Home › Research › Treatments
XPro1595, a Selective Soluble TNF Neutralizer, in Early Alzheimer’s Disease with Inflammation (ADi): Results from the Phase 2 MINDFuL Trial
Jaeger J, Staats KA, Barnum S, Pope P, Kingery L, Buitendyk M, Cohen S, Tansey MG et al.. medRxiv, 2025-09-27
Topic: Drug trials: efficacy and safety
Results Of 206 randomized participants, 200 comprised the modified intent-to-treat (mITT) population and 100 comprised the ADi population. In the mITT analysis, no significant difference was observed in the EMACC (p=0.672). These results were consistent with biomarker changes that favored XPro1595, as plasma pTau217 (d = -0.18) and GFAP (d = -0.19) were attenuated in the ADi population. Conclusions While XPro1595 did not meet the primary endpoint in the overall population, participants with biologically-defined AD and high inflammatory burden demonstrated consistent trends toward cognitive benefit and neuropsychiatric improvement. The complete absence of ARIA distinguishes XPro1595 from amyloid-targeting therapies and supports its potential for use in combination strategies and potentially for those at a higher risk of ARIA. These findings support selective TNF inhibition as a promising therapeutic approach for persons with AD and elevated inflammatory burden.
Key findings
- Results Of 206 randomized participants, 200 comprised the modified intent-to-treat (mITT) population and 100 comprised the ADi population.
- In the mITT analysis, no significant difference was observed in the EMACC (p=0.672).
- These results were consistent with biomarker changes that favored XPro1595, as plasma pTau217 (d = -0.18) and GFAP (d = -0.19) were attenuated in the ADi population.
- Conclusions While XPro1595 did not meet the primary endpoint in the overall population, participants with biologically-defined AD and high inflammatory burden demonstrated consistent trends toward cognitive benefit and neuropsychiatric improvement.
- The complete absence of ARIA distinguishes XPro1595 from amyloid-targeting therapies and supports its potential for use in combination strategies and potentially for those at a higher risk of ARIA.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Study designclinical trial
- Evidence strengthHigh
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 26 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 16 of the 62 points we could judge it on, which is 26 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 16 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 16 of the 62 points we could judge it on is 26 out of 100. |
| Total | 26 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Jaeger, J., Staats, K. A., Barnum, S., Pope, P., Kingery, L., Buitendyk, M., et al. (2025). XPro1595, a Selective Soluble TNF Neutralizer, in Early Alzheimer’s Disease with Inflammation (ADi): Results from the Phase 2 MINDFuL Trial. medRxiv. https://doi.org/10.1101/2025.09.24.25336496
Vancouver
Jaeger J, Staats KA, Barnum S, Pope P, Kingery L, Buitendyk M, et al. XPro1595, a Selective Soluble TNF Neutralizer, in Early Alzheimer’s Disease with Inflammation (ADi): Results from the Phase 2 MINDFuL Trial. medRxiv. 2025. doi:10.1101/2025.09.24.25336496.
BibTeX
@article{jaeger2025-377d6a5b,
author = {Jaeger, J. and Staats, K. A. and Barnum, S. and Pope, P. and Kingery, L. and Buitendyk, M. and Cohen, S. and Tansey, M. G. and others},
title = {{XPro1595, a Selective Soluble TNF Neutralizer, in Early Alzheimer’s Disease with Inflammation (ADi): Results from the Phase 2 MINDFuL Trial}},
journal = {medRxiv},
year = {2025},
doi = {10.1101/2025.09.24.25336496},
url = {https://doi.org/10.1101/2025.09.24.25336496}
}
Related studies in Treatments
Also tagged “aducanumab”
332 studies in the library carry the topic tag “aducanumab”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 332 tagged studies.