Subcutaneous Immunoglobulin in De-novo CIDP (SIDEC)

Phase 4

Recruiting

• Conditions: CIDP - Chronic Inflammatory Demyelinating Polyneuropathy
• Interventions: Biological: Immunoglobulin

• Registration Number: NCT04589299
• Lead Sponsor: University of Aarhus

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2020-06-04
• Study First Submitted: 2020-09-09
• Study First Submitted QC: 2020-10-09
• Study First Posted: 2020-10-19
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-15
• Last Update Posted: 2024-05-17
• Primary Completion: 2030-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

1. Motor distal latency prolongation ≥50% above ULN in two nerves (excluding median neuropathy at the wrist from carpal tunnel syndrome), or
2. Reduction of motor conduction velocity ≥30% below LLN in two nerves, or
3. Prolongation of F-wave latency ≥30% above ULN in two nerves (≥50% if amplitude of distal negative peak CMAP ≤80% of LLN values), or
4. 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
5. 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
6. Abnormal dispersion (≥30% duration increase between the proximal and distal negative peak CMAP) in ≥2 nerves, or
7. 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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients treated with immunoglobulin intravenously (IVIG)	Immunoglobulin	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%).
Patients treated with immunoglobulin subcutaneously (SCIG)	Immunoglobulin	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%).

Primary Outcome Measures

Name	Time	Method
Change in disability	Week 0 to 26	Evaluated with overall disability sum score (ODSS)

Secondary Outcome Measures

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

Trial Locations

Locations (4)

Department of Neurology, Rigshospitalet, Copenhagen University Hospital; 🇩🇰 Copenhagen, Denmark

Department of Neurology, Odense University Hospital; 🇩🇰 Odense, Denmark

Department of Neurology, Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

Department of Neurology, Aarhus University Hospital; 🇩🇰 Aarhus C, Denmark