CD19-B Cell Depletion in PAIS-ME/CFS Patients

NCT07724834 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: PIONEER_PAIS
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Post-acute infection syndromes (PAIS) are long-lasting health problems that can develop after an infection. They include post-COVID-19 syndrome and similar illnesses following other infections. Some people with PAIS develop myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a serious and disabling illness that can greatly limit everyday activities. People with ME/CFS may experience severe fatigue, reduced physical and mental function, pain, sleep problems, and problems with the regulation of heart rate and blood pressure. A key feature is post-exertional malaise (PEM), in which symptoms become worse after physical or mental activity. The biological causes of PAIS and ME/CFS are not fully understood, and there is currently no established treatment that targets the underlying disease process. Research suggests that changes in the immune system may contribute to PAIS and ME/CFS in some patients. In particular, B cells (a type of immune cell) and autoantibodies (antibodies that react with the body's own structures) may play a role. Previous studies of immunoadsorption, a procedure that removes antibodies from the blood, have shown improvements in some patients with ME/CFS. These findings support further investigation of treatments that target B cells in selected patients. The PIONEER\_PAIS study will investigate whether inebilizumab can improve physical function in adults with PAIS who meet the diagnostic criteria for ME/CFS. The study includes a selected group of patients with evidence of autoantibodies and immune activation who previously improved after immunoadsorption but later experienced worsening of their symptoms. Inebilizumab is a monoclonal antibody that targets CD19, a protein found on B cells, and leads to the depletion of these cells. Participants will be randomly assigned to receive either inebilizumab or placebo (saline solution) as an infusion into a vein. Inebilizumab will be given at a dose of 300 mg on Day 1, Day 15, and Week 24. The study is double-blind, meaning that neither the participants nor the study team assessing them will know which treatment they receive. The main research question is whether treatment with inebilizumab leads to a greater improvement in physical function (PF) than placebo. PF will be measured using the PF scale of the SF-36 health questionnaire, comparing the change from the start of the study to Month 9 (Week 36). The study will also examine other aspects of health and daily functioning, including fatigue, post-exertional malaise, pain and headache, disability, symptoms related to the autonomic nervous system, muscle strength and fatigability, heart rate and blood pressure responses during standing, daily step count, and cognitive function. Adverse events will be monitored to assess the safety of the treatment. In addition, the study includes biomarker research focusing on B cells, autoantibodies, and other markers in the blood. This research aims to explore biological characteristics that may be associated with response to treatment and may help inform future studies of B-cell-targeted treatment in PAIS and ME/CFS.

Conditions

Post-acute Infectious Syndrome (PAIS); Post-COVID 19 Condition (PCC or Long COVID); Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Keywords

PAIS; Long COVID; ME/CFS; Fatigue

Outcome Measures

Primary Outcomes (1)

• Improvement in Physical Function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36) comparing Inebilizumab with placebo

  The SF-36 is an established and widely used measure of health-related quality of life. The PF domain assesses limitations in ten activities related to mobility and self-care, such as walking specified distances, carrying groceries, bathing, and dressing. Scores are weighted and transformed to a scale ranging from 0 (severe functional limitations) to 100 (no functional limitations). The intra-patient change in SF-36 PF will be assessed from baseline to month 9 (week 36).

  9 months (36 weeks) after first IMP administration

Secondary Outcomes (11)

• Difference in responder rate in Physical Function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36) comparing Inebilizumab with placebo

  9 months (36 weeks) after first IMP administration

• Improvement in other sub-domains of the Short Form 36 Health Survey Questionnaire (SF-36) comparing Inebilizumab with placebo

  9 months (36 weeks) after first IMP administration

• Improvement in severity of muscle pain and headache as measured by the Canadian Consensus Criteria (CCC) Symptom Score

  9 months (36 weeks) after first IMP administration

• Improvement in symptoms of ME/CFS as measured by Canadian Consensus Criteria (CCC) Symptom Score

  9 months (36 weeks) after first IMP administration

• Improvement in functional disability as measured by the Bell Disability Scale

  9 months (36 weeks) after first IMP administration

Study Arms (2)

Inebilizumab (Uplizna®)

ACTIVE COMPARATOR

Tested IMP: Inebilizumab (Uplizna®), an anti-CD19 monoclonal antibody. Authorization status: Not authorized for the targeted indication; inebilizumab is authorized for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who are AQP4-IgG seropositive. Inebilizumab used in this trial is a commercially available medicinal product manufactured by Amgen Europe B.V., with marketing authorization number EU/1/21/1602/001. Administration: The treatment period comprises three intravenous administrations of 300 mg inebilizumab: on Day 1, Day 15, and after 6 months, followed by a 3-months follow-up period. Each infusion will be preceded by methylprednisolone 125 mg and dimetindene maleate 4 mg administered intravenously in 100 ml of 0.9% sodium chloride solution, and paracetamol 500 mg administered orally, to reduce the risk of infusion-related reactions (premedication). The dosing regimen follows the authorized regimen for AQP4-IgG-seropositive NMOSD.

Drug: Inebilizumab

Placebo

PLACEBO COMPARATOR

Comparator IMP: Saline solution (0.9% sodium chloride solution) for intravenous infusion. Authorization status: Saline solution is routinely used in clinical practice; it is used as a placebo comparator in this trial and has no expected therapeutic effect on PAIS or ME/CFS. Administration: The treatment period comprises three intravenous placebo administrations: on Day 1, Day 15, and after 6 months, followed by a 3-month follow-up period. To maintain blinding, each placebo infusion is preceded by the same premedication as the inebilizumab infusion: methylprednisolone 125 mg and dimetindene maleate 4 mg administered intravenously in 100 ml of 0.9% sodium chloride solution, and paracetamol 500 mg administered orally.

Drug: Placebo

Interventions

Inebilizumab DRUG

The treatment period comprises three intravenous administrations of 300 mg inebilizumab: on Day 1, Day 15, and after 6 months, followed by a 3-months follow-up period. Each infusion will be preceded by a premediaction (methylprednisolone 125 mg, dimetindene maleate 4 mg, and paracetamol 500 mg) to reduce the risk of infusion-related reactions.

Also known as: Anti-CD19 monoclonal antibody

Inebilizumab (Uplizna®)

Placebo DRUG

The treatment period comprises three intravenous placebo administrations: on Day 1, Day 15, and after 6 months, followed by a 3-month follow-up period. To maintain blinding, each placebo infusion is preceded by the same premedication (methylprednisolone 125 mg, dimetindene maleate 4 mg, and paracetamol 500 mg) as the inebilizumab infusion.

Also known as: Saline solution (0.9% sodium chloride solution)

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female/diverse adults who are 18-65 years old at time of enrollment
• Subject is able and willing to give informed consent
• Signed informed consent prior to initiation of any trial related measure
• Diagnosis of PAIS as defined by WHO for PCS, wi th other infectious triggers
• Diagnosis of ME/CFS according to CCC criteria with PEM \> 14 hours = PAIS/CFS
• Documented clinical response to immunoadsorption (minimum increase in SF-36 PF of 10 points at week 8) followed by consecutive worsening of symptoms (minimum decrease in SF-36 PF of 10 points for at least 3 months)
• Evidence of activated pro inflammatory immune cell status
• Bell score at screening visit: 30-60
• Normal thyroid function or sufficiently medicated dysfunction
• For women of childbearing potential (WOCBP):
• Confirmed post-menopausal state, defined as amenorrhea for at least 12 months, or
• If being of childbearing potential: Negative highly sensitive urine or serum pregnancy test before randomization, and practicing a highly effective birth control method (failure rate of less than 1%)

You may not qualify if:

• Contraindication against IMP or AMP
• Hypersensitivity to the active substance or any of the other ingredients
• Vaccination less or up to 4 weeks before first visit
• Immunomodulative therapy \< 3 month before screening visit
• Concomitant and previous use of IMP
• Known SARS-CoV-2 or other infection related organ damage/comorbidity
• Pre-infection history of chronic fatigue syndrome or other fatigue syndromes that are due to associated diseases (e.g., cancer, autoimmune diseases \[patients with a preexcisting Hashimoto thyroiditis and/or fibromyalgia without fatigue syndromes can be included\])
• Serious infections, including active or latent and chronic infections such as tuberculosis, HIV, Lues, hepatitis B and C
• Immune- and immunoglobulin-deficiency or severely immunocompromised condition
• Any other severe or unstable medical conditions (immune, cardiovascular, respiratory, endocrine, gastrointestinal, hematological, neurological, psychiatric, systemic) or any other condition deemed by the Investigator to pose unacceptable risk, interfere with IP evaluation, or confound study results.
• At screening : aspartate transaminase (AST) \> 2.5 × upper limit of normal (ULN), alanine transaminase (ALT) \> 2.5 × ULN, total bilirubin \> 1.5 × ULN (unless due to Gilbert's syndrome), platelet count \< 75,000/µL, hemoglobin \< 8 g/dL, eGFR\<30 mL/min/1.73 m², total immunoglobulin \< 900 mg/dL, absolute neutrophil count \< 1200 cells/µL, CD4 T lymphocyte count \< 300 cells/µL
• Concomitant diseases or health constellations causing general physical weakness or fatigue, like: i) renal insufficiency with eGR\< 15 or diyalsis, ii) impaired liver function with elevated liver enzymes a) Aspartate aminotransferase (AST) and b) Alanin-Aminotransferase (ALT), both \>35 U/l for women or \> 50 U/l for men, iii) anemia with low hemoglobin-concentrations \<13,0 g/dL for males and \<12,0 g/dL for females, and iv) adipositas grades II or higher (BMI: ≥ 35 kg/m 2) at screening
• Subject is pregnant or breastfeeding
• Subject is institutionalized by order of court or public authority
• Subject who might be dependent on the sponsor, the investigator, or the trial site

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

MeSH Terms

Conditions

Hemophilia B; Post-Acute COVID-19 Syndrome; Fatigue Syndrome, Chronic; Fatigue

Interventions

inebilizumab; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Judith Bellmann-Strobl, MD

  Charité - Universitätsmedizin Berlin, Berlin, Germany 10117

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Judith Bellmann-Strobl, MD

CONTACT

+49 30 450 540258; judith.bellmann-strobl@charite.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior physician

Model Details: Prospective randomized, placebo-controlled, double-blind, multicenter, phase 2b trial.

Study Record Dates

• First Submitted: July 21, 2026
• First Posted: July 24, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: July 24, 2026

Record last verified: 2026-07

Locations

DE (1)