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

• ClinicalTrials.gov Identifier: NCT02638207
• Recruitment Status: Completed
• First Posted: December 23, 2015
• Results First Posted: February 16, 2021
• Last Update Posted: February 16, 2021
• Sponsor: Octapharma
• Information provided by (Responsible Party): Octapharma

Tracking Information

• First Submitted Date: December 16, 2015
• First Posted Date: December 23, 2015
• Results First Submitted Date: September 3, 2020
• Results First Posted Date: February 16, 2021
• Last Update Posted Date: February 16, 2021
• Actual Study Start Date: September 27, 2017
• Actual Primary Completion Date: September 5, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 3, 2020)

Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score [ Time Frame: at Week 24 ]

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)

Original Primary Outcome Measures (submitted: December 18, 2015)

Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score [ Time Frame: at Week 24 ]

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)

Current Secondary Outcome Measures (submitted: November 20, 2020)

• Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score [ Time Frame: at Week 24 ]
  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
• Grip Strength Score [ Time Frame: at Week 24 ]
  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)
• Inflammatory Rasch-built Overall Disability Scale (I-RODS Score) [ Time Frame: at Week 24 ]
  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
• Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score [ Time Frame: Week 24 ]
  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)
• Mean Change in Grip Strength [ Time Frame: Up to 24 weeks ]
  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.
• Inflammatory Rasch-built Overall Disability Scale (I-RODS) [ Time Frame: Up to 24 weeks ]
  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.
• Motor Nerves [ Time Frame: Up to 24 weeks ]
  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.
• Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale) [ Time Frame: Up to 24 weeks ]
  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.
• Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) [ Time Frame: 24 weeks ]
  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).
• 1 Point Decrease in the INCAT Disability Score [ Time Frame: 24 weeks ]
  Time to 1 point decrease (improvement of disability) in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score
• Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) [ Time Frame: 24 weeks ]
  Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS) scores

Original Secondary Outcome Measures (submitted: December 18, 2015)

• Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score [ Time Frame: at Week 24 ]
  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
• Grip Strength Score [ Time Frame: at Week 24 ]
  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)
• Inflammatory Rasch-built overall disability scale (I-RODS Score) [ Time Frame: at Week 24 ]
  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
• Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score [ Time Frame: through study completion, an average of 2 years ]
  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)
• Mean Change in grip strength [ Time Frame: through study completion, an average of 2 years ]
  Mean change from baseline (Week 0) to Termination Visit in grip strength of dominant hand (assessed by Martin vigorimeter) or if ambidextrous right hand
• Inflammatory Rasch-built overall disability scale (I-RODS) [ Time Frame: through study completion, an average of 2 years ]
  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; Appendix 1) and number of improvers
• Right sided motor nerves [ Time Frame: through study completion, an average of 2 years ]
  Mean change from baseline (Week 0) to Termination Visit in sum of the distal evoked amplitude of 4 right sided motor nerves (peroneal, tibial, ulnar and median)
• Mean Change in pain intensity numerical rating scale (PI-NRS Scale) [ Time Frame: through study completion, an average of 2 years ]
  Mean change from baseline (Week 0) to Termination Visit in Pain Intensity Numeric Rating Scale (PI-NRS)
• Worsening on the Inflammatory Rasch-built overall disability scale (I-RODS Scale) [ Time Frame: through study completion, an average of 2 years ]
  Time to first confirmed worsening on the I-RODS scale
• 1 point decrease in the INCAT disability score [ Time Frame: through study completion, an average of 2 years ]
  Time to 1 point decrease (improvement of disability) in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score
• decrease in Inflammatory Rasch-built overall disability scale (I-RODS Scale) [ Time Frame: through study completion, an average of 2 years ]
  Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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")
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy

Intervention

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 Name: Panzyga

Study Arms

• 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).
  Intervention: Drug: NewGam
• 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).
  Intervention: Drug: NewGam
• 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).
  Intervention: Drug: NewGam

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 24, 2019): 142
• Original Estimated Enrollment (submitted: December 18, 2015): 140
• Actual Study Completion Date: September 5, 2019
• Actual Primary Completion Date: September 5, 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Canada, Czechia, Germany, Hungary, Poland, Romania, Russian Federation, Ukraine
• Removed Location Countries: Australia, Denmark, Sweden

Administrative Information

• NCT Number: NCT02638207
• Other Study ID Numbers: NGAM-08
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Octapharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Octapharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Wolfgang Frenzel, MD; Octapharma

• PRS Account: Octapharma
• Verification Date: January 2021