Back to results

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

Primary Purpose

Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

NewGam

About this trial

This is an interventional treatment trial for Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy focused on measuring Chronic Inflammatory Demyelinating Poly Neuropathy (CIDP)

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 )
Patients currently depending on treatment with immunoglobulins or corticosteroids
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
Weakness of at least 2 limbs
>18 to <80 years of age
Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score between 2 and 9 (with a score of 2 coming exclusively from leg disability)
Voluntarily given, fully informed written consent obtained from patient before any study-related procedures are conducted

Exclusion Criteria:

Unifocal forms of Chronic inflammatory demyelinating polyneuropathy (CIDP)
Pure sensory Chronic inflammatory demyelinating polyneuropathy (CIDP)
Multifocal motor neuropathy (MMN) with conduction block [van den Bergh et al., 2010]
Patients who previously failed immunoglobulin treatment
Treatment with immunomodulatory/suppressive agents (cyclosporin, methotrexate, mitoxantrone, mycophenolate mofetil or azathioprine) during the six months prior to baseline visit
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
Respiratory impairment requiring mechanical ventilation
Myelopathy or evidence of central nervous system demyelination or significant persisting neurological deficits from stroke, or central nervous system (CNS) trauma
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
Diabetic neuropathy
Cardiac insufficiency (New York Heart Association [NYHA] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease
Severe liver disease (ALAT 3x > normal value)
Severe kidney disease (creatinine 1.5x > normal value)
Hepatitis B, hepatitis C or HIV infection
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)
Body mass index (BMI) ≥40 kg/m2
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
Medical conditions whose symptoms and effects could alter protein catabolism and/or Immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome)
Known Immunoglobulin A (IgA) deficiency with antibodies to Immunoglobulin A (IgA)
History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of NewGam
Known blood hyperviscosity, or other hypercoagulable states
Use of other blood or plasma-derived products within three months prior to Visit 2
Patients with a past or present history of drug abuse or alcohol abuse within the preceding five years prior to baseline visit
Patients unable or unwilling to understand or comply with the study protocol
Participation in another interventional clinical study with investigational medicinal product (IMP) treatment currently or during the three months prior to Visit 2
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

Sites / Locations

MHAT Puls EOOD
St. Naum Hospital
Toronto General Hospital
Octapharma Research Site
Outpatient Clinic of Neurology
Regional Hospital Pardubice
Thomayer Faculty Hospital
University Medical Center Goettigen
Jahn Ferenc Del Pesti Korhaz
Szegedi Tudományegyetem ÁOK Neurológiai Klinika
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Klinika Neurologii
Wojewodzki Szpital Specjalistyczny W Olsztynie
Uniwersytecki Szpital Kliniczny
Theo Health S.R.L.
Institutul Clinic Fundeni
Spitalul Clinic Judetean de Urgenta "Sf.Apostol Andrei" Constanta
Republican Clinical Neurological Centre
Neurology Research Centre
Nizhny Novgorod Regional Clinical Hospital N.A. N.A.Semashko
National Medical Research Centre of Psychiatry and Neurology n.a. V.M.Bekhterev
City Multifield Hospital #2
Ivano Frankivsk National Medical University
National Medical Academy Of Postgraduate Education Named After P.L. Shupyk
Volyn Regional Clinical Hospital
Vinnytsia National Medical University
Municipal Institution Zaporizhzhya Regional Clinical Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

0.5 g/kg NewGam

1.0 g/kg NewGam

2.0 g/kg NewGam

Arm Description

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).

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).

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).

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

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)

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

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)

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.

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.

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.

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.

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).

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

Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)

Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS) scores

Full Information

NCT ID

NCT02638207

First Posted

December 16, 2015

Last Updated

January 28, 2021

Sponsor

Octapharma

1. Study Identification

Unique Protocol Identification Number

NCT02638207

Brief Title

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

Acronym

CIDP

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

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

September 27, 2017 (Actual)

Primary Completion Date

September 5, 2019 (Actual)

Study Completion Date

September 5, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Octapharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy

Keywords

Chronic Inflammatory Demyelinating Poly Neuropathy (CIDP)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

142 (Actual)

8. Arms, Groups, and Interventions

Arm Title

0.5 g/kg NewGam

Arm Type

Experimental

Arm Description

Arm Title

1.0 g/kg NewGam

Arm Type

Experimental

Arm Description

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).

Arm Title

2.0 g/kg NewGam

Arm Type

Experimental

Arm Description

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 Type

Drug

Intervention Name(s)

NewGam

Other Intervention Name(s)

Panzyga

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

Primary Outcome Measure Information:

Title

Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score

Description

Time Frame

at Week 24

Secondary Outcome Measure Information:

Title

Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score

Description

Time Frame

at Week 24

Title

Grip Strength Score

Description

Time Frame

at Week 24

Title

Inflammatory Rasch-built Overall Disability Scale (I-RODS Score)

Description

Time Frame

at Week 24

Title

Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score

Description

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)

Time Frame

Week 24

Title

Mean Change in Grip Strength

Description

Time Frame

Up to 24 weeks

Title

Inflammatory Rasch-built Overall Disability Scale (I-RODS)

Description

Time Frame

Up to 24 weeks

Title

Motor Nerves

Description

Time Frame

Up to 24 weeks

Title

Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale)

Description

Time Frame

Up to 24 weeks

Title

Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)

Description

Time Frame

24 weeks

Title

1 Point Decrease in the INCAT Disability Score

Description

Time to 1 point decrease (improvement of disability) in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score

Time Frame

24 weeks

Title

Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)

Description

Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS) scores

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 ) Patients currently depending on treatment with immunoglobulins or corticosteroids 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 Weakness of at least 2 limbs >18 to <80 years of age Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score between 2 and 9 (with a score of 2 coming exclusively from leg disability) Voluntarily given, fully informed written consent obtained from patient before any study-related procedures are conducted Exclusion Criteria: Unifocal forms of Chronic inflammatory demyelinating polyneuropathy (CIDP) Pure sensory Chronic inflammatory demyelinating polyneuropathy (CIDP) Multifocal motor neuropathy (MMN) with conduction block [van den Bergh et al., 2010] Patients who previously failed immunoglobulin treatment Treatment with immunomodulatory/suppressive agents (cyclosporin, methotrexate, mitoxantrone, mycophenolate mofetil or azathioprine) during the six months prior to baseline visit 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 Respiratory impairment requiring mechanical ventilation Myelopathy or evidence of central nervous system demyelination or significant persisting neurological deficits from stroke, or central nervous system (CNS) trauma Clinical evidence of peripheral neuropathy from another cause such as connective tissue disease or systemic lupus erythematosus (SLE) HIV infection, hepatitis, Lyme disease cancer (with the exception of basal cell skin cancer) IgM paraproteinemia with anti-myelin associated glycoprotein antibodies Diabetic neuropathy Cardiac insufficiency (New York Heart Association [NYHA] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease Severe liver disease (ALAT 3x > normal value) Severe kidney disease (creatinine 1.5x > normal value) Hepatitis B, hepatitis C or HIV infection 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) Body mass index (BMI) ≥40 kg/m2 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 Medical conditions whose symptoms and effects could alter protein catabolism and/or Immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome) Known Immunoglobulin A (IgA) deficiency with antibodies to Immunoglobulin A (IgA) History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of NewGam Known blood hyperviscosity, or other hypercoagulable states Use of other blood or plasma-derived products within three months prior to Visit 2 Patients with a past or present history of drug abuse or alcohol abuse within the preceding five years prior to baseline visit Patients unable or unwilling to understand or comply with the study protocol Participation in another interventional clinical study with investigational medicinal product (IMP) treatment currently or during the three months prior to Visit 2 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wolfgang Frenzel, MD

Organizational Affiliation

Octapharma

Official's Role

Study Director

Facility Information:

Facility Name

MHAT Puls EOOD

City

Blagoevgrad

ZIP/Postal Code

2700

Country

Bulgaria

Facility Name

St. Naum Hospital

City

Sofia

ZIP/Postal Code

1797

Country

Bulgaria

Facility Name

Toronto General Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2C4

Country

Canada

Facility Name

Octapharma Research Site

City

Montréal

ZIP/Postal Code

H3A2B4

Country

Canada

Facility Name

Outpatient Clinic of Neurology

City

Hradec Králové

ZIP/Postal Code

500 03

Country

Czechia

Facility Name

Regional Hospital Pardubice

City

Pardubice

ZIP/Postal Code

532 03

Country

Czechia

Facility Name

Thomayer Faculty Hospital

City

Prague

ZIP/Postal Code

140 00

Country

Czechia

Facility Name

University Medical Center Goettigen

City

Goettigen

ZIP/Postal Code

37075

Country

Germany

Facility Name

Jahn Ferenc Del Pesti Korhaz

City

Budapest

ZIP/Postal Code

1204

Country

Hungary

Facility Name

Szegedi Tudományegyetem ÁOK Neurológiai Klinika

City

Szeged

ZIP/Postal Code

6725

Country

Hungary

Facility Name

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Klinika Neurologii

City

Lublin

ZIP/Postal Code

20-954

Country

Poland

Facility Name

Wojewodzki Szpital Specjalistyczny W Olsztynie

City

Olsztyn

ZIP/Postal Code

10-561

Country

Poland

Facility Name

Uniwersytecki Szpital Kliniczny

City

Wrocław

ZIP/Postal Code

50-556

Country

Poland

Facility Name

Theo Health S.R.L.

City

Braşov

ZIP/Postal Code

500091

Country

Romania

Facility Name

Institutul Clinic Fundeni

City

Bucharest

ZIP/Postal Code

022328

Country

Romania

Facility Name

Spitalul Clinic Judetean de Urgenta "Sf.Apostol Andrei" Constanta

City

Constanţa

ZIP/Postal Code

900591

Country

Romania

Facility Name

Republican Clinical Neurological Centre

City

Kazan'

ZIP/Postal Code

420021

Country

Russian Federation

Facility Name

Neurology Research Centre

City

Moscow

ZIP/Postal Code

125367

Country

Russian Federation

Facility Name

Nizhny Novgorod Regional Clinical Hospital N.A. N.A.Semashko

City

Nizhny Novgorod

ZIP/Postal Code

603126

Country

Russian Federation

Facility Name

National Medical Research Centre of Psychiatry and Neurology n.a. V.M.Bekhterev

City

Saint Petersburg

ZIP/Postal Code

192019

Country

Russian Federation

Facility Name

City Multifield Hospital #2

City

Saint Petersburg

ZIP/Postal Code

194354

Country

Russian Federation

Facility Name

Ivano Frankivsk National Medical University

City

Ivano-Frankivs'k

ZIP/Postal Code

76008

Country

Ukraine

Facility Name

National Medical Academy Of Postgraduate Education Named After P.L. Shupyk

City

Kyiv

ZIP/Postal Code

4112

Country

Ukraine

Facility Name

Volyn Regional Clinical Hospital

City

Luts'k

ZIP/Postal Code

4300

Country

Ukraine

Facility Name

Vinnytsia National Medical University

City

Vinnytsia

ZIP/Postal Code

21005

Country

Ukraine

Facility Name

Municipal Institution Zaporizhzhya Regional Clinical Hospital

City

Zaporizhzhya

ZIP/Postal Code

69600

Country

Ukraine

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35038723

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs