Study of Efficacy and Safety of Privigen in Subjects With Chronic Inflammatory Demyelinating Polyneuropathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01184846
First received: August 18, 2010
Last updated: August 27, 2013
Last verified: March 2013
  Purpose

The objective of this study is to demonstrate the efficacy and safety of Privigen in subjects with CIDP.


Condition Intervention Phase
Chronic Inflammatory Demyelinating Polyneuropathy
Biological: 10% liquid formulation of human immunoglobulin
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-arm Study to Demonstrate the Efficacy and Safety of Privigen in the Treatment of Subjects With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Responder Rate [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]

    Percentage of responders based on the adjusted Inflammatory Neuropathy Cause and Treatment Scale (INCAT) score.

    Responders were defined as those subjects who: 1) demonstrated a "clinically meaningful improvement" between baseline and Week 25, or 2) who were discontinued from the study for any reason after the start of IgPro10 treatment but with "clinically meaningful improvement" at the last study visit.

    "Clinically meaningful improvement" was a decrease of at least 1 adjusted INCAT score point excluding an improvement of one point in the total score if this improvement was only due to a decrease in the upper limb score of 1 to 0.



Secondary Outcome Measures:
  • Change in Adjusted INCAT Score [ Time Frame: Up to 34 weeks ] [ Designated as safety issue: No ]

    The change in INCAT score was determined at the completion visit compared to baseline and to the last measurement under the previous IVIG treatment using a non-parametric analysis to calculate the Hodges-Lehmann point estimate and the corresponding Tukey confidence interval on an exploratory basis.

    The INCAT disability score ranges from 0 to 10 and is the sum of arm and leg disability each rated between 0 and 5 (where arm = 0 indicates 'no upper limb problems' and arm = 5 indicates 'inability to use either arm for any purposeful movement', and leg = 0 indicates 'walking not affected', and leg = 5 indicates 'restricted to wheelchair, unable to stand and walk a few steps with help'). Thus, a higher INCAT disability score indicates greater disability. Negative values for change in INCAT score indicate improvement, with a more negative value indicating greater improvement compared with the value at baseline.


  • Change in Maximum Grip Strength [ Time Frame: Up to 34 weeks ] [ Designated as safety issue: No ]
    Change in maximum grip strength of the dominant hand. A non-parametric analysis was used to calculate the Hodges-Lehmann point estimate and the corresponding Tukey confidence interval on an exploratory basis. Positive values for change in maximum grip strength indicate improvement.

  • Change in Medical Research Council Sum Scale (MRC) [ Time Frame: Up to 34 weeks ] [ Designated as safety issue: No ]

    The change in MRC sum score was determined at the completion visit compared to baseline and to the last measurement under the previous IVIG treatment using a non-parametric analysis to calculate the Hodges-Lehmann point estimate and the corresponding Tukey confidence interval on an exploratory basis.

    The 80-point MRC sum score is the sum of scores for eight bilateral (left and right side) muscle groups, each rated between 0 (no visible contraction) to 5 (normal movement). A higher MRC sum score indicates greater muscle contraction/limb movement. Positive values for change in MRC sum score indicate improvement, with a more positive value indicating greater muscle contraction/ limb movement compared with the value at baseline.


  • Immunoglobulin G (IgG) Level [ Time Frame: At baseline and at Weeks 7, 13 and 19 (levels determined immediately before and after IVIG infusion), and at completion visit (Week 25) ] [ Designated as safety issue: No ]
  • Frequency of Adverse Events (AEs) [ Time Frame: For the duration of the study, up to 34 weeks ] [ Designated as safety issue: Yes ]
    Overall rate of AEs per infusion.

  • Severity of AEs Per Infusion [ Time Frame: For the duration of the study, up to 34 weeks ] [ Designated as safety issue: Yes ]

    The severity of each AE was to be graded by the investigator as follows:

    • Mild: Symptoms were easily tolerated and there was no interference with daily activities.
    • Moderate: Discomfort enough to cause some interference with daily activities.
    • Severe: Incapacitating with inability to work or do usual activity.

  • Severity of AEs Per Subject [ Time Frame: 34 weeks ] [ Designated as safety issue: Yes ]

    The severity of each AE was to be graded by the investigator as follows:

    • Mild: Symptoms were easily tolerated and there was no interference with daily activities.
    • Moderate: Discomfort enough to cause some interference with daily activities.
    • Severe: Incapacitating with inability to work or do usual activity.

  • Relatedness of AEs Per Infusion [ Time Frame: For the duration of the study, up to 34 weeks ] [ Designated as safety issue: Yes ]
    The causal relationship of an AE to the study drug was to be assessed and assigned by the investigator.

  • Relatedness of AEs Per Subject [ Time Frame: For the duration of the study, up to 34 weeks ] [ Designated as safety issue: Yes ]
    The causal relationship of an AE to the study drug was to be assessed and assigned by the investigator.

  • Mean Change in Systolic and Diastolic Blood Pressure During Infusion [ Time Frame: At Days 1 to 5 and at Weeks 4, 7, 10, 13, 16, 19 and 22. ] [ Designated as safety issue: No ]
    Systolic and diastolic blood pressure (BP) were measured before the start of IgPro10 infusion, at 30 minutes and 1 hour after the start of infusion, then every hour until the end of infusion and at 1 hour after the end of infusion. Mean changes from the pre-infusion value to each of the post-infusion values were calculated for each infusion, and the mean value and standard deviation (SD) of these individual mean changes is reported.

  • Mean Change in Pulse Rate During Infusion [ Time Frame: At Days 1 to 5 and at Weeks 4, 7, 10, 13, 16, 19 and 22. ] [ Designated as safety issue: No ]
    Pulse rate was measured before the start of IgPro10 infusion, at 30 minutes and 1 hour after the start of infusion, then every hour until the end of infusion and at 1 hour after the end of infusion. Mean changes from the pre-infusion value to each of the post-infusion values were calculated for each infusion, and the mean value and SD of these individual mean changes is reported.

  • Mean Change in Body Temperature During Infusion [ Time Frame: At Days 1 to 5 and at Weeks 4, 7, 10, 13, 16, 19 and 22. ] [ Designated as safety issue: No ]
    Body temperature was measured before the start of IgPro10 infusion, at 30 minutes and 1 hour after the start of infusion, then every hour until the end of infusion and at 1 hour after the end of infusion. Mean changes from the pre-infusion value to each of the post-infusion values were calculated for each infusion, and the mean value and SD of these individual mean changes is reported.

  • Number of Subjects With Normal/Abnormal Not Clinically Significant (ANCS) Value at Baseline Changing to Abnormal Clinically Significant (ACS) Value at Completion Visit in Routine Laboratory Parameters. [ Time Frame: At Day 1 (baseline) and at Completion Visit (Week 25 or early discontinuation) ] [ Designated as safety issue: No ]
    Number of subjects with changes from normal/ANCS values at baseline to ACS values at Completion Visit in routine laboratory parameters including hematology and serum chemistry analytes. Investigators flagged each laboratory value as normal, ANCS or ACS at each assessment timepoint.


Enrollment: 31
Study Start Date: November 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IgPro10
10% liquid formulation of human immunoglobulin (IgPro10). IgPro10 will be administered by IV infusion as one induction dose of 2 g/kg body weight (bw), followed by seven 3-weekly maintenance doses of 1 g/kg bw.
Biological: 10% liquid formulation of human immunoglobulin
Other Name: IgPro10; Privigen

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

IVIG-untreated subjects:

  • Either subjects with newly diagnosed CIDP (developing over at least 2 months) or subjects with an IVIG treatment interruption for at least 1 year with a progressive disease (deteriorating in the last 2 months) prior to enrolment.
  • Actual diagnosis (including electrophysiology) of CIDP with progressive or relapsing dysfunction from motor and sensory or symmetric motor nerve only in at least 1 limb resulting from neuropathy. Criteria for definite or probable CIDP according to EFNS/PNS guideline.
  • Age ≥18 years.
  • Male or female.
  • Written informed consent for study participation obtained before undergoing any study specific procedures.

IVIG-pretreated subjects:

  • Being treated regularly with IVIG on a fixed cycle length of 2 to 6 weeks ± 5 days in the last 6 months, on a fixed dosage of ± 20 % in the last 6 months and deteriorating by at least 1 INCAT score point during the Washout Period of up to 10 weeks (except for an increase from 0 to 1 solely due to upper limb score).
  • Historic diagnosis of CIDP with progressive or relapsing dysfunction from motor and sensory or symmetric motor nerve only in at least 1 limb resulting from neuropathy. Criteria for definite or probable CIDP according to EFNS/PNS guideline.
  • Age ≥18 years.
  • Male or female.
  • Written informed consent for study participation obtained before undergoing any study specific procedures.

Exclusion Criteria:

  • A motor syndrome that fulfils criteria for multifocal motor neuropathy (MMN) with conduction block (i.e., upper limb motor weakness without sensory deficit and with a 50% decrease in action potential amplitude or area on proximal compared with distal stimulation in motor nerves).
  • CIDP with monoclonal gammopathy of uncertain significance (CIDP-MGUS) with anti-MGUS antibodies and patients with distal acquired demyelinating symmetric (DADS)neuropathy.
  • Any disease (mainly neurological or chronic orthopedic) that may cause symptoms or may interfere with treatment or outcome assessments with the INCAT (e.g., diphtheria, drug or toxin exposure and diabetes mellitus likely to have caused the neuropathy, IgM paraproteinemia, familial neuropathy, borreliosis with radiculopathy, post-polio-syndrome,M. Parkinson, stroke).
  • Current malignancy.
  • History of cardiac insufficiency (New York Heart Association [NYHA] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, congestive heart failure or severe hypertension.
  • History of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident).
  • Migraine associated with IVIG infusion in the last 3 months prior to enrolment.
  • Known allergic or other severe reactions to blood products including intolerability to previous IVIG (i.e. severe headache, hypersensitivity, intravascular hemolysis).
  • Subjects with serum IgA level less than 50% of the lower normal limit.
  • Known hyperprolinemia.
  • Any condition (including alcohol, drug or medication abuse) that is likely to interfere with evaluation of the study product or satisfactory conduct of the study.
  • Plasma exchange 3 months prior to enrolment.
  • Treatment with immunomodulatory agents others than steroids, methotrexate or azathioprine (e.g. interferon, TNF-α inhibitors) within 6 months before enrolment.
  • Treatment with rituximab in the 12 months before enrolment.
  • Abnormal laboratory parameters: creatinine > 1.5 times the upper normal limit (UNL), lactate dehydrogenase (LDH) > 1.5 times the UNL, C-reactive protein (CRP) > 1.5 times the UNL, hemoglobin (Hb) < 10 g/dL.
  • Ongoing HIV, hepatitis C and hepatitis B infection.
  • Participation in another clinical study (or use of another investigational medicinal product [IMP]) within 3 months prior to enrolment
  • Not able to comply with study procedures and treatment regimen.
  • Employee at the study site, or spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse).
  • Pregnancy or nursing mother.
  • Intention to become pregnant during the course of the study.
  • Female subjects of childbearing potential either not using, or not willing to use, a medically reliable method of contraception for the entire duration of the study, or not sexually abstinent for the entire duration of the study, or not surgically sterile.
  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: NCT01184846

Locations
Belgium
Study Site
Bruxelles, Belgium
Study Site
Edegem, Belgium
Study Site
Gent, Belgium
Study Site
Leuven, Belgium
Finland
Study Site
Helsinki, Finland
Study Site
Turku, Finland
Study Site
Vaasa, Finland
France
Study Site
Limoges, France
Study Site
Lyon, France
Study Site
Marseille, France
Study Site
Montpellier, France
Study Site
Paris, France
Germany
Study Site
Berlin, Germany
Study Site
Feldberger Seenlandschaft, Germany
Study Site
Göttingen, Germany
Study Site
Itzehoe, Germany
Study Site
Prien, Germany
Study Site
Schwedt, Germany
Study Site
Würzburg, Germany
Poland
Study Site
Krakow, Poland
Study Site
Lublin, Poland
Study Site
Wroclaw, Poland
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Program Director Clinical R&D CSL Behring
  More Information

Additional Information:
Publications:
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01184846     History of Changes
Other Study ID Numbers: IgPro10_3001, 1504, 2009-017672-24
Study First Received: August 18, 2010
Results First Received: January 30, 2013
Last Updated: August 27, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by CSL Behring:
Chronic inflammatory demyelinating polyneuropathy
CIDP

Additional relevant MeSH terms:
Polyneuropathies
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Polyradiculoneuropathy
Autoimmune Diseases of the Nervous System
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Immunoglobulins
Antibodies
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014