, ocular, limb, axial and respiratory muscles. Symptoms range from mild, transient double vision and ptosis to severe, life threatening diffuse weakness, and treatments which are immunosuppressive or immunomodulatory have been shown to improve outcome in MG. This includes 10% intravenous immunoglobulin (IVIG), which has previous been shown by our group to improve strength at 2 and 4 weeks in patients with MG. Due to delay in the onset of many immunosuppressives and potential side effects from steroids and other immunosuppressive medications, IVIG is also used in clinical practice as bridging of maintenance therapy until other therapies take effect or the patient stabilizes. In addition, there have been other studies suggesting that 20% subcutaneous immunoglobuin (SCIG) can be helpful to improve strength in patients with MG over a relatively short period of time (6 weeks). Some of these studies are ongoing and are further evaluating the ability of IVIG and SCIG to stabilize or improve strength IVIG in patients with MG, however, there is no current published study evaluating different administration routes of immunoglobulin (IVIG and SCIG) in patients with MG over a longer 6 month follow-up period.

The current study aims to be the first to evaluate 20% Cuvitru SCIG formulation in patients with neuromuscular conditions including MG. The study aim is to evaluate the safety and efficacy of 6 months of 20% SCIG Cuvitru treatment vs three months of 10% IVIG "pre-treatment" followed by 3 months of 20% SCIG Cuvitru treatment. The study will also be the first to use the myasthenia gravis impairment index (MGII) as primary outcome in conjunction with standard MG outcomes.

Subcutaneous Immunoglobulin for Myasthenia Gravis

Efficacy and Safety of Subcutaneous Immunoglobulin in Patients With Myasthenia Gravis

Change in the Myasthenia Gravis Impairment Index (score 0-84, with 84 being the maximal score indicating the most severe MG status) at baseline compared to end of study

Change in the Quantitative Myasthenia Gravis Score (score 0-39, with 39 indicating the most severe clinical findings related to MG) at baseline compared to end of study

Change in the MG Activities of Daily Living (score 0-24, with 24 indicating the most severe clinical findings related to MG) at baseline compared to end of study

Change in the Myasthenia Gravis Composite Score (score 0-50, with 50 indicating the most severe clinical findings related to MG) at baseline compared to end of study) at baseline compared to end of study

Change in the 15-Item Myasthenia Gravis Quality of Life Score (score 0-45, with 45 indicating the most severe clinical findings related to MG) at baseline compared to end of study) at baseline compared to end of study

All the above outcomes including the myasthenia gravis impairment index, quantitative myasthenia gravis score, myasthenia gravis activities of daily living, myasthenia gravis composite score, myasthenia gravis quality of life 15 score in patients receiving de novo administration starting SCIG directly with those starting with a loading dose of IVIG followed by SCIG administration will be compared.

o evaluate the adverse event profile of high dose (20% Cuvitru) SCIG in MG and compare this with existing published adverse events of 20% high-dose SCIG in neuromuscular diseases. Specifically the total number of adverse events as defined in Part C, Division 5 of the Health Canada Food and Drug Regulations will be compared to existing published adverse events of 20% SCIG and the total number of adverse events occuring in the IVIG vs SCIG arms will also be compared.

University Health Network, Toronto

Neurologist, Principle Investigator

Eye Diseases

Infections

Neuromyelitis Optica

Myelitis

Myelitis, Transverse

Demyelinating Autoimmune Diseases, CNS

Neuritis

Optic Neuritis

Optic Nerve Diseases

Cranial Nerve Diseases

Demyelinating Diseases

Communicable Diseases

Central Nervous System Infections

Central Nervous System Diseases

Spinal Cord Diseases

Neuroinflammatory Diseases

Neuromyelitis Optica Spectrum Disorder

Transverse Myelitis

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Paediatric patients - 30mg/kg or 500mg/m2 up to a maximum daily dose of 1g/day for 5 days.

Adult patients - 1g/day for 5 days.

Paediatric patients \<41.2kg - total dose of 2g/kg in divided doses over 2 days.

All other patients - total dose of 2g/kg in divided doses over 5 days.

PLUS Intravenous Methylprednisolone

Pediatric patients - 30mg/kg or 500mg/m2 up to a maximum daily dose of 1g/day for 5 days.

Adult patients - 1g/day for 5 days.

Intravenous Methylprednisolone

Intravenous Immunoglobulin

Ming Lim, MB, PhD

This multi-center randomized controlled trial evaluates if the addition of intravenous immunoglobulin to standard treatment of corticosteroids improves outcome in children and adults with first episode of Transverse Myelitis of Neuro-myelitis optica. Half of participants will receive corticosteroids alone, whilst the other half will receive corticosteroids plus intravenous immunoglobulin.

Transverse myelitis (TM) is a severe demyelinating condition predominantly affecting young people, which causes significant long-term disability in approximately one third. Current initial treatment is with corticosteroids, although evidence for their use is based on extrapolation from trials in adult multiple sclerosis relapses. In view of the severity of the condition, additional treatments have been trialed.

Intravenous immunoglobulin (IVIG) is often used as second-line treatment in steroid-unresponsive central nervous system demyelination, although evidence for its efficacy is limited to small case series and case reports. Randomized controlled trials have demonstrated that IVIG reduces inflammation and enhances remyelination in a number of neurological conditions, although there have been no randomized controlled trials testing its use in adults and children with TM.

This study will evaluate if additional and early treatment with IVIG is of extra benefit in TM when compared to the current standard therapy of intravenous steroids alone.

A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin Versus Standard Therapy for Transverse Myelitis

A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin (IVIg) Versus Standard Therapy for the Treatment of Transverse Myelitis in Adults and Children

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of the Efficacy of Intravenous Immunoglobulin for Treating Women With Unexplained Secondary Recurrent Miscarriage	NCT00722475	Secondary Recur...	Intravenous imm... Human albumin	18 Years - 40 Years	Rigshospitalet, Denmark
Subcutaneous Immunoglobulin for Myasthenia Gravis	NCT04728425	Myasthenia Grav...	subcutaneous im... intravenous imm...	18 Years - 100 Years	University Health Network, Toronto
A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin Versus Standard Therapy for Transverse Myelitis	NCT02398994	Myelitis, Trans... Neuromyelitis O...	Intravenous Met... Intravenous Imm...	1 Year -	Guy's and St Thomas' NHS Foundation Trust
Trial of the Efficacy of Intravenous Immunoglobulin for Treating Women With Unexplained Secondary Recurrent Miscarriage	NCT00722475	Secondary Recur...	Intravenous imm... Human albumin	18 Years - 40 Years	Rigshospitalet, Denmark
Subcutaneous Immunoglobulin for Myasthenia Gravis	NCT04728425	Myasthenia Grav...	subcutaneous im... intravenous imm...	18 Years - 100 Years	University Health Network, Toronto
A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin Versus Standard Therapy for Transverse Myelitis	NCT02398994	Myelitis, Trans... Neuromyelitis O...	Intravenous Met... Intravenous Imm...	1 Year -	Guy's and St Thomas' NHS Foundation Trust

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