Study to Evaluate Safety and Efficacy of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly (Radiculo) Neuropathy
Condition: Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy
MeSH terms: Peripheral Nervous System Diseases
Intervention: NewGam
Intervention description: In the Dose-evaluation Phase, all patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (0.5, 1.0 or 2.0 g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). If a patient is randomized to receive the low or medium NewGam dose, the same volume with the same infusion rate as would have been applied in case the patient would have been randomized to 2.0 g/kg NewGam will be used, thus supplemented with an authorized 0.9% w/v isotonic sodium chloride solution as appropriate and detailed in the following infusion bag split to maintain the blinding
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 142.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Chronic Inflammatory Demyelinating Poly Neuropathy (CIDP)

Summary:

      Study to evaluate the Efficacy and Safety of Three Different Dosages of NewGam in Patients
      With Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with diagnosis of definite or probable Chronic inflammatory demyelinating
             polyneuropathy (CIDP) according to the European Federation of Neurological
             Societies/Peripheral Nerve Society (EFNS/PNS) Guideline 2010 [van den Bergh et al.,
             2010]; including patients with Multifocal Acquired Demyelinating Sensory And Motor
             Neuropathy (MADSAM) or pure motor Chronic inflammatory demyelinating polyneuropathy
             (CIDP )

          2. Patients currently depending on treatment with immunoglobulins or corticosteroids

          3. Patients with active disease, i.e. not being in remission, who are progressive or
             relapsing prior to trial start or during the Wash-out Phase

          4. Weakness of at least 2 limbs

          5. >18 to <80 years of age

          6. Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score between
             2 and 9 (with a score of 2 coming exclusively from leg disability)

          7. Voluntarily given, fully informed written consent obtained from patient before any
             study-related procedures are conducted

        Exclusion Criteria:

          1. Unifocal forms of Chronic inflammatory demyelinating polyneuropathy (CIDP)

          2. Pure sensory Chronic inflammatory demyelinating polyneuropathy (CIDP)

          3. Multifocal motor neuropathy (MMN) with conduction block [van den Bergh et al., 2010]

          4. Patients who previously failed immunoglobulin treatment

          5. Treatment with immunomodulatory/suppressive agents (cyclosporin, methotrexate,
             mitoxantrone, mycophenolate mofetil or azathioprine) during the six months prior to
             baseline visit

          6. Patients on or treated with rituximab, alemtuzumab, cyclophosphamide, or other
             intensive chemotherapeutic regimens, previous lymphoid irradiation or stem cell
             transplantation during the 12 months prior to baseline visit

          7. Respiratory impairment requiring mechanical ventilation

          8. Myelopathy or evidence of central nervous system demyelination or significant
             persisting neurological deficits from stroke, or central nervous system (CNS) trauma

          9. Clinical evidence of peripheral neuropathy from another cause such as

               1. connective tissue disease or systemic lupus erythematosus (SLE)

               2. HIV infection, hepatitis, Lyme disease

               3. cancer (with the exception of basal cell skin cancer)

               4. IgM paraproteinemia with anti-myelin associated glycoprotein antibodies

         10. Diabetic neuropathy

         11. Cardiac insufficiency (New York Heart Association [NYHA] III/IV), cardiomyopathy,
             significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic
             heart disease

         12. Severe liver disease (ALAT 3x > normal value)

         13. Severe kidney disease (creatinine 1.5x > normal value)

         14. Hepatitis B, hepatitis C or HIV infection

         15. 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 deep vein thrombosis (DVT)

         16. Body mass index (BMI) ≥40 kg/m2

         17. Patients with uncompensated hypothyroidism (abnormally high Thyroid-Stimulating
             Hormone [TSH] and abnormally low Thyroxine [T4]) or known vitamin B12 deficiency if
             patients don't receive adequate substitution therapy

         18. Medical conditions whose symptoms and effects could alter protein catabolism and/or
             Immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic
             syndrome)

         19. Known Immunoglobulin A (IgA) deficiency with antibodies to Immunoglobulin A (IgA)

         20. History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response to
             immuno-globulin, blood or plasma derived products, or any component of NewGam

         21. Known blood hyperviscosity, or other hypercoagulable states

         22. Use of other blood or plasma-derived products within three months prior to Visit 2

         23. Patients with a past or present history of drug abuse or alcohol abuse within the
             preceding five years prior to baseline visit

         24. Patients unable or unwilling to understand or comply with the study protocol

         25. Participation in another interventional clinical study with investigational medicinal
             product (IMP) treatment currently or during the three months prior to Visit 2

         26. Women who are breast feeding, pregnant, or planning to become pregnant, or are
             unwilling to use an effective birth control method (such as implants, injectables,
             combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or
             vasectomized partner) while on study