NCT03919162: VIVA-MIND

A Trial to Evaluate the Efficacy and Safety of PQ912 in Patients With Early AD

Terminated Phase 2 Results posted Last updated 12 December 2025

What this trial tests

Phase 2 trial testing PQ912 in Alzheimer Disease in 112 participants. Terminated before completion.

Timeline

15 November 2021

Primary endpoint
12 July 2024

12 August 2024

Quick facts

Lead sponsor	Vivoryon Therapeutics N.V.
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	112
Start date	15 November 2021
Primary completion	12 July 2024
Estimated completion	12 August 2024
Sites	22 locations across United States

Drugs / interventions tested

• PQ912
• Placebo

Conditions studied

• Alzheimer Disease — all drugs for Alzheimer Disease →

Sponsor

Vivoryon Therapeutics N.V. — full company profile →

Who can join

Adults 50 to 89, any sex, with Alzheimer Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 2A: Number of Participants With Any Adverse Event of Special Interest (AESI) Primary · From first dose to completion of 8 weeks on the full dose (Week 16)

The proportion of participants, who experience any AESI during the safety evaluation period, which is from first dose to completion of 8 weeks at the full originally assigned dose. Per protocol, if the first cohort (Cohort A) does not meet the pre-specified Pocock safety stopping boundary within the active arm, that dose will be selected as safe. The dose selected as safe will be the dose carried forward for all participants in the active arm for the remainder of the study. The Pocock boundary is only valid until dose selection. If a higher dose is selected as safe, assignment to lower doses w

Group	Value	95% CI
PQ912	1
Placebo	2

Phase 2A: Median Estimated Target Occupancy (TO) of PQ912 in Cerebrospinal Fluid (CSF) at Week 24 Primary · Week 24, pre-dose (trough level) and 2-3h post-dose

The pharmacokinetics (PK) endpoints in Phase 2A are the derived median values of PQ912 levels in plasma and the corresponding calculated target occupancy (TO) in CSF, following at least 8 weeks of treatment at the dose level being tested. TO in CSF was estimated from plasma PQ912 concentrations.

Week 24 (Visit 7) - pre-dose

Group	Value	95% CI
PQ912	55.3	0.0 – 86.4

Week 24 (Visit 7) - 2-3h post-dose

Group	Value	95% CI
PQ912	94.3	31.6 – 97.7

Phase 2A: Median Plasma Concentrations of PQ912 at Week 24 Primary · Week 24, pre-dose (trough level) and 2-3h post-dose

The pharmacokinetics (PK) endpoints in Phase 2A are the derived median values of PQ912 levels in plasma and the corresponding calculated target occupancy (TO) in CSF, following at least 8 weeks of treatment at the dose level being tested. Blood samples were obtained and PQ912 plasma concentrations were determined using a validated high-pressure liquid chromatography hyphenated with tandem mass spectrometry (LC-MS/MS) method.

Week 24 (Visit 7) - pre-dose

Group	Value	95% CI
PQ912	208.0	0.0 – 1070.0

Week 24 (Visit 7) - 2-3h post-dose

Group	Value	95% CI
PQ912	2790.0	77.7 – 7210.0

Phase 2A: Change From Baseline in Alzheimer's Disease Neuroimaging Initiative (ADNI) Battery Composite (ABC) Score Primary · 24 weeks

The within-participant change from baseline in the composite mean of standardized scores from a set of ADNI neuropsychological test measures, the ADNI Battery Composite (ABC, 9-item). The ABC score was calculated from the following 9 measures from the ADNI-1 Neuropsychological Test Battery: Auditory Verbal Learning Test (AVLT)-Immediate Recall, AVLT-Delayed Recall, Number Span Forward, Number Span Backward, Category Fluency, Trail Making Test A, Trail Making Test B, Digit Symbol Substitution, Boston Naming Test. Standardized scores (Z-scores) were calculated using the overall mean and standar

Group	Value	95% CI
PQ912	-0.156	± 0.036
Placebo	-0.214	± 0.039

Phase 2A: Change From Baseline in Quantitative Electroencephalogram (qEEG) Primary · 24 weeks

The within-participant change from baseline of global relative theta wave power (4-8 Hz) in qEEG. qEEG was used to assess resting-state brain activity, including global relative theta power (4-8 Hz), based on spectral analysis of signals from 21 electrode positions. Higher theta power indicates greater impairment.

Group	Value	95% CI
PQ912	0.01749	± 0.00649
Placebo	0.02275	± 0.00619

Phase 2B: Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score Primary · 72 weeks

The within-participant change from baseline in CDR-SB scores. The CDR-SB is a composite rating of cognition and everyday function which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview three cognitive domains (memory, orientation, and judgement/problem solving) and three everyday functional domains (community affairs, home and hobbies, and personal care). Level of impairment in each of the six domains is rated from none (score=0) to severe (score=3). The six domain scores are then summed to create the CDR-SB. Range: 0-18; hig

Group	Value	95% CI
PQ912	1.63	± 0.36
Placebo	1.68	± 0.34

Phase 2B: Key Secondary Efficacy: Change From Baseline in Cognitive Functional Composite-2 (CFC2) Score, a Cognitive Functional Composite Secondary · 72 weeks

The within-participant change from baseline in CFC2 scores. The CFC2 is a novel composite outcome measure of cognition and everyday function that has been derived from measures used in Alzheimer's Disease Neuroimaging Initiative (ADNI) and optimized for detecting change in early Alzheimer's disease (doi.org/10.1016/j.jalz.2012.05.2187). CFC2 is comprised of selected subtests from the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) (Word Recall, Delayed Word Recall, and Orientation), Clinical Dementia Rating (CDR) sum of the Cognitive Boxes (Memory, Orientation, Judgement, an

Group	Value	95% CI
PQ912	-6.694	± 1.613
Placebo	-7.664	± 1.512

Phase 2B: Change From Baseline in Alzheimer's Disease Neuroimaging Initiative (ADNI) Battery Composite (ABC, 9-item) Score Secondary · 72 weeks

The within-participant change from baseline in the composite sum of standardized scores from a set of ADNI neuropsychological test measures, the ADNI Battery Composite (ABC, 9-item). The ABC score is calculated from the following 9 measures from the ADNI-1 Neuropsychological Test Battery: Auditory Verbal Learning Test (AVLT)-Immediate Recall, AVLT-Delayed Recall, Number Span Forward, Number Span Backward, Category Fluency, Trail Making Test A, Trail Making Test B, Digit Symbol Substitution, Boston Naming Test. Standardized scores (Z-scores) were calculated using the overall mean and standard d

Group	Value	95% CI
PQ912	-0.278	± 0.078
Placebo	-0.378	± 0.069

Phase 2B: Change From Baseline in Quantitative Electroencephalogram (qEEG) Secondary · 72 weeks

The within-participant change from baseline of global relative theta wave power (4-8 Hz) in qEEG. qEEG was used to assess resting-state brain activity, including global relative theta power (4-8 Hz), based on spectral analysis of signals from 21 electrode positions. Higher theta power indicates greater impairment.

Group	Value	95% CI
PQ912	-0.01123	± 0.01474
Placebo	0.01734	± 0.01291

Phase 2B: Change From Baseline in Functional Activities Questionnaire (FAQ) Secondary · 72 weeks

The within-participant change from baseline in FAQ.The FAQ is a validated 10-item questionnaire, completed as a structured interview with the study partner, which rates the study participant's ability to carry out ten complex activities of daily living (doi.org/10.1093/geronj/37.3.323). Each item is rated on a scale from 0 (no impairment) to 3 (dependent). Scores are summed across items to provide a total score. Range: 0 to 30; higher scores indicate greater impairment.

Group	Value	95% CI
PQ912	4.36	± 1.35
Placebo	4.97	± 1.23

Phase 2B: Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog-13) Secondary · 72 weeks

The within-participant change from baseline in ADAS-Cog-13. The ADAS-Cog-13 is a structured scale that evaluates memory (immediate and delayed word recall; immediate word recognition), receptive and expressive language, orientation, ideational praxis (preparing a letter for mailing), constructional praxis (copying figures), and attention (number cancellation). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions also are obtained. The ADAS-Cog total score is calculated by summing the scores of the 13 component subtests. Range: 0

Group	Value	95% CI
PQ912	6.377	± 1.627
Placebo	4.343	± 1.470

Phase 2B: Change From Baseline in Neuropsychiatric Inventory (NPI) Secondary · 72 weeks

The within-participant change from baseline in NPI. The NPI is a well-validated, reliable, multi-item instrument to assess psychopathology in Alzheimer's disease dementia based on the results of an interview with the study partner. Frequency and severity of 12 neuropsychiatric symptoms are assessed. Range: 0 to 144; higher scores indicate greater impairment.

Group	Value	95% CI
PQ912	-0.14	± 1.80
Placebo	2.95	± 1.60

Adverse events — posted to ClinicalTrials.gov

Time frame: 76 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PQ912

Serious: 11/53 (21%)

Deaths: 2/53

Placebo

Serious: 6/56 (11%)

Deaths: 0/56

Serious adverse events (23 terms)

Reaction	System	PQ912	Placebo
Pneumonia	Infections and infestations	—	—
Metabolic encephalopathy	Nervous system disorders	—	—
Hemorrhage intracranial	Nervous system disorders	—	—
Syncope	Nervous system disorders	—	—
Transient ischaemic attack	Nervous system disorders	—	—
Sepsis	Infections and infestations	—	—
Clostridium difficile colitis	Infections and infestations	—	—
Bacterial sepsis	Infections and infestations	—	—
Staphylococcal infection	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Urinary tract infection bacterial	Infections and infestations	—	—
Urinary tract infection staphylococcal	Infections and infestations	—	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Adenocarcinoma pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Angina pectoris	Cardiac disorders	—	—
Sinus node dysfunction	Cardiac disorders	—	—
Gastric ulcer perforation	Gastrointestinal disorders	—	—
Adverse drug reaction	General disorders	—	—
Wound evisceration	Injury, poisoning and procedural complications	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Ovarian cyst	Reproductive system and breast disorders	—	—
Metastatic malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—

Other adverse events (15 terms — click to expand)

Reaction	System	PQ912	Placebo
Diarrhoea	Gastrointestinal disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
COVID-19	Infections and infestations	—	—
Dizziness	Nervous system disorders	—	—
Nasopharyingitis	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Nausea	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Skin laceration	Injury, poisoning and procedural complications	—	—
Contusion	Injury, poisoning and procedural complications	—	—
Skin abrasion	Injury, poisoning and procedural complications	—	—
Depression	Psychiatric disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Blood creatine phosphokinase increased	Investigations	—	—

Most-reported serious reactions: Pneumonia, Metabolic encephalopathy, Hemorrhage intracranial, Syncope, Transient ischaemic attack, Sepsis, Clostridium difficile colitis, Bacterial sepsis.

Data from ClinicalTrials.gov NCT03919162 adverse events section.

Sponsor's own description

This is a Phase 2A multi-center, randomized, double blind, placebo-controlled, parallel group study of varoglutamstat, with a stage gate to Phase 2B.

In Phase 2A there will be adaptive dosing evaluation of three dose levels with exposure to varoglutamstat or placebo for a minimum of 24 weeks, with preliminary evaluation of both cognitive function and pharmacodynamic changes on EEG spectral analysis in approximately 180 participants.

In the event that the stage gate for Phase 2B is reached, then Phase 2B will assesses efficacy and longer-term safety in a larger study group, i.e., 414.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.
   Zhang J, Zhang Y, Wang J, Xia Y, et al · · 2024 · cited 489× · PMID 39174535 · DOI 10.1038/s41392-024-01911-3
2. Alzheimer's disease drug development pipeline: 2022.
   Cummings J, Lee G, Nahed P, Kambar MEZN, et al · · 2022 · cited 369× · PMID 35516416 · DOI 10.1002/trc2.12295
3. Alzheimer's disease drug development pipeline: 2020.
   Cummings J, Lee G, Ritter A, Sabbagh M, et al · · 2020 · cited 350× · PMID 32695874 · DOI 10.1002/trc2.12050
4. Alzheimer's disease drug development pipeline: 2023.
   Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2023 · cited 326× · PMID 37251912 · DOI 10.1002/trc2.12385
5. Alzheimer's disease drug development pipeline: 2021.
   Cummings J, Lee G, Zhong K, Fonseca J, et al · · 2021 · cited 312× · PMID 34095440 · DOI 10.1002/trc2.12179
6. Pathological mechanisms and therapeutic strategies for Alzheimer's disease.
   Ju Y, Tam KY. · · 2022 · cited 260× · PMID 34380884 · DOI 10.4103/1673-5374.320970
7. Alzheimer's disease drug development pipeline: 2024.
   Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2024 · cited 209× · PMID 38659717 · DOI 10.1002/trc2.12465
8. Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update.
   Huang LK, Kuan YC, Lin HW, Hu CJ. · · 2023 · cited 165× · PMID 37784171 · DOI 10.1186/s12929-023-00976-6