Study to evaluate efficacy of human immune globulin in patients with CIDP-chronic neuropathy.

• Register: EUCTR
• Last refreshed on: 25 March 2013
• Main ID: EUCTR2009-017805-13-BG
• Date of registration: 13/12/2010
• Prospective Registration: Yes
• Primary sponsor: Octapharma AG
• Public title: Study to evaluate efficacy of human immune globulin in patients with CIDP-chronic neuropathy.
• Scientific title: "PROSPECTIVE, PARALLEL GROUP, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMISED, MULTICENTRE, ADAPTIVE, TWO-STAGE PHASE II/III STUDY EVALUATING SAFETY AND EFFICACY OF THREE DIFFERENT DOSAGES OF NEWGAM IN PATIENTS WITH CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY (POINT TRIAL)” - NGAM-03
• Date of first enrolment: 27/01/2011
• Target sample size: 172
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017805-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: three dosage forms Number of treatment arms in the trial: 4

Countries of recruitment

Bulgaria, Czech Republic, India, Mexico, Poland, Romania, Serbia, Ukraine

Contacts

• Name: Clinical Research Department
• Affiliation: Octapharma Pharmazeutika Produktionsgesellschaft mbH

• Name: Clinical Research Department
• Affiliation: Octapharma Pharmazeutika Produktionsgesellschaft mbH

Key inclusion & exclusion criteria

Inclusion criteria:
•Patients diagnosed as having CIDP by a neurologist experienced in neuromuscular diseases based on fulfilment of clinical criteria of the INCAT Group and the definite electrophysiological criteria for CIDP of the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS); patients with Multifocal Acquired Demyelinating Sensory And Motor neuropathy (MADSAM) or pure motor CIDP will be included provided they fulfil these criteria
• Worsening of disability and objective increase in weakness or sensory deficit during the 6 months prior to screening
• = 18 years of age
• Overall adjusted INCAT disability score between 2-9 (see Appendix 1); a score of 2 has to result exclusively from leg disability
• Expanded Medical Research Council (MRC) sum score of = 74 (see Appendix 2)
• Freely given written informed consent from patient
• Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study
• Women of reproductive age: negative result of pregnancy test (human chorionic gonadotropin [HCG]-based assay in urine) and surgically sterile, sexually inactive, or willing to use adequate contraception for the duration of the trial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion criteria:
•Unifocal forms of CIDP
•Pure sensory CIDP
•Multifocal motor neuropathy (MMN) with conduction block, defined as a lower motor neuron disorder with motor weakness in an upper limb, without sensory deficit and with proximal conduction block (50% decrease in amplitude/area with proximal compared with distal stimulation) in motor nerves and normal sensory nerve conduction studies (NCS)
•Treatment of CIDP with immunoglobulins (intravenous or subcutaneous) at any time prior to study entry
•Steroids of any type equivalent to prednisolone or prednisone > 10 mg/day or equivalent, e.g., > 20 mg every 2 days or plasma exchange (PE) during the last 3 months prior to baseline visit
•Treatment with azathioprine during 12 months prior to baseline visit unless on a stable dose throughout at least 12 months prior to baseline. Patients who are on a stable dose for at least 12 months prior to baseline should be expected to continue taking the same dose during the trial.
•Treatment with cyclosporin, methotrexate, mitoxantrone, mycophenolate mofetil, interferon or other immunosuppressive or immunomodulatory drugs during the three months prior to baseline visit
•Patients ever treated with rituximab, alemtuzumab, cyclophosphamide, or other intensive chemotherapeutic regimens, previous lymphoid irradiation or stem cell transplantation
•Respiratory impairment requiring mechanical ventilation
•Myelopathy or clinical evidence of central nervous system (CNS) demyelination, trauma or stroke
•Clinical evidence of peripheral neuropathy from another cause such as
-connective tissue disease or systemic lupus erythematosus,
-HIV infection, hepatitis, Lyme disease,
-cancer (with the exception of benign skin cancer), lymphoma, malignant plasma cell dyscrasia, Castleman’s disease
-IgM paraproteinaemia with anti-myelin associated glycoprotein antibodies
•Known diabetes mellitus
•Other serious medical condition complicating assessment or treatment including but not limited to
ocardiac insufficiency (New York Heart Association [NYHA] III/IV), known cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease,
osevere liver disease (ALAT > 3x upper limit of normal for the testing laboratory),
osevere kidney disease (creatinine > 120 µM),
ohepatitis B or C or HIV infection
•Thromboembolic events: patients with a history of deep vein thrombosis (DVT) within the last year prior to baseline visit or pulmonary embolism ever; patients with susceptibility to embolism or DVT
•Patients with known uncompensated hypothyroidism (abnormally high Thyroid-Stimulating Hormone (TSH), and abnormally low thyroxine (T4)) or known vitamin B12 deficiency
•Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilisation (e.g. protein-losing enteropathies, nephrotic syndrome)
•Known IgA deficiency with antibodies to IgA
•History of hypersensitivity, anaphylaxis or severe systemic response to immunoglobulin, blood or plasma derived products, or any component of NewGam
•Known blood hyperviscosity, or other hypercoagulable states
•Operation within 3 months prior to baseline visit in which blood products have been used
•Patients with a past or present history of drug or alcohol abuse
•Patients unable or unwilling to understand or comply with the study protocol
•Patients with any condition that would make the patient, in the opinion of the Investigator, unsuitable for the study
•Liv

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
MedDRA version: 14.0 Level: PT Classification code 10057645 Term: Chronic inflammatory demyelinating polyradiculoneuropathy System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: NewGam
Product Code: NewGam
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Immunoglobuline G
Other descriptive name: NewGam
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 86-110
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: Stage 1 (Phase 2 dose-finding part):
• Determination and selection (after a loading dose of 2.0 g/kg NewGam) of one dosage from three NewGam maintenance dosage arms (0.4 g/kg or 1.0 g/kg or 2.0 g/kg given every 21 [±4] days starting at Week 3) in comparison with a placebo arm, based on the percentage of responders (response defined as a decrease, meaning improvement, in the adjusted INCAT disability score by at least 1 point) at Week 24. The selected NewGam dosage and placebo will be employed and compared in Stage 2.

Stage 2 (Phase 3 confirmatory part):
• To demonstrate superiority (after a loading dose of 2.0 g/kg NewGam) of the maintenance dosage regimen selected at study Stage 1 (out of 0.4 g/kg, 1.0 g/kg or 2.0 g/kg NewGam) over placebo in patients with CIDP as assessed by the percentage of responders (response defined as a decrease, meaning improvement, in the adjusted INCAT disability score by at least 1 point) at Week 24.

Timepoint(s) of evaluation of this end point: Primary end point Efficacy: Response at Week 24 or at time of rescue NewGam infusion

Secondary Objective: To evaluate the safety and efficacy of NewGam administration in patients with
CIDP through other parameters (see Section 3.1.2) at Week 24 (or time of rescue infusion) compared to baseline.

Primary end point(s): Efficacy:
Response at 24 weeks or at time of rescue NewGam infusion using the adjusted INCAT disability score. Response is defined as a decrease relative to baseline of at least 1 point on the adjusted INCAT disability score, a scale from 0 to 10 (from healthy to unable to make any purposeful movements with arms or legs in which the change from 0 to 1 in the upper limb component is discounted, see Appendix 1)
The results from the Stage 1 (dose-finding phase II part) of this seamless phase II/III trial will be used to adopt the sample size in the Stage 2 (efficacy phase III part), and also to only continue - in addition to the placebo arm - with the NewGam arm that is the most efficacious as shown by IA.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: A. Endpoint Efficacy :Mean change from baseline at Week 24 or at time of rescue NewGam infusion
B.Endpoints safety: Occurrence of all AEs throughout entire 48-weeks (36-weeks in Stage 2); laboratory parameters throughout entire 48-weeks (36-weeks in Stage 2), neurological examination throughout entire 48-weeks (36-weeks in Stage 2).

Secondary end point(s): Efficacy:
• Mean change from baseline at Week 24 or at time of rescue NewGam infusion in :
- grip strength of dominant hand or if ambidextrous right hand
- adjusted INCAT disability score
- the sum of the distal-evoked amplitude of 4 right sided motor nerves
- expanded MRC sum score
• Time to 1 point increase in adjusted INCAT disability score to or above baseline value after temporary 1 or more point decrease

Safety:
- Occurrence of all AEs throughout entire 48-week trial period starting with the first infusion
- Short term tolerance parameters including vital signs throughout entire 48-week trial period
- Standard ECG (at screening and termination visit)
- Physical/neurological examination at 12-week intervals throughout entire 48-week trial period
- Laboratory parameters throughout entire 48-week trial period (except baseline and Week 15, 21, 30 and 42 in Stage 1)
- Tests for viral safety (at screening and termination visit)

Secondary ID(s)

2009-017805-13-CZ

NGAM-03

Source(s) of Monetary Support

Octapharma AG