Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Treatment With Subcutaneous Immunoglobulin (IgPro20) - Full Text View

Purpose

This is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group 3-arm study to investigate 2 different doses of subcutaneous (SC) IgPro20 compared with placebo for maintenance treatment of patients with CIDP.

Patients who received at lease 1 dose of intravenous immunoglobulin (IVIG) within 8 weeks before screening will be assessed during 4 separate study periods. Patients first undergo a Screening Period, followed by an IgG Dependency Test Period of up to 12 weeks to test for ongoing need of IgG. Those patients experiencing CIDP relapse during this test period will be administered a standardized IVIG regimen during an IVIG Re-stabilization Period. Patients with improved and maintained adjusted inflammatory neuropathy cause and treatment scale (INCAT) in the IVIG Re-stabilization Period will continue to the SC Treatment Period of the study. Patients entering the 24 week SC Treatment Period will be randomized to receive weekly infusions of 1 of 2 IgPro20 doses (0.2 or 0.4 g/kg body weight) or placebo.

The overall study duration is up to 52 weeks. Clinical outcomes will be assessed by the Inflammatory Neuropathy Cause and Treatment (INCAT) score, maximum grip strength, the Medical Research Council (MRC) sum score, the Rasch-built Overall Disability Scale (R-ODS), and electrophysiological evaluations.

Condition	Intervention	Phase
Chronic Inflammatory Demyelinating Polyneuropathy Polyradiculoneuropathy	Biological: IgPro20 Biological: Placebo Biological: IgPro10	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Randomized, Multicenter, Double-blind, Placebo-controlled, Parallel-group Phase III Study to Investigate the Efficacy, Safety, and Tolerability of 2 Different Doses of IgPro20 (Subcutaneous Immunoglobulin) for the Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) - the PATH Study

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Chronic Inflammatory Demyelinating Polyneuropathy

U.S. FDA Resources

Further study details as provided by CSL Behring:

Primary Outcome Measures:

Percentage (%) of subjects who relapse or are withdrawn for any other reason during the SC treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Relapse is defined as an increase of at least 1 INCAT score point (except for the increase from 0 to 1 in the upper limb score).

Secondary Outcome Measures:

Change in mean Inflammatory Neuropathy Cause and Treatment (INCAT) scores during the SC treatment period [ Time Frame: At baseline and at all visits during the 25-week SC Treatment Period ] [ Designated as safety issue: No ]
Change in mean maximum grip strength scores during the SC treatment period [ Time Frame: At baseline and at all visits during the 25-week SC Treatment Period ] [ Designated as safety issue: No ]
Change in mean Medical Research Council (MRC) sum scores during the SC treatment period [ Time Frame: At baseline and at all visits during the 25-week SC Treatment Period ] [ Designated as safety issue: No ]
Time to CIDP relapse or withdrawal due to any other reason [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
Rate of adverse events per SC infusion [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
Number of subjects with adverse events during the SC Treatment Period [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
Percentage of subjects with adverse events during the SC Treatment Period [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
Change in mean Rasch-built Overall Disability Scale (R-ODS) scores during the SC Treatment Period [ Time Frame: At baseline and at all visits during the 25-week SC Treatment Period ] [ Designated as safety issue: No ]
Time to improvement on IgPro10 Re-stabilization Therapy [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
Improvement is defined as: an INCAT score decrease by 1 point (except for the decrease from 1 to 0 in the upper limb score), R-ODS improvement by at least 4 points, or Mean Grip strength improvement by at least 8 kPa in one hand.
Change in mean grip strength during IgPro10 Re-stabilization Therapy [ Time Frame: During IgPro10 Re-stabilization Therapy, up to 12 weeks ] [ Designated as safety issue: No ]
Change in MRC sum score during IgPro10 Re-stabilization Therapy [ Time Frame: During IgPro10 Re-stabilization Therapy, up to 12 weeks ] [ Designated as safety issue: No ]
Change in R-ODS during IgPro10 Re-stabilization Therapy [ Time Frame: During IgPro10 Re-stabilization Therapy, up to 12 weeks ] [ Designated as safety issue: No ]
Change in INCAT during IgPro10 Re-stabilization Therapy [ Time Frame: During IgPro10 Re-stabilization Therapy, up to 12 weeks ] [ Designated as safety issue: No ]
Change in mean grip strength during IgPro10 Rescue Therapy [ Time Frame: During IgPro10 Rescue Therapy, up to 12 weeks ] [ Designated as safety issue: No ]
Change in MRC sum score during IgPro10 Rescue Therapy [ Time Frame: During IgPro10 Rescue Therapy, up to 12 weeks ] [ Designated as safety issue: No ]
Change in R-ODS during IgPro10 Rescue Therapy [ Time Frame: During IgPro10 Rescue Therapy, up to 12 weeks ] [ Designated as safety issue: No ]
Change in INCAT during IgPro10 Rescue Therapy [ Time Frame: During IgPro10 Rescue Therapy, up to 12 weeks ] [ Designated as safety issue: No ]
Time to improvement after CIDP relapse in the SC Treatment Period [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
Improvement is defined as a decrease in INCAT score (except for the decrease from 1 to 0 in the upper limb score) back to or below the baseline score
Time to improvement after CIDP relapse during IgPro10 Rescue Therapy [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
Improvement is defined as a decrease in INCAT score (except for the decrease from 1 to 0 in the upper limb score) back to or below the baseline score
Rate of adverse events per IgPro10 infusion [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
Number of subjects with adverse events - IgPro10 [ Time Frame: Up to 13 weeks ] [ Designated as safety issue: Yes ]
During IgPro10 Re-stabilization or Rescue Therapy
Percentage of subjects with adverse events - IgPro10 [ Time Frame: Up to 13 weeks ] [ Designated as safety issue: Yes ]
During IgPro10 Re-stabilization or Rescue Therapy


Estimated Enrollment:	350
Study Start Date:	March 2012
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: IgPro20 low dose	Biological: IgPro20 20% liquid formulation (200 mg/mL) of human normal immunoglobulin for subcutaneous use administered weekly during the SC treatment period of the study according to the randomization: 0.2 g/kg body weight (low dose arm) 0.4 g/kg body weight (high dose arm) Other Name: Hizentra Biological: IgPro10 10% Immunoglobulin G (IgG) liquid formulation of human normal immunoglobulin (Privigen®) administered intravenously during Restabilization Period of the study and/or as Rescue Therapy during SC Treatment Period for subjects with a CIDP relapse.
Experimental: IgPro20 high dose	Biological: IgPro20 20% liquid formulation (200 mg/mL) of human normal immunoglobulin for subcutaneous use administered weekly during the SC treatment period of the study according to the randomization: 0.2 g/kg body weight (low dose arm) 0.4 g/kg body weight (high dose arm) Other Name: Hizentra Biological: IgPro10 10% Immunoglobulin G (IgG) liquid formulation of human normal immunoglobulin (Privigen®) administered intravenously during Restabilization Period of the study and/or as Rescue Therapy during SC Treatment Period for subjects with a CIDP relapse.
Placebo Comparator: Placebo	Biological: Placebo 2% human albumin administered by weekly SC infusions during the SC treatment period of the study. Biological: IgPro10 10% Immunoglobulin G (IgG) liquid formulation of human normal immunoglobulin (Privigen®) administered intravenously during Restabilization Period of the study and/or as Rescue Therapy during SC Treatment Period for subjects with a CIDP relapse.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Definite or probable CIDP according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria 2010.
An IVIG treatment during the last 8 weeks prior to enrollment.
Age ≥18 years.
Written informed consent for study participation obtained before undergoing any study-specific procedures.

Exclusion Criteria:

Any polyneuropathy of other causes
Any other disease (mainly neurological or chronic orthopedic) that has caused neurological symptoms or may interfere with treatment or outcome assessments
Severe diseases and conditions that are likely to interfere with evaluation of the study product or satisfactory conduct of the study
History of thrombotic episodes within the 2 years prior to enrolment
Known allergic or other severe reactions to blood products including intolerability to previous IVIG

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01545076

Show 91 Study Locations

Sponsors and Collaborators

CSL Behring

ICON Clinical Research

Investigators


Principal Investigator:	Prof. Dr. Ivo N. van Schaik	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

More Information


Responsible Party:	CSL Behring
ClinicalTrials.gov Identifier:	NCT01545076 History of Changes
Other Study ID Numbers:	IgPro20_3003
Study First Received:	March 1, 2012
Last Updated:	September 6, 2016
Health Authority:	Australia: Human Research Ethics Committee Austria: Austrian Medicines and Medical Devices Agency Belgium: Ministry of Social Affairs, Public Health and the Environment Canada: Health Canada Czech Republic: State Institute for Drug Control Finland: Ministry of Social Affairs and Health France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Paul-Ehrlich-Institut Israel: Ministry of Health Italy: The Italian Medicines Agency Japan: Pharmaceuticals and Medical Devices Agency Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Spain: Agencia Española de Medicamentos y Productos Sanitarios United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration

Additional relevant MeSH terms:


Polyneuropathies Polyradiculoneuropathy, Chronic Inflammatory Demyelinating Polyradiculoneuropathy Peripheral Nervous System Diseases Neuromuscular Diseases Nervous System Diseases Autoimmune Diseases of the Nervous System	Demyelinating Diseases Autoimmune Diseases Immune System Diseases Immunoglobulins Antibodies Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016