Autoimmunity and Immunomodulation
1 Charit'{e Immunoadsorption Trial (IA-PACS-CFS)}
Principal Investigator:: Carmen Scheibenbogen, MD, Professor of Immunology
Institution:: Charité – Universitätsmedizin Berlin, Charité Fatigue Centrum, Germany
Contact/URL:: https://cfc.charite.de/en/clinical_research/nksg/trial_ia_pacs_cfs
Registry ID:: NCT05710770
Funder:: Institutional and ME/CFS Research Foundation
Status:: Completed (October 2025); results pending
Phase:: Double-blind, sham-controlled RCT (2:1 allocation)
Cohort:: 66 ME/CFS patients (post-COVID and other post-infectious) with elevated \(\beta_2\)-adrenergic receptor autoantibodies
Mechanism/Focus:: Five immunoadsorption sessions over 10 days to remove pathogenic autoantibodies targeting G-protein coupled receptors (GPCRs), compared with sham treatment. Prior open-label cohort (\(n=20\)) showed clinical improvement.
Primary Outcomes:: Clinical improvement at 3 months (Chalder Fatigue Scale); autoantibody levels; 6-month follow-up
Estimated Completion:: RCT completed October 2025; results pending
Timeline:: Open-label cohort 2022–2023 (published January 2025); double-blind RCT completed October 2025; protocol published (Preßler et al. 2024)
Publication Medium:: Open-label results in peer-reviewed journal (2025); RCT results expected in high-impact immunology journal
Document Relevance:: Ch. 7 (immune dysfunction—autoantibodies), Ch. 10 (autonomic dysfunction), Ch. 19 (integrative approaches)
The Charité immunoadsorption programme is the most advanced clinical investigation of the autoantibody hypothesis in ME/CFS. Scheibenbogen’s group has systematically built from case reports through an open-label cohort to a sham-controlled RCT—the methodological progression needed to establish causality. The requirement for elevated \(\beta_2\)-adrenergic receptor autoantibodies as an inclusion criterion represents a biomarker-stratified trial design, testing both the treatment and the underlying autoimmune mechanism simultaneously. A new 2026-funded neuroimaging substudy will assess whether thalamocortical hyperconnectivity normalises after immunoadsorption, linking peripheral autoimmunity to central nervous system changes.
2 EXTINCT Trial (Hannover Medical School)
Principal Investigator:: Hannover Medical School investigators
Institution:: Hannover Medical School, Germany
Contact/URL:: https://clinicaltrials.gov/study/NCT05954325
Registry ID:: NCT05954325
Funder:: Not publicly disclosed
Status:: Completed (September 2025); results pending
Phase:: Double-blind, sham-controlled RCT
Cohort:: 63 ME/CFS patients
Mechanism/Focus:: Five immunoadsorption sessions within 14 days vs. sham procedure. First independent-institution (non-Charité) sham-controlled RCT of immunoadsorption in ME/CFS.
Primary Outcomes:: Chalder Fatigue Scale at 12 weeks
Estimated Completion:: Completed September 2025; publication pending
Timeline:: Enrolment started August 2023; completed September 2025
Publication Medium:: Not yet announced
Document Relevance:: Ch. 7 (immune dysfunction), Ch. 14b (autoimmune hypothesis), Ch. 21 (clinical trials)
The EXTINCT trial is the first sham-controlled immunoadsorption RCT conducted independently of the Charité group. Together with IA-PACS-CFS (Section Autoimmunity and Immunomodulation), these two completed RCTs will provide the definitive test of whether immunoadsorption efficacy exceeds placebo in ME/CFS. Independent replication is critical given that all prior positive results originated from a single research group.
3 IMPACT Trial (Memory B-Cell Dynamics)
Principal Investigator:: Charité Fatigue Centrum investigators
Institution:: Charité – Universitätsmedizin Berlin, Germany
Contact/URL:: https://clinicaltrials.gov/study/NCT07529197
Registry ID:: NCT07529197
Funder:: Institutional (Charité)
Status:: Recruiting (since March 2026)
Phase:: Non-interventional prospective observational
Cohort:: 50 ME/CFS patients undergoing immunoadsorption
Mechanism/Focus:: Five outpatient IA sessions on days 1, 2, 4, 6, and 8. Primary novelty: systematic measurement of memory B-cell changes before and after IA—addressing the mechanistic question of why some patients relapse (memory B-cell repopulation and re-synthesis of autoantibodies).
Primary Outcomes:: SF-36 Physical Function at 8 weeks; memory B-cell dynamics
Estimated Completion:: Not yet announced
Timeline:: Recruiting since March 2026; outpatient design (first non-inpatient IA protocol)
Publication Medium:: Not yet announced
Document Relevance:: Ch. 7 (immune dysfunction), Ch. 14b (autoimmune hypothesis—plasma cell sanctuary)
The IMPACT trial is the first study to systematically investigate memory B-cell dynamics after immunoadsorption. This is mechanistically critical: if relapse after IA is driven by memory B-cell repopulation and re-differentiation into autoantibody-secreting plasma cells, then combining IA with B-cell depletion (rituximab) or plasma cell depletion (daratumumab) could prevent relapse. The outpatient design also represents a practical advance over the prior inpatient protocols.
4 BC007 (Rovunaptabin) Phase II Trials
Principal Investigator:: Multiple (industry-sponsored)
Institution:: Berlin Cures GmbH, Germany (multi-site)
Contact/URL:: https://clinicaltrials.gov/study/NCT05911009
Registry ID:: NCT05911009 (Phase II, \(n=114\)); earlier Phase IIa (\(n=29\))
Funder:: Berlin Cures GmbH (industry)
Status:: Phase II completed/in analysis
Phase:: Phase IIa (crossover, \(n=29\)) and Phase II (\(n=114\))
Cohort:: Post-COVID syndrome patients with functional GPCR autoantibodies and predominant fatigue
Mechanism/Focus:: Rovunaptabin (BC007) is an aptamer that neutralises functional autoantibodies against GPCRs. Unlike immunoadsorption (which removes all immunoglobulins non-selectively), BC007 targets pathogenic autoantibodies specifically.
Primary Outcomes:: Fatigue severity; autoantibody neutralisation; safety
Estimated Completion:: Results expected 2026
Timeline:: Phase IIa enrolled 29 patients; Phase II enrolled 114 patients; analysis ongoing
Publication Medium:: Not yet announced; industry-sponsored trials typically target high-impact journals
Document Relevance:: Ch. 7 (immune dysfunction—autoantibodies), Ch. 25 (translational findings)
BC007 and immunoadsorption represent complementary approaches to the same autoantibody hypothesis: immunoadsorption removes antibodies broadly, while BC007 neutralises specific pathogenic autoantibodies in situ. The Phase II trial (\(n=114\)) is the largest RCT testing autoantibody-targeted therapy in post-infectious fatigue conditions. Positive results would validate the functional GPCR autoantibody hypothesis and open a pharmacological treatment pathway. However, the trials enrolled post-COVID patients specifically; extension to non-COVID ME/CFS cohorts will be needed.
5 ResetME Trial (Daratumumab)
Principal Investigator:: Øystein Flüge and Olav Mella
Institution:: Haukeland University Hospital, Bergen, Norway (with Oslo University Hospital)
Contact/URL:: EudraCT / EU Clinical Trials Register
Registry ID:: European registry (no NCT number)
Funder:: ME Fund Norway; institutional
Status:: Recruiting (opened June 2025)
Phase:: Phase II, randomised, double-blind, placebo-controlled (2:1 ratio)
Cohort:: 66 participants; moderate-to-severe ME/CFS (CCC criteria), minimum 2-year disease duration
Mechanism/Focus:: Daratumumab is an anti-CD38 monoclonal antibody that depletes plasma cells, causing transient reduction of pathogenic autoantibodies (including anti-adrenergic and anti-cholinergic receptor antibodies). Follow-on from the open-label KTS9 pilot (\(n=10\), EudraCT 2022-000281-18), in which 6/10 patients showed marked improvement and mean SF-36 Physical Function rose from 25.9 to 55.0.
Primary Outcomes:: Symptom reduction (SF-36 Physical Function); safety
Estimated Completion:: \(\sim\) 2027 (72-week total participation)
Timeline:: 26-week treatment period, 72-week follow-up from June 2025 start
Publication Medium:: Not yet announced; pilot published in Frontiers in Medicine, June 2025
Document Relevance:: Ch. 7 (immune dysfunction—autoantibodies), Ch. 10 (adrenergic receptor autoantibodies), Ch. 19 (integrative approaches)
ResetME is among the highest-priority ongoing ME/CFS trials. Flüge and Mella are the same group that conducted the rituximab trials; daratumumab targets plasma cells more selectively via CD38. Unlike rituximab (which depletes CD20+ B cells), daratumumab directly reduces the antibody-secreting plasma cells hypothesised to produce pathogenic autoantibodies. The pilot response rate (60%, with near-doubling of physical function scores) is among the strongest signals in ME/CFS treatment research. If the RCT replicates these findings, it would establish the first disease-modifying treatment for an autoimmune subset of ME/CFS. Combined with BC007 (Section Autoimmunity and Immunomodulation) and immunoadsorption (Section Autoimmunity and Immunomodulation), this trial represents the third independent approach to the autoantibody hypothesis.