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

• ClinicalTrials.gov Identifier: NCT04589299
• Recruitment Status: Recruiting
• First Posted: October 19, 2020
• Last Update Posted: October 19, 2020
• Sponsor: University of Aarhus
• Collaborators: Rigshospitalet, Denmark; Aarhus University Hospital; Odense University Hospital; Aalborg University Hospital
• Information provided by (Responsible Party): University of Aarhus

Study Description

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.

Condition or disease	Intervention/treatment	Phase
CIDP - Chronic Inflammatory Demyelinating Polyneuropathy	Biological: Immunoglobulin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Parallel Study of Subcutaneous Versus Intravenous Immunoglobulin in Treatment-naïve Patients With Chronic Inflammatory Demyelinating Polyneuropathy
• Actual Study Start Date: June 4, 2020
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in disability [ Time Frame: Week 0 to 26 ]
   Evaluated with overall disability sum score (ODSS)

Secondary Outcome Measures :

1. Change in grip strength [ Time Frame: Week 0 to 26 ]
   Grip strength (JAMAR)
2. Change in general muscle strength [ Time Frame: Week 0 to 26 ]
   MRC-score
3. Change in sensation [ Time Frame: Week 0 to 26 ]
   INCAT-Sensory Sum Score (ISS)
4. Change in walking performance [ Time Frame: Week 0 to 26 ]
   10-meter-walk test (10-MWT)
5. Change in walking performance and imbalance [ Time Frame: Week 0 to 26 ]
   6-spot-step test (6-SST)
6. Change in dexterity [ Time Frame: Week 0 to 26 ]
   9-hole-peg test (9-HPT)
7. Change in quality of life [ Time Frame: Week 0 to 26 ]
   QoL (EQ-5D-5L incl. VAS)
8. Change in fatigue severity [ Time Frame: Week 0 to 26 ]
   Fatigue Severity Scale (FSS)
9. Change in pain severity [ Time Frame: Week 0 to 26 ]
   Neuropathic Pain Symptom Inventory (NPSI)
10. Change in disability [ Time Frame: Week 0 to 26 ]
    Rasch built overall disability scale (RODS)
11. Change in treatment satisfaction [ Time Frame: Week 2 to 26 ]
    Life Quality Index (LQI)
12. Serum samples [ Time Frame: Week 0 to 26 ]

    Plasma IgG (IgG1, IgG2, IgG3, IgG4) Hematology: hemoglobin, reticulocyte count, haptoglobin, bilirubin, plasma haemoglobin, leukocyte count, thrombocyte count.

    Inflammatory biomarkers: sCD163 and neurofilament

13. Fluctuations in the describing parameters (ODSS and RODS) in both groups (SCIG and IVIG) based on measurement at time points for treatment with IVIG [ Time Frame: 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)

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Contacts

Contact: Lars Markvardsen, MD, PhD; +45 20231903; larsmark@rm.dk

Locations

Denmark

Department of Neurology, Aalborg University Hospital; Not yet recruiting

Aalborg, Denmark, 9000

Contact: Izabella Obál, Md, PhD 9766 2200 i.obal@rn.dk

Department of Neurology, Aarhus University Hospital; Recruiting

Aarhus C, Denmark, 8000

Contact: Henning Andersen, DMSc hennande@rm.dk

Contact: Lars Markvardsen, MD +45 7846 3337 larsmark@rm.dk

Sub-Investigator: Lars Markvardsen, MD

Principal Investigator: Henning Andersen, DMSc

Department of Neurology, Rigshospitalet, Copenhagen University Hospital; Not yet recruiting

Copenhagen, Denmark, 2100

Contact: Tina D Jeppesen, MD,DMSc,PhD tina.dysgaard.jeppesen@regionh.dk

Principal Investigator: Tina D Jeppesen, MD,DMSc,PhD

Department of Neurology, Odense University Hospital; Not yet recruiting

Odense, Denmark, 5000

Contact: Søren Sindrup, MD, DMSc +45 6541 2485 soeren.sindrup@rsyd.dk

Sponsors and Collaborators

University of Aarhus

Rigshospitalet, Denmark

Aarhus University Hospital

Odense University Hospital

Aalborg University Hospital

Investigators

• Principal Investigator: Henning Andersen, MD,DMSc,PhD; Aarhus University, Aarhus University Hospital

More Information

• Responsible Party: University of Aarhus
• ClinicalTrials.gov Identifier: NCT04589299
• Other Study ID Numbers: AUH-2018-100; 2018-003592-34 ( EudraCT Number )
• First Posted: October 19, 2020
• Last Update Posted: October 19, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by University of Aarhus:

Immunoglobulins, Intravenous; Injections, Subcutaneous

Additional relevant MeSH terms:

Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; Immunologic Factors; Physiological Effects of Drugs