Evaluation of Subcutaneous Daratumumab in Patients with Moderate to Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

The primary objective of this pilot study is to evaluate the **feasibility** and **safety** of subcutaneous injections of the anti-CD38 antibody **daratumumab** in patients with moderate to severe **Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)**. This is clinically relevant as it aims to determine the potential of daratumumab, a medication primarily used in oncology, for a condition characterized by profound fatigue and other debilitating symptoms, which currently lacks effective treatments.

Secondary objectives include assessing the **efficacy**, measured by changes in secondary endpoints, to further understand the therapeutic potential and impact of daratumumab on ME/CFS symptoms.

The clinical trial focuses on individuals diagnosed with **Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)**, specifically targeting those with moderate to severe manifestations of the condition. The study population includes both male and female participants, aged between 18 to 65 years. Participants are required to have a disease duration of at least two years and a defined onset of ME/CFS, such as post-infection. Additionally, a baseline Natural Killer (NK) cell count greater than 130 x 10^6/L is necessary for inclusion. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **feasibility** and **safety** of subcutaneous injections of **daratumumab** in patients with moderate to severe **Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)**. This is a Phase II, randomized, double-blind, controlled trial. The trial is expected to commence recruitment on October 1, 2024, and conclude by December 31, 2028. The study will involve a maximum treatment period of 52 weeks, with participants receiving a maximum total dose of 12,600 mg of **DARZALEX 1800 mg solution for injection**. The primary endpoint is the assessment of safety and tolerability, measured by treatment-emergent adverse events. Secondary endpoints include changes in SF36 domain scores, DSQ-SF scores, patient-reported physical function, and steps per 24 hours over a 40-week follow-up period from the start of the intervention.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 to 65 years), disease duration (at least two years), and baseline **Natural Killer (NK) cell count** (>130 x 10^6/L). Following the screening, eligible participants will be randomized and begin the treatment phase. Follow-up visits will be scheduled to monitor safety, efficacy, and any adverse events. The end-of-study visit will occur after the completion of the treatment period, where final assessments will be conducted. The expected length of participant involvement is approximately 52 weeks, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety.

The clinical trial involves the administration of **DARZALEX**, a pharmaceutical product containing the active substance **daratumumab**. This medication is provided in the form of a **solution for injection** and is specifically designed for subcutaneous administration. Each dose contains 1800 mg of **daratumumab**, with a maximum daily dose of 1800 mg and a cumulative maximum dose of 12600 mg over the course of the treatment. The treatment period is set to a maximum of 52 weeks. **DARZALEX** is manufactured by Janssen-Cilag International NV and is classified under the ATC code L01FC01. The active substance, **daratumumab**, is a protein of other origin, specifically an anti-CD38 antibody, which is utilized in this study to evaluate its feasibility and safety in patients with moderate to severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of **DARZALEX** to assess its effects. The study protocol includes monitoring participant compliance with the dosing schedule to ensure accurate assessment of the treatment's safety and feasibility. Participants will receive the medication via subcutaneous injection, adhering to the specified dosing regimen throughout the trial duration.

Efficacy in the clinical trial will be assessed using several secondary endpoints. These include changes in SF36 domain scores, specifically focusing on Physical Function and Bodily Pain, from the baseline or run-in period through a 40-week follow-up from the start of the intervention. Additionally, changes in DSQ-SF scores will be evaluated over the same period. Patient-reported physical function and changes in steps per 24 hours will also be measured from baseline through the 40-week follow-up. These parameters will be collected and analyzed to determine the impact of the treatment on patients with moderate to severe **Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)**. The assessment will utilize validated scales and patient-reported outcomes to ensure accurate and reliable data collection throughout the trial duration.