Clinical trial NCT01184846: Study of Efficacy and Safety of Privigen in Subjects With Chronic Inflammatory Demyelinating Polyneuropathy
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Inflammatory Demyelinating Polyneuropathy
Keywords: Chronic inflammatory demyelinating polyneuropathy
CIDP
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2010-08-19
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Responder Rate
timeFrame: 25 weeks
Secondary outcomes:
measure: Change in Adjusted INCAT Score
timeFrame: Up to 34 weeks
measure: Change in Maximum Grip Strength
timeFrame: Up to 34 weeks
measure: Change in Medical Research Council Sum Scale (MRC)
timeFrame: Up to 34 weeks
measure: Immunoglobulin G (IgG) Level
timeFrame: At baseline and at Weeks 7, 13 and 19 (levels determined immediately before and after IVIG infusion), and at completion visit (Week 25)
measure: Frequency of Adverse Events (AEs)
timeFrame: For the duration of the study, up to 34 weeks
measure: Severity of AEs Per Infusion
timeFrame: For the duration of the study, up to 34 weeks
measure: Severity of AEs Per Subject
timeFrame: 34 weeks
measure: Relatedness of AEs Per Infusion
timeFrame: For the duration of the study, up to 34 weeks
measure: Relatedness of AEs Per Subject
timeFrame: For the duration of the study, up to 34 weeks
measure: Mean Change in Systolic and Diastolic Blood Pressure During Infusion
timeFrame: At Days 1 to 5 and at Weeks 4, 7, 10, 13, 16, 19 and 22.
measure: Mean Change in Pulse Rate During Infusion
timeFrame: At Days 1 to 5 and at Weeks 4, 7, 10, 13, 16, 19 and 22.
measure: Mean Change in Body Temperature During Infusion
timeFrame: At Days 1 to 5 and at Weeks 4, 7, 10, 13, 16, 19 and 22.
measure: 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.
timeFrame: At Day 1 (baseline) and at Completion Visit (Week 25 or early discontinuation)
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Study Site
city: Edegem
country: Belgium
facility: Study Site
city: Gent
country: Belgium
facility: Study Site
city: Leuven
country: Belgium
facility: Study Site
city: Helsinki
country: Finland
facility: Study Site
city: Turku
country: Finland
facility: Study Site
city: Vaasa
country: Finland
facility: Study Site
city: Limoges
country: France
facility: Study Site
city: Lyon
country: France
facility: Study Site
city: Marseille
country: France
facility: Study Site
city: Montpellier
country: France
facility: Study Site
city: Paris
country: France
facility: Study Site
city: Berlin
country: Germany
facility: Study Site
city: Feldberger Seenlandschaft
country: Germany
facility: Study Site
city: Göttingen
country: Germany
facility: Study Site
city: Itzehoe
country: Germany
facility: Study Site
city: Prien
country: Germany
facility: Study Site
city: Schwedt
country: Germany
facility: Study Site
city: Würzburg
country: Germany
facility: Study Site
city: Krakow
country: Poland
facility: Study Site
city: Lublin
country: Poland
facility: Study Site
city: Wroclaw
country: Poland
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Program Director Clinical R&D
role: STUDY_DIRECTOR
References:
citation: Leger JM, De Bleecker JL, Sommer C, Robberecht W, Saarela M, Kamienowski J, Stelmasiak Z, Mielke O, Tackenberg B, Shebl A, Bauhofer A, Zenker O, Merkies IS; PRIMA study investigators. Efficacy and safety of Privigen((R)) in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective, single-arm, open-label Phase III study (the PRIMA study). J Peripher Nerv Syst. 2013 Jun;18(2):130-40. doi: 10.1111/jns5.12017.
citation: Merkies ISJ, Lawo JP, Edelman JM, De Bleecker JL, Sommer C, Robberecht W, Saarela M, Kamienowski J, Stelmasiak Z, Mielke O, Tackenberg B, Leger JM; PRIMA trial investigators. Minimum clinically important difference analysis confirms the efficacy of IgPro10 in CIDP: the PRIMA trial. J Peripher Nerv Syst. 2017 Jun;22(2):149-152. doi: 10.1111/jns.12204. No abstract available.