Clinical trial NCT02638207: Study to Evaluate Safety and Efficacy of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly (Radiculo) Neuropathy
Official title: Prospective, Double-blind, Randomized, Multicenter Phase III Study Evaluating Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy
Keywords: Chronic Inflammatory Demyelinating Poly Neuropathy (CIDP)
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2015-12-23
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: Prospective, Double-blind, Randomized, Multicenter Phase III Study Evaluating Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy ("ProCID trial")

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

Primary outcomes:
measure: Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
timeFrame: at Week 24
Secondary outcomes:
measure: Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
timeFrame: at Week 24
measure: Grip Strength Score
timeFrame: at Week 24
measure: Inflammatory Rasch-built Overall Disability Scale (I-RODS Score)
timeFrame: at Week 24
measure: Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
timeFrame: Week 24
measure: Mean Change in Grip Strength
timeFrame: Up to 24 weeks
measure: Inflammatory Rasch-built Overall Disability Scale (I-RODS)
timeFrame: Up to 24 weeks
measure: Motor Nerves
timeFrame: Up to 24 weeks
measure: Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale)
timeFrame: Up to 24 weeks
measure: Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)
timeFrame: 24 weeks
measure: 1 Point Decrease in the INCAT Disability Score
timeFrame: 24 weeks
measure: Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Blagoevgrad
country: Bulgaria
facility: MHAT Puls EOOD
city: Sofia
country: Bulgaria
facility: St. Naum Hospital
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: Octapharma Research Site
city: Hradec Králové
country: Czechia
facility: Outpatient Clinic of Neurology
city: Pardubice
country: Czechia
facility: Regional Hospital Pardubice
city: Prague
country: Czechia
facility: Thomayer Faculty Hospital
city: Goettigen
country: Germany
facility: University Medical Center Goettigen
city: Budapest
country: Hungary
facility: Jahn Ferenc Del Pesti Korhaz
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem ÁOK Neurológiai Klinika
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Klinika Neurologii
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Specjalistyczny W Olsztynie
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny
city: Braşov
country: Romania
facility: Theo Health S.R.L.
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni
city: Constanţa
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Sf.Apostol Andrei" Constanta
city: Kazan'
country: Russian Federation
facility: Republican Clinical Neurological Centre
city: Moscow
country: Russian Federation
facility: Neurology Research Centre
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhny Novgorod Regional Clinical Hospital N.A. N.A.Semashko
city: Saint Petersburg
country: Russian Federation
facility: National Medical Research Centre of Psychiatry and Neurology n.a. V.M.Bekhterev
city: Saint Petersburg
country: Russian Federation
facility: City Multifield Hospital #2
city: Ivano-Frankivs'k
country: Ukraine
facility: Ivano Frankivsk National Medical University
city: Kyiv
country: Ukraine
facility: National Medical Academy Of Postgraduate Education Named After P.L. Shupyk
city: Luts'k
country: Ukraine
facility: Volyn Regional Clinical Hospital
city: Vinnytsia
country: Ukraine
facility: Vinnytsia National Medical University
city: Zaporizhzhya
country: Ukraine
facility: Municipal Institution Zaporizhzhya Regional Clinical Hospital
Study officials:
affiliation: Octapharma
name: Wolfgang Frenzel, MD
role: STUDY_DIRECTOR
References:
citation: Cornblath DR, van Doorn PA, Hartung HP, Merkies ISJ, Katzberg HD, Hinterberger D, Clodi E; ProCID Investigators. Randomized trial of three IVIg doses for treating chronic inflammatory demyelinating polyneuropathy. Brain. 2022 Apr 29;145(3):887-896. doi: 10.1093/brain/awab422.