Google Maps

NCT07724834

Overview

NCT ID: NCT07724834
Lead Sponsor: Charite University, Berlin, GermanyOTHER
Official Title: Prospective, Randomized, Double-blind, Placebo-controlled Phase 2b Trial Evaluating the Efficacy and Safety of the Anti-CD19 Monoclonal Antibody Inebilizumab Compared With Placebo in Patients With Post-acute Infection Syndromes Fulfilling ME/CFS Criteria (PIONEER)
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.

Status and Timeline

Status: Not yet recruiting
Last Update Posted: Jul 24, 2026Actual
Start Date: Dec 1, 2026Estimated
Primary Completion Date: Feb 1, 2029Estimated
Completion Date

Participation Criteria

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers?: No
Eligibility Criteria: Inclusion Criteria:

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

Detection of autoantibodies (elevated ß2R adrenergic AAB) prior to immunoadsorption or prior to inclusion to PIONEER

Pre-treatment with immunoadsorption in the immunoadsorption studies at least 6 months before study inclusion

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%)

Exclusion Criteria:

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

Participation in another clinical trial with a medical device or an investigational medicinal product within 3 Months or 5 half-lives (whichever is longer) before screening visit

Study Plan

Study Type: Interventional
Phase: Phase 2
Enrollment: 38Estimated
Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Quadruple

Contacts and Locations

Central Contacts: Judith Bellmann-Strobl, MDContact
judith.bellmann-strobl@charite.de

Similar Studies

Participant Group/Arms

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

PlaceboPlacebo 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