Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Treatment With Subcutaneous Immunoglobulin (IgPro20)

NCT01545076 | Completed Phase 3 Results DMC

• 1 other identifier: IgPro20_3003
• Study Type: interventional
• Target: 208
• Locations: 15 countries
• Sites: 89

Brief Summary

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.

Conditions

Chronic Inflammatory Demyelinating Polyneuropathy; Polyradiculoneuropathy

Outcome Measures

Primary Outcomes (1)

• Percentage (%) of Subjects With CIDP Relapse or Are Withdrawn for Any Other Reason During the Subcutaneous (SC) Treatment Period

  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). The INCAT score is a 10-point scale that covers the functionality of legs and arms, and has been successfully used to measure treatment effects in various CIDP studies. Scores for arm disability range from 0 ("No upper limb problems") to 5 ("Inability to use either arm for any purposeful movement"), and scores for leg disability range from 0 ("Walking not affected") to 5 ("Restricted to wheelchair, unable to stand and walk a few steps with help"). The INCAT (total) score is the sum of these 2 scores and ranges from 0 to 10. For the "adjusted" INCAT score, changes in the function of the upper limbs from 0 (normal) to 1 (minor symptoms) or from 1 to 0 were not recorded as deterioration or improvement because these changes are not considered clinically significant.

  Up to 25 weeks

Secondary Outcomes (24)

• Change in Inflammatory Neuropathy Cause and Treatment (INCAT) Scores During the SC Treatment Period

  Baseline and up to 25 weeks

• Median Change From Baseline in the Mean Grip Strength Scores of the Dominant Hand During the SC Treatment Period

  Baseline and up to 25 weeks

• Change in the Medical Research Council (MRC) Sum Scores During the SC Treatment Period

  Baseline and up to 25 weeks

• Change in Rasch-built Overall Disability Scale (R-ODS) Scores During the SC Treatment Period

  Baseline and up to 25 weeks

• Time to CIDP Relapse or Withdrawal Due to Any Other Reason During the SC Treatment Period

  Up to 25 weeks

Study Arms (3)

IgPro20 low dose

EXPERIMENTAL

Biological: IgPro20 (low dose); Biological: IgPro10

IgPro20 high dose

EXPERIMENTAL

Biological: IgPro10; Biological: IgPro20 (high dose)

Placebo

PLACEBO COMPARATOR

Biological: Placebo; Biological: IgPro10

Interventions

IgPro20 (low dose) BIOLOGICAL

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)

Also known as: Hizentra

IgPro20 low dose

Placebo BIOLOGICAL

2% human albumin administered by weekly SC infusions during the SC treatment period of the study.

Placebo

IgPro10 BIOLOGICAL

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.

IgPro20 high dose; IgPro20 low dose; Placebo

IgPro20 (high dose) BIOLOGICAL

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: 0.4 g/kg body weight (high dose arm)

Also known as: Hizentra

IgPro20 high dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• CSL Behring: lead
• ICON Clinical Research: collaborator

Study Sites (91)

Site reference 8400181

Birmingham, Alabama, 35233, United States

Location

Site reference 8400173

Phoenix, Arizona, 85013, United States

Location

Site reference 8400172

Phoenix, Arizona, 85018, United States

Location

Site reference 8400167

Los Angeles, California, 90033, United States

Location

Site reference 8400077

Centennial, Colorado, 80112, United States

Location

Site Reference 8400352

Washington D.C., District of Columbia, 20037, United States

Location

Site reference 8400214

Miami, Florida, 33136, United States

Location

Site reference 8400162

Chicago, Illinois, 60611, United States

Location

Site Reference 8400247

Chicago, Illinois, 60611, United States

Location

Site Reference 8400215

Indianapolis, Indiana, 46202, United States

Location

Site reference 8400166

Kansas City, Kansas, 66160, United States

Location

Site Reference 8400347

New Brunswick, New Jersey, 08901, United States

Location

Site reference 8400169

New York, New York, 10021, United States

Location

Site reference 8400179

New York, New York, 10021, United States

Location

Site reference 8400182

Charlotte, North Carolina, 28204, United States

Location

Site Reference 8400346

Durham, North Carolina, 27710, United States

Location

Site reference 8400178

Columbus, Ohio, 43210, United States

Location

Site reference 8400217

Oklahoma City, Oklahoma, 73104, United States

Location

Site Reference 8400177

Nashville, Tennessee, 37232, United States

Location

Site reference 8400164

Houston, Texas, 77030, United States

Location

Site Reference 8400268

Charlottesville, Virginia, 22908, United States

Location

Site Reference 8400340

Seattle, Washington, 98195, United States

Location

Site Reference 0360017

Herston, Queensland, 4029, Australia

Location

Site reference 0360011

Fitzroy, Victoria, Australia

Location

Site reference 0360008

Southport, Australia

Location

Site reference 0560003

Leuven, Belgium

Location

Site Reference 1240048

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Site Reference 1240051

Montreal, Quebec, H3A 2B4, Canada

Location

Site reference 1240006

Edmonton, Canada

Location

Site reference 1240007

Québec, Canada

Location

Site reference 1240009

Toronto, Canada

Location

Site reference 2030002

Hradec Králové, Czechia

Location

Site reference 2030009

Hradec Králové, Czechia

Location

Site reference 2030003

Prague, Czechia

Location

Site Reference 2330002

Tallinn, 10138, Estonia

Location

Site Reference 2330003

Tallinn, 10617, Estonia

Location

Site reference 2460002

Helsinki, Finland

Location

Site reference 2500024

Clermont-Ferrand, France

Location

Site reference 2500013

Marseille, France

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Site reference 2500022

Nice, France

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Site reference 2500019

Pessac, France

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Site reference 2760048

Berlin, Germany

Location

Site reference 2760069

Berlin, Germany

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Site reference 2760072

Berlin, Germany

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Site reference 2760049

Bochum, Germany

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Site reference 2760080

Cologne, Germany

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Site reference 2760075

Düsseldorf, Germany

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Site Reference 2760094

Essen, 45122, Germany

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Site reference 2760052

Essen, Germany

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Site reference 2760036

Göttingen, Germany

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Site reference 2760053

Göttingen, Germany

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Site reference 2760054

Hanover, Germany

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Site Reference 2760113

Ibbenbueren, 49477, Germany

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Site reference 2760055

Leipzig, Germany

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Site reference 2760047

Potsdam, Germany

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Site reference 2760039

Würzburg, Germany

Location

Site reference 3760005

Haifa, Israel

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Site reference 3760002

Tel Aviv, Israel

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Site reference 3800026

Chieti, Italy

Location

Site reference 3800027

Florence, Italy

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Site reference 3800028

Genova, Italy

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Site reference 3800031

Milan, Italy

Location

Site reference 3800035

Roma, Italy

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Site reference 3800036

Roma, Italy

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Site reference 3800030

Rozzano, Italy

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Site reference 3800037

Torino, Italy

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Site Reference 3920040

Aomori, 030-8553, Japan

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Site Reference 3920042

Aomori, 030-8553, Japan

Location

Site reference 3920038

Chiba, Japan

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Site reference 3920061

Kanagawa, Japan

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Site reference 3920045

Matsumoto, Japan

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Site reference 3920058

Osaka, Japan

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Site reference 3920037

Saitama, Japan

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Site reference 3920034

Tokushima, Japan

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Site Reference 3920065

Tokyo, 113-8431, Japan

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Site Reference 3920062

Tokyo, 187-8551, Japan

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Site reference 3920032

Tokyo, Japan

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Site reference 3920035

Yamaguchi, Japan

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Site reference 5280001

Amsterdam, Netherlands

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Site reference 5280005

Maastricht, Netherlands

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Site reference 5280004

Utrecht, Netherlands

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Site Reference 6160058

Gdansk, 80-803, Poland

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Site Reference 6160060

Lodz, 90-324, Poland

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Site Reference 6160055

Lublin, 20-954, Poland

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Site reference 7240010

Barcelona, Spain

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Site reference 7240011

Barcelona, Spain

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Site reference 7240013

Madrid, Spain

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Site reference 7240014

Madrid, Spain

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Site reference 7240016

Seville, Spain

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Site reference 8260019

London, United Kingdom

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Site Reference 8260032

Manchester, M6 8HD, United Kingdom

Location

Related Publications (2)

• van Schaik IN, Bril V, van Geloven N, Hartung HP, Lewis RA, Sobue G, Lawo JP, Praus M, Mielke O, Durn BL, Cornblath DR, Merkies ISJ; PATH study group. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2018 Jan;17(1):35-46. doi: 10.1016/S1474-4422(17)30378-2. Epub 2017 Nov 6.

  PMID: 29122523 DERIVED

• van Schaik IN, van Geloven N, Bril V, Hartung HP, Lewis RA, Sobue G, Lawo JP, Mielke O, Cornblath DR, Merkies IS; PATH study group. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (The PATH Study): study protocol for a randomized controlled trial. Trials. 2016 Jul 25;17(1):345. doi: 10.1186/s13063-016-1466-2.

  PMID: 27455854 DERIVED

MeSH Terms

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Polyradiculoneuropathy

Interventions

Hizentra

Condition Hierarchy (Ancestors)

Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Trial Disclosure Manager
• Organization: CSL Behring

clinicaltrials@cslbehring.com

Use email contact

Study Officials

• Prof. Dr. Ivo N. van Schaik

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2012
• First Posted: March 6, 2012
• Study Start: March 1, 2012
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: July 5, 2018
• Results First Posted: July 5, 2018

Record last verified: 2016-12

Locations

US (22); CZ (3); ES (5); CA (5); NL (3); GB (2); DE (15); FR (4); JP (12); IT (8); AU (3); FI (1); PL (3); BE (1); IL (2)