Evaluation of Subcutaneous Versus Intravenous Human Normal Immunoglobulin in Treatment-Naïve Patients with Chronic Inflammatory Demyelinating Polyneuropathy

The primary objective of this study is to evaluate the effect of subcutaneous immunoglobulin (SCIG) versus intravenous immunoglobulin (IVIG) in treatment-naïve patients with **chronic inflammatory demyelinating polyneuropathy (CIDP)** over a 26-week treatment period. This comparison is clinically relevant as it aims to determine the efficacy and potential benefits of SCIG, which may offer an alternative administration route with different safety and efficacy profiles compared to the traditional IVIG treatment.

Secondary objectives include evaluating a standardized reduction of the dosage regimen to identify the lowest effective dosage of immunoglobulin. This aspect of the study is crucial for optimizing treatment regimens, potentially reducing side effects, and improving patient compliance by minimizing the dosage while maintaining therapeutic efficacy.

The clinical trial focuses on individuals diagnosed with **Chronic inflammatory demyelinating polyneuropathy (CIDP)**, specifically targeting those with typical or pure motor CIDP who meet the European Federation of Neurological Societies / Peripheral Nerve Society (EFNS/PNS) clinical and electrophysiological criteria for definite or probable CIDP. The study population includes both male and female participants aged between 18 and 80 years. Participants are required to have an Overall Disability Sum Score (ODSS) greater than 1. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, parallel study to evaluate the efficacy of subcutaneous immunoglobulin (SCIG) versus intravenous immunoglobulin (IVIG) in treatment-naïve patients with **chronic inflammatory demyelinating polyneuropathy (CIDP)**. The trial will be conducted over a period of 74 weeks, with the primary objective being to assess changes in the Overall Disability Sum Score (ODSS) over a 26-week treatment phase. The study will involve two groups: one receiving Hizentra 200 mg/ml solution for subcutaneous injection and the other receiving Privigen 100 mg/ml solution for infusion. Both products contain **human normal immunoglobulin** as the active substance.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-80 years) and ODSS > 1. Following randomization, participants will attend regular follow-up visits to monitor changes in disability, muscle strength, sensory parameters, and quality of life. These visits will also include assessments of serum samples and hematology parameters. The end-of-study visit will occur at the conclusion of the 74-week period, or earlier if the participant reaches the lowest effective dosage of immunoglobulin.

The expected length of participant involvement is up to 74 weeks, with conditions for early termination including adverse events, withdrawal of consent, or failure to adhere to the study protocol. The trial will measure both primary and secondary endpoints, including changes in muscle strength, functional ability, and treatment satisfaction. The study is not classified as low intervention and is conducted under the authorization of CSL Behring GmbH, with the trial phase categorized as phase II.

The clinical trial involves the administration of **Hizentra**, a 200 mg/ml solution for subcutaneous injection, as the experimental medication. Hizentra contains **human normal immunoglobulin** as its active substance, which is a structurally diverse, blood-derived substance. The pharmaceutical form is a solution for injection, specifically designed for subcutaneous administration. The maximum daily dose of Hizentra is 9 grams, with a total maximum dose of 65 grams over a treatment period of 74 days. The administration schedule is determined by the study protocol, and participant compliance is monitored throughout the trial. Hizentra is manufactured by CSL Behring GmbH and is authorized for use in the European Union under the marketing authorization number EU/1/11/687/012.

The comparator treatment in this study is **Privigen**, a 100 mg/ml solution for infusion. Like Hizentra, Privigen also contains **human normal immunoglobulin** as its active ingredient, derived from blood. The pharmaceutical form is a solution for infusion, intended for intravenous administration. The maximum daily dose for Privigen is 60 grams, with a total maximum dose of 240 grams over the same 74-day treatment period. The dosing schedule is aligned with the study's objectives, and adherence to the regimen is closely monitored. Privigen is also produced by CSL Behring GmbH and holds the marketing authorization number EU/1/08/446/006 in the European Union.

Both treatments are evaluated in a randomized, parallel study to assess their efficacy in treatment-naïve patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The trial's main objective is to compare the effects of subcutaneous immunoglobulin (SCIG) versus intravenous immunoglobulin (IVIG) over a 26-week treatment period. No additional non-experimental treatments, such as placebo or standard-of-care therapy, are utilized in this study. The trial ensures rigorous monitoring of drug administration and participant compliance to maintain the integrity of the study results.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint involves measuring the change in the Overall Disability Sum Score (ODSS) using a questionnaire from baseline until the end of phase I, which lasts 26 weeks. Additionally, the ODSS will be measured from the start of phase II until the lowest effective dosage of immunoglobulin is reached, up to 60 weeks.

Secondary endpoints include changes in parameters related to muscle strength and sensory function, such as grip strength, MRC-score, and INCAT Sensory Sum Score (ISSS). Functional ability will be evaluated using the 10-meter-walk test (10-MWT), 6-spot-step test (6-SST), and 9-hole-peg test (9-HPT). Other secondary endpoints will assess changes in disability, quality of life, pain, and treatment satisfaction, utilizing tools like the EQ-5D-5L for quality of life, Fatigue Severity Scale (FSS), Neuropathic Pain Symptom Inventory (NPSI), Rasch built overall disability scale (RODS), and Treatment Satisfaction Questionnaire for Medication (TSQM).

Biomarker levels will be monitored through serum samples, specifically measuring plasma **IgG**. Hematological parameters such as hemoglobin, reticulocyte count, haptoglobin, bilirubin, plasma hemoglobin, leukocyte count, and thrombocyte count will also be evaluated. Fluctuations in these parameters will be observed at predefined time points in relation to intravenous immunoglobulin (IVIG) infusions, specifically at weeks 0, 4, and 20 compared to weeks 2, 14, and 26.