Study to Evaluate Safety and Efficacy of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly (Radiculo) Neuropathy (CIDP)

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

Study Overview

• Status: Completed
• Conditions: Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy
• Intervention / Treatment: Drug: NewGam

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")

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • MHAT Puls EOOD
  • Sofia, Bulgaria, 1797
    • St. Naum Hospital
• Canada
  • Montréal, Canada, H3A2B4
    • Octapharma Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
• Czechia
  • Hradec Králové, Czechia, 500 03
    • Outpatient Clinic of Neurology
  • Pardubice, Czechia, 532 03
    • Regional Hospital Pardubice
  • Prague, Czechia, 140 00
    • THOMAYER Faculty Hospital
• Germany
  • Goettigen, Germany, 37075
    • University Medical Center Goettigen
• Hungary
  • Budapest, Hungary, 1204
    • Jahn Ferenc Del Pesti Korhaz
  • Szeged, Hungary, 6725
    • Szegedi Tudományegyetem ÁOK Neurológiai Klinika
• Poland
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Klinika Neurologii
  • Olsztyn, Poland, 10-561
    • Wojewódzki Szpital Specjalistyczny w Olsztynie
  • Wrocław, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny
• Romania
  • Braşov, Romania, 500091
    • Theo Health S.R.L.
  • Bucharest, Romania, 022328
    • Institutul Clinic Fundeni
  • Constanţa, Romania, 900591
    • Spitalul Clinic Judetean de Urgenta "Sf.Apostol Andrei" Constanta
• Russian Federation
  • Kazan', Russian Federation, 420021
    • Republican Clinical Neurological Centre
  • Moscow, Russian Federation, 125367
    • Neurology Research Centre
  • Nizhny Novgorod, Russian Federation, 603126
    • Nizhny Novgorod regional clinical hospital n.a. N.A.Semashko
  • Saint Petersburg, Russian Federation, 192019
    • National Medical Research Centre of Psychiatry and Neurology n.a. V.M.Bekhterev
  • Saint Petersburg, Russian Federation, 194354
    • City Multifield Hospital #2
• Ukraine
  • Ivano-Frankivs'k, Ukraine, 76008
    • Ivano Frankivsk National Medical University
  • Kyiv, Ukraine, 4112
    • National Medical Academy Of Postgraduate Education Named After P.L. Shupyk
  • Luts'k, Ukraine, 4300
    • Volyn Regional Clinical Hospital
  • Vinnytsia, Ukraine, 21005
    • Vinnytsia National Medical University
  • Zaporizhzhya, Ukraine, 69600
    • Municipal Institution Zaporizhzhya Regional Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.5 g/kg NewGam; 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 (0.5g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days).	Drug: NewGam; 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; Other Names: Panzyga
Experimental: 1.0 g/kg NewGam; 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 (1.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days).	Drug: NewGam; 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; Other Names: Panzyga
Experimental: 2.0 g/kg NewGam; 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 (2.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days).	Drug: NewGam; 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; Other Names: Panzyga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Octapharma

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2017
• Primary Completion (Actual): September 5, 2019
• Study Completion (Actual): September 5, 2019

Study Registration Dates

• First Submitted: December 16, 2015
• First Submitted That Met QC Criteria: December 18, 2015
• First Posted (Estimate): December 23, 2015

Study Record Updates

• Last Update Posted (Actual): February 16, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Chronic Inflammatory Demyelinating Poly Neuropathy (CIDP)
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: NGAM-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No