Prospective, double-blind, randomized, multicenter phase III study evaluating efficacy and safety of three different dosages of NewGam in patients with chronic inflammatory neuropathy.

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-005443-14-DE
• Date of registration: 05/04/2017
• Prospective Registration: Yes
• Primary sponsor: Octapharma Pharmazeutika Produktionsges.m.b.H.
• Public title: Prospective, double-blind, randomized, multicenter phase III study evaluating efficacy and safety of three different dosages of NewGam in patients with chronic inflammatory neuropathy.
• Scientific 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.
• Date of first enrolment: 28/04/2017
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005443-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Bulgaria, Canada, Czech Republic, Denmark, Germany, Hungary, Poland, Romania, Russian Federation, Sweden, Ukraine

Contacts

• Name: Global Clinical Project Manager
• Affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H.

• Name: Global Clinical Project Manager
• Affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H.

Key inclusion & exclusion criteria

Inclusion criteria:
1.Patients with diagnosis of definite or probable CIDP according to the EFNS/PNS Guideline 2010; including patients with Multifocal Acquired Demyelinating Sensory And Motor Neuropathy (MADSAM) or pure motor 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 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1.Unifocal forms of CIDP
2.Pure sensory CIDP
3.MMN with conduction block
4.Patients who previously failed immunoglobulin therapy
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:
a.connective tissue disease or systemic lupus erythematosus (SLE)
b.HIV infection, hepatitis, Lyme disease
c.cancer (with the exception of basal cell skin cancer)
d.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 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 they don’t receive adequate substitution therapy
18.Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome)
19.Known IgA deficiency with antibodies to 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 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 vasect

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Inflammatory Demyelinating Poly(radiculo)-neuropathy (CIDP)
MedDRA version: 20.0 Level: PT Classification code 10057645 Term: Chronic inflammatory demyelinating polyradiculoneuropathy System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Trade Name: PANZYGA
Product Name: NewGam
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Immunoglobulin G
CAS Number: 308067-58-5
Other descriptive name: IMMUNOGLOBULIN G
Concentration unit: % percent
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous drip use (Noncurrent)

Primary Outcome(s)

Secondary Objective: Secondary:
•To assess the effect of 0.5 g/kg and 2.0 g/kg NewGam every three weeks in patients with active CIDP based on the percentage of responders at Week 24 compared to patients on 1.0 g/kg NewGam every three weeks
•To evaluate the safety of NewGam administration using various dosages in patients with CIDP
•To further evaluate the beneficial effect of three NewGam dosages in patients with CIDP by assessing different parameters/scores/scales
Exploratory:
•To assess the primary and secondary objectives at three weeks after having provided rescue medication (if applicable)
•To further evaluate the beneficial effect of NewGam administration in patients with CIDP by additional assessments/scores including quality of life (QoL) measures

Timepoint(s) of evaluation of this end point: Week 24

Primary end point(s): Primary
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 INCAT disability score (a scale from 0 to 10, from healthy to unable to make any purposeful movements with arms and/or legs)

Main Objective: Primary:
•To provide confirmatory data on the effect of 1.0 g/kg NewGam every three weeks in patients with active CIDP based on the percentage of responders at Week 24, which should corroborate the existing evidence on efficacy of IGIV in CIDP as known from published literature.

Secondary Outcome(s)

Secondary end point(s): Secondary
1-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 INCAT disability score
2- 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 kPa
3- 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 I-RODS scores using the MCID concept related to the varying standard errors (MCID-SE) as recently demonstrated.
4- Time to first confirmed worsening on the adjusted INCAT disability scale by at least 1 point from the value at baseline (Week 0)
5 - Mean change from baseline (Week 0) to Termination Visit in
a.- grip strength of both hands (assessed by Martin Vigorimeter)
b.- Inflammatory Rasch-built overall disability sum score (I-RODS using the concept of MCID-SE as recently reported; Appendix 1) and number of improvers
c.- sum of the distal evoked amplitude of 4 right sided and 4 left sided motor nerves (peroneal, tibial, ulnar and median)
d.- Pain Intensity Numeric Rating Scale (PI-NRS)
6- Time to first confirmed worsening on the I-RODS scale
7- Time to 1 point decrease (improvement of disability) in adjusted INCAT disability score
8-Time to decrease in I-RODS scores

Exploratory:
1- Mean change from baseline (Week 0) to Termination Visit in:
a.- modified Fatigue Severity Scale (FSS; 7-item scale from 0-21 points; see Appendix 2)
b.- number of improvers by at least 4 points in the MRC sum score (according to the universal rule of minimal clinical important difference)
c.- SF-36 Health Survey physical composite score (PCS), mental composite score (MCS) and their 8 health domains (see Appendix 3)
d.- additional NCS analyses (e.g. individual nerve analysis)
2 - Time to decrease in MRC sum score to or below baseline value after temporary improvement (increase)
Safety (throughout the entire Wash-out and Dose-evaluation Phases):
1 - Occurrence of all adverse events (AEs)
2 - Short term tolerance parameters including vital signs
3- Physical/neurological examination
4 - Laboratory parameters (hematology and clinical chemistry) and tests for viral safety

Timepoint(s) of evaluation of this end point: Week 24

Secondary ID(s)

NGAM-08

14096

NCT02638207

Source(s) of Monetary Support

Octapharma Pharmazeutika Produktionsges.m.b.H.

Ethics review

Status: Approved
Approval date:
Contact: