What large ongoing randomized trials are testing neuromodulation (TMS/tACS) or anti‑tau antibodies in MCI and when will their results be reported?
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Executive summary
Large, randomized anti‑tau antibody trials enrolling people with mild cognitive impairment (MCI) are actively underway and have staggered completion dates through 2027–2028, while the reporting provided contains no clear evidence of large, ongoing randomized transcranial magnetic stimulation (TMS) or transcranial alternating current stimulation (tACS) trials in MCI; reporting gaps on neuromodulation trials limit firm conclusions [1] [2] [3] [4].
1. The anti‑tau trial landscape: who’s running large MCI studies and when results are expected
Several Phase 2 and Phase 2/3 anti‑tau antibody trials specifically include people with MCI due to Alzheimer’s disease (AD) or “early AD,” and their primary completion dates range from late 2026 through 2028: a Phase II study with a cognitive primary outcome (NCT05399888) is slated to run through December 2026 [3], Bristol‑Myers Squibb’s anti‑MTBR tau antibody BMS‑986446 (TargetTau‑1) is in multi‑site testing with trial activity expected to complete around 2027 and a UCSF listing shows a site ending March 2027 [2] [4], and the DIAN‑TU NexGen Phase 2/3 platform has finished enrollment of 197 participants with results expected in 2028 [1].
2. DIAN‑TU NexGen: a high‑profile tau antibody readout expected in 2028
The Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN‑TU) NexGen trial finished enrolling its cohort of 197 and is widely cited as a keystone anti‑tau readout, with results publicly anticipated in 2028 — a timeline that makes NexGen the single large, late‑stage anti‑tau readout on the near horizon [1].
3. BMS‑986446 / TargetTau‑1: multi‑site early‑AD testing with a 2027 finish window
BMS‑986446 (an anti‑MTBR tau antibody) has been fast‑tracked and is being tested in early AD/MCI populations under the TargetTau‑1 program; publicly reported schedules list an expected trial completion in 2027 and individual sites such as UCSF show study activity through March 2027 [2] [4].
4. Other ongoing anti‑tau trials: staggered phases and mixed histories
A number of other anti‑tau programs are in Phase 1–2 in MCI or early AD cohorts: BIIB092 (gosuranemab) ran a TANGO Phase 2 in MCI/early AD with an 18‑month monthly infusion plan and a multi‑year extension (development for some indications later halted), MK‑2214 had Phase‑I trials noted as scheduled to end in 2024, and multiple other antibodies (bepranemab, E2814, JNJ‑63733657/posdinemab, UCB0107 and others) are in active testing or early‑phase pipelines with trials in MCI populations and variable completion timelines [5] [6] [1] [7].
5. Clinical endpoints and what the readouts will mean
Most of these trials use biomarker‑heavy primary or coprimary endpoints—tau PET change or cognitive scales such as CDR‑Sum of Boxes or integrated AD Rating Scales—so readouts will report both target engagement (tau PET/CSF changes) and clinical impact over 12–36 months; for example TargetTau‑1 and several Phase 2 trials list tau PET and CDR‑SB among primary/secondary assessments [2] [5] [3].
6. Prior failures and interpretive caution
The anti‑tau field carries a history of several high‑profile negative trials—N‑terminal targeting antibodies like tilavonemab and gosuranemab failed to show clinical benefit in primary tauopathies and some programs were halted or redirected—so even positive biomarker changes may not translate into clinical benefit; trialists explicitly point to epitope selection and stage of disease as critical variables [7] [8] [9].
7. Neuromodulation (TMS/tACS) in MCI: absence of large randomized trials in the provided reporting
The materials supplied do not document any large, ongoing randomized TMS or tACS trials enrolling MCI populations with public completion dates; therefore no definitive list or readout schedule for neuromodulation trials can be provided from these sources, and this absence should be treated as a limitation of the available reporting rather than proof that such trials do not exist (none of [5]–[9] show large randomized TMS/tACS MCI trials).
8. What to watch and where the field may pivot
Immediate milestones to track are the December 2026 Phase II cognitive‑outcome trial readout (NCT05399888), the 2027 results window for BMS‑986446/TargetTau‑1 and the DIAN‑TU NexGen readout in 2028; beyond those dates, success will hinge on consistent biomarker reductions translating to durable clinical benefit and on whether newer antibodies target aggregation‑prone MTBR/tau epitopes rather than N‑terminal extracellular fragments, a strategic shift explicitly discussed in the field [3] [1] [2].