Clinical trial NCT04589299: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: CIDP - Chronic Inflammatory Demyelinating Polyneuropathy
Keywords: Immunoglobulins, Intravenous
Injections, Subcutaneous
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Aarhus University Hospital
name: Odense University Hospital
name: Aalborg University Hospital
First posted: 2020-10-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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

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)

Primary outcomes:
measure: Change in disability
timeFrame: Week 0 to 26
Secondary outcomes:
measure: Change in grip strength
timeFrame: Week 0 to 26
measure: Change in general muscle strength
timeFrame: Week 0 to 26
measure: Change in sensation
timeFrame: Week 0 to 26
measure: Change in walking performance
timeFrame: Week 0 to 26
measure: Change in walking performance and imbalance
timeFrame: Week 0 to 26
measure: Change in dexterity
timeFrame: Week 0 to 26
measure: Change in quality of life
timeFrame: Week 0 to 26
measure: Change in fatigue severity
timeFrame: Week 0 to 26
measure: Change in pain severity
timeFrame: Week 0 to 26
measure: Change in disability
timeFrame: Week 0 to 26
measure: Change in treatment satisfaction
timeFrame: Week 2 to 26
measure: Serum samples
timeFrame: Week 0 to 26
measure: Fluctuations in the describing parameters (ODSS and RODS) in both groups (SCIG and IVIG) based on measurement at time points for treatment with IVIG
timeFrame: Week 0 to 26
Other outcomes:
measure: The lowest dose of IVIG or SCIG reached during the 60 weeks of reduction (Fase II).
timeFrame: Week 26 to 86
Locations:
city: Aalborg
country: Denmark
facility: Department of Neurology, Aalborg University Hospital
city: Aarhus C
country: Denmark
facility: Department of Neurology, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Neurology, Rigshospitalet, Copenhagen University Hospital
city: Odense
country: Denmark
facility: Department of Neurology, Odense University Hospital
Study officials:
affiliation: Aarhus University, Aarhus University Hospital
name: Henning Andersen, MD,DMSc,PhD
role: PRINCIPAL_INVESTIGATOR
References: