Subcutaneous Immunoglobulin in De-novo CIDP (SIDEC) (SIDEC)

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

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.

Study Overview

• Status: Recruiting
• Conditions: CIDP - Chronic Inflammatory Demyelinating Polyneuropathy
• Intervention / Treatment: Biological: Immunoglobulin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lars Markvardsen, MD, PhD; Phone Number: +45 20231903; Email: larsmark@rm.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Not yet recruiting
    • Department of Neurology, Aalborg University Hospital
    • Contact: Izabella Obál, Md, PhD; Phone Number: 9766 2200; Email: i.obal@rn.dk
  • Aarhus C, Denmark, 8000
    • Recruiting
    • Department of Neurology, Aarhus University Hospital
    • Contact: Henning Andersen, DMSc; Email: hennande@rm.dk
    • Contact: Lars Markvardsen, MD; Phone Number: +45 7846 3337; Email: larsmark@rm.dk
    • Sub-Investigator: Lars Markvardsen, MD
    • Principal Investigator: Henning Andersen, DMSc
  • Copenhagen, Denmark, 2100
    • Not yet recruiting
    • Department of Neurology, Rigshospitalet, Copenhagen University Hospital
    • Contact: Tina D Jeppesen, MD,DMSc,PhD; Email: tina.dysgaard.jeppesen@regionh.dk
    • Principal Investigator: Tina D Jeppesen, MD,DMSc,PhD
  • Odense, Denmark, 5000
    • Not yet recruiting
    • Department of Neurology, Odense University Hospital
    • Contact: Søren Sindrup, MD, DMSc; Phone Number: +45 6541 2485; Email: soeren.sindrup@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patients treated with immunoglobulin intravenously (IVIG); 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; Randomization 1:1 to the same total dose of either SCIG or IVIG for 26 weeks of stable dose + 60 weeks of redcution.
Active Comparator: Patients treated with immunoglobulin subcutaneously (SCIG); 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; Randomization 1:1 to the same total dose of either SCIG or IVIG for 26 weeks of stable dose + 60 weeks of redcution.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The lowest dose of IVIG or SCIG reached during the 60 weeks of reduction (Fase II).	Monitored on ODSS and the same secondary parameters as in week 0 to 26	Week 26 to 86

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Odense University Hospital; Aarhus University Hospital; Rigshospitalet, Denmark; Aalborg University Hospital
• Investigators: Principal Investigator: Henning Andersen, MD,DMSc,PhD, Aarhus University, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2020
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 9, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Immunoglobulins, Intravenous; Injections, Subcutaneous
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyradiculoneuropathy; Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: AUH-2018-100; 2018-003592-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No