Subcutaneous Immunoglobulin in De-novo CIDP (SIDEC)

Study Overview
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Brief Summary
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SIDEC - (Subcutaneous Immunoglobulin in De-novo CIDP) ia a study designed as a randomized, parallel study with an open-label extension phase. The aims are to compare the effect of SCIG and IVIG in 60 treatment-naïve CIDP patients, and to detect the lowest effective dosage for maintenance treatment.

Detailed Description
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In fase I the patients are followed for 26 weeks on a fixed dose of 0.54 g/kg/week in the SCIG group (total 14 g/kg) and 2 g/kg/4week in the IVIG group (total 14 g/kg). The patients automatically continue in fase II in which treatment is reduced every 12 weeks (90%, 75%, 50%, 25% and 0%) over a course 60 weeks. The patients are evaluated at every visit with overall disability sum score (ODSS), grip strength, medical research council score (MRC-score), INCAT-Sensory Sum Score (ISS), 10-meter-walk test (10-MWT), 6-spot-step test (6-SST), 9-hole-peg test (9-HPT), quality of life (EQ-5D-5L), Fatigue Severity Scale (FSS), Neuropathic Pain Symptom Inventory (NPSI), Rasch built overall disability scale (RODS) and Life Quality Index (LQI) and blood samples.

Official Title
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Randomized, Parallel Study of Subcutaneous Versus Intravenous Immunoglobulin in Treatment-naïve Patients With Chronic Inflammatory Demyelinating Polyneuropathy

Conditions
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CIDP - Chronic Inflammatory Demyelinating Polyneuropathy

Intervention / Treatment
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* Biological: Immunoglobulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfilling EFNS/PNS criteria for definite, probable or pure motor CIDP. No previous treatment with IVIG or SCIG. Age ≥ 18. ODSS ≥ 2 - either (arm/leg): 1/1, 2/0 or 0/2 at the time of inclusion. Clinical criteria for typical CIDP Chronically progressive, stepwise, or recurrent symmetric proximal and distal weakness and sensory dysfunction of all extremities, developing over at least 2 months; cranial nerves may be affected. Absent or reduced tendon reflexes in all extremities. Criteria for pure motor CIDP • Pure motor affection; otherwise as for typical CIDP. Electrophysiological criteria for CIDP Motor distal latency prolongation ≥50% above ULN in two nerves (excluding median neuropathy at the wrist from carpal tunnel syndrome), or Reduction of motor conduction velocity ≥30% below LLN in two nerves, or Prolongation of F-wave latency ≥30% above ULN in two nerves (≥50% if amplitude of distal negative peak CMAP ≤80% of LLN values), or Absence of F-waves in two nerves of these nerves have distal negative peak CMAP amplitudes ≥20% of LLN + ≥1 other demyelinating parameter in ≥1 other nerve, or Partial motor conduction block: ≥50% amplitude reduction of the proximal negative peak CMAP relative to distal, if distal negative peak CMAP >20% of LLN, in two nerves, or in one nerve + ≥1 other demyelinating parameter in ≥1 other nerve, or Abnormal dispersion (≥30% duration increase between the proximal and distal negative peak CMAP) in ≥2 nerves, or Distal CMAP duration (interval between onset of the first negative peak an return to baseline of the last negative peak) increase in ≥1 nerve (median ≥6.6 ms, ulnar ≥6.7 ms, peroneal ≥7.6 ms, tibial ≥8.8 ms) + ≥1 other demyelinating parameter in ≥1 other nerve Electrophysiological criteria for probable CIDP (a) ≥30% amplitude reduction of the proximal negative peak CMAP relative to distal, excluding the posterior tibial nerve, if distal negative peak CMAP ≥20% of LLN, in two nerves, or in one nerve + ≥1 other demyelinating parameter in ≥1 other nerve Exclusion Criteria: Other causes of neuropathy Increased risk of thromboembolism Pregnancy (Plasma HCG is tested at inclusion in all fertile women) Breast feeding Malignancy Severe medical disease Other immune modulating treatment than low dose steroid (prednisolon < 25 mg daily) within the last 6 months prior to inclusion Hepatitis B or C or HIV infection (screening at inclusion) Known IgA deficiency Known allergy to consents in PRIVIGEN or HIZENTRA Body weight > 120 kg After treatment initiation: Pregnancy Serious medical disease that affects treatment or examinations Non-compliance to treatment Initiation of other immune modulating therapy Unacceptable side effects Withdrawal of consent to participate (drop-out)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients treated with immunoglobulin intravenously (IVIG)<br>Immunoglobulin (PRIVIGEN) intravenously 2 g/kg/4week for 26 weeks. After this 60 weeks of reduction every 12 weeks (90%, 75%, 50%, 25% and 0%). | Biological: Immunoglobulin<br>* Randomization 1:1 to the same total dose of either SCIG or IVIG for 26 weeks of stable dose + 60 weeks of redcution.<br>|
| Active Comparator: Patients treated with immunoglobulin subcutaneously (SCIG)<br>Immunoglobulin (HIZENTRA) subcutaneously 0.54 g/kg/week for 26 weeks. After this 60 weeks of reduction every 12 weeks (90%, 75%, 50%, 25% and 0%). | Biological: Immunoglobulin<br>* Randomization 1:1 to the same total dose of either SCIG or IVIG for 26 weeks of stable dose + 60 weeks of redcution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in disability | Evaluated with overall disability sum score (ODSS) | Week 0 to 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in grip strength | Grip strength (JAMAR) | Week 0 to 26 | 
| Change in general muscle strength | MRC-score | Week 0 to 26 | 
| Change in sensation | INCAT-Sensory Sum Score (ISS) | Week 0 to 26 | 
| Change in walking performance | 10-meter-walk test (10-MWT) | Week 0 to 26 | 
| Change in walking performance and imbalance | 6-spot-step test (6-SST) | Week 0 to 26 | 
| Change in dexterity | 9-hole-peg test (9-HPT) | Week 0 to 26 | 
| Change in quality of life | QoL (EQ-5D-5L incl. VAS) | Week 0 to 26 | 
| Change in fatigue severity | Fatigue Severity Scale (FSS) | Week 0 to 26 | 
| Change in pain severity | Neuropathic Pain Symptom Inventory (NPSI) | Week 0 to 26 | 
| Change in disability | Rasch built overall disability scale (RODS) | Week 0 to 26 | 
| Change in treatment satisfaction | Life Quality Index (LQI) | Week 2 to 26 | 
| Serum samples | Plasma IgG (IgG1, IgG2, IgG3, IgG4) Hematology: hemoglobin, reticulocyte count, haptoglobin, bilirubin, plasma haemoglobin, leukocyte count, thrombocyte count. Inflammatory biomarkers: sCD163 and neurofilament | Week 0 to 26 | 
| Fluctuations in the describing parameters (ODSS and RODS) in both groups (SCIG and IVIG) based on measurement at time points for treatment with IVIG | Average value of examinations made at week 0, 4 and 20 (prior to IVIG infusion) Average value of examinations made at week 2, 14 and 26 (2 weeks after IVIG infusion) | Week 0 to 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunoglobulins, Intravenous, Injections, Subcutaneous