Subcutaneous Immunoglobulin in De-novo CIDP (SIDEC)

Official title

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

Overview

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.

Interventions

• Biological Immunoglobulin
  Randomization 1:1 to the same total dose of either SCIG or IVIG for 26 weeks of stable dose + 60 weeks of redcution.

Primary outcome measures

• Change in disability [Time frame: Week 0 to 26]

Secondary outcome measures (12)

• Change in grip strength [Time frame: Week 0 to 26]
• Change in general muscle strength [Time frame: Week 0 to 26]
• Change in sensation [Time frame: Week 0 to 26]
• Change in walking performance [Time frame: Week 0 to 26]
• Change in walking performance and imbalance [Time frame: Week 0 to 26]
• Change in dexterity [Time frame: Week 0 to 26]
• Change in quality of life [Time frame: Week 0 to 26]
• Change in fatigue severity [Time frame: Week 0 to 26]
• Change in pain severity [Time frame: Week 0 to 26]
• Change in disability [Time frame: Week 0 to 26]
• Change in treatment satisfaction [Time frame: Week 2 to 26]
• Serum samples [Time frame: Week 0 to 26]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Denmark · 4 centers

• Department of Neurology, Aalborg University Hospital — Aalborg
• Department of Neurology, Aarhus University Hospital — Aarhus C
• Department of Neurology, Rigshospitalet, Copenhagen University Hospital — Copenhagen
• Department of Neurology, Odense University Hospital — Odense

Identifiers

NCT: NCT04589299 · AUH-2018-100 · 2018-003592-34

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗