Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy Clinical Trial
— CIDPOfficial 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
| Verified date | January 2021 |
| Source | Octapharma |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Study to evaluate the Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy
| Status | Completed |
| Enrollment | 142 |
| Est. completion date | September 5, 2019 |
| Est. primary completion date | September 5, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 80 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Bulgaria | MHAT Puls EOOD | Blagoevgrad | |
| Bulgaria | St. Naum Hospital | Sofia | |
| Canada | Octapharma Research Site | Montréal | |
| Canada | Toronto General Hospital | Toronto | Ontario |
| Czechia | Outpatient Clinic of Neurology | Hradec Králové | |
| Czechia | Regional Hospital Pardubice | Pardubice | |
| Czechia | Thomayer Faculty Hospital | Prague | |
| Germany | University Medical Center Goettigen | Goettigen | |
| Hungary | Jahn Ferenc Del Pesti Korhaz | Budapest | |
| Hungary | Szegedi Tudományegyetem ÁOK Neurológiai Klinika | Szeged | |
| Poland | Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Klinika Neurologii | Lublin | |
| Poland | Wojewodzki Szpital Specjalistyczny W Olsztynie | Olsztyn | |
| Poland | Uniwersytecki Szpital Kliniczny | Wroclaw | |
| Romania | Theo Health S.R.L. | Brasov | |
| Romania | Institutul Clinic Fundeni | Bucharest | |
| Romania | Spitalul Clinic Judetean de Urgenta "Sf.Apostol Andrei" Constanta | Constanta | |
| Russian Federation | Republican Clinical Neurological Centre | Kazan' | |
| Russian Federation | Neurology Research Centre | Moscow | |
| Russian Federation | Nizhny Novgorod Regional Clinical Hospital N.A. N.A.Semashko | Nizhny Novgorod | |
| Russian Federation | City Multifield Hospital #2 | Saint Petersburg | |
| Russian Federation | National Medical Research Centre of Psychiatry and Neurology n.a. V.M.Bekhterev | Saint Petersburg | |
| Ukraine | Ivano Frankivsk National Medical University | Ivano-Frankivs'k | |
| Ukraine | National Medical Academy Of Postgraduate Education Named After P.L. Shupyk | Kyiv | |
| Ukraine | Volyn Regional Clinical Hospital | Luts'k | |
| Ukraine | Vinnytsia National Medical University | Vinnytsia | |
| Ukraine | Municipal Institution Zaporizhzhya Regional Clinical Hospital | Zaporizhzhya |
| Lead Sponsor | Collaborator |
|---|---|
| Octapharma |
Bulgaria, Canada, Czechia, Germany, Hungary, Poland, Romania, Russian Federation, Ukraine,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | Efficacy - Proportion of responders in the 1.0 g/kg NewGam arm at Week 24 (Termination Visit) relative to baseline (Week 0). A responder being defined as a patient with a decrease of at least 1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (a scale from 0 to 10, from healthy to unable to make any purposeful movements with arms and/or legs) | at Week 24 | |
| Secondary | Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline compared to the 1.0 g/kg arm, based on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score | at Week 24 | |
| Secondary | Grip Strength Score | Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline at Week 0 compared to the 1.0 g/kg arm, based on the grip strength (Martin Vigorimeter) using the previously published minimum clinically important difference (MCID) cut-off of 8 kilopascal (kPa) | at Week 24 | |
| Secondary | Inflammatory Rasch-built Overall Disability Scale (I-RODS Score) | Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline at Week 0 compared to the 1.0 g/kg arm, based on the Inflammatory Rasch-built overall disability scale (I-RODS Score) using the MCID concept related to the varying standard errors (MCID-SE) as recently demonstrated | at Week 24 | |
| Secondary | Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | Time to first confirmed worsening on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale by at least 1 point from the value at baseline (Week 0) | Week 24 | |
| Secondary | Mean Change in Grip Strength | Mean change from baseline (Week 0) to Termination Visit in grip strength of both hands (assessed by Martin vigorimeter). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. | Up to 24 weeks | |
| Secondary | Inflammatory Rasch-built Overall Disability Scale (I-RODS) | Mean change from baseline (Week 0) to Termination Visit in Inflammatory Rasch-built overall disability sum score (I-RODS using the concept of MCID-SE as recently reported) and number of improvers. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
A scale from 0 to 48, from "Not possible to perform" to "Possible without any difficulty". Higher values represent a better outcome. |
Up to 24 weeks | |
| Secondary | Motor Nerves | Mean change from baseline (Week 0) to Termination Visit in sum of the distal evoked amplitude of 4 right sided and 4 left sided motor nerves (peroneal, tibial, ulnar and median). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. | Up to 24 weeks | |
| Secondary | Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale) | Mean change from baseline (Week 0) to Termination Visit in Pain Intensity Numeric Rating Scale (PI-NRS). The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
The Pain Intensity Numeric Rating Scale (PI-NRS, a numeric scale where 0 = no pain and 10 = worst possible pain) is an 11-point scale for patient self-reporting of pain. A higher value represents a worse outcome. |
Up to 24 weeks | |
| Secondary | Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | Time to first confirmed worsening on the I-RODS scale. The reported change was calculated from two time points as the value at the later time point minus the value at the earlier time point. A scale from 0 to 48, from "Not possible to perform" to "Possible without any difficulty". Higher values represent a better outcome.
Worsening is determined using the concept of MCID (minimum clinically important difference) using the individually obtained standard errors (MCID-SE). |
24 weeks | |
| Secondary | 1 Point Decrease in the INCAT Disability Score | Time to 1 point decrease (improvement of disability) in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score | 24 weeks | |
| Secondary | Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS) scores | 24 weeks |