CompletedPhase 1Results posted

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease

A Randomized, Double-Blind, Placebo-Controlled Study, Followed by an Open-Label Extension, to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 814907 in Patients With Mild Alzheimer's Disease

Lead sponsor

Ionis Pharmaceuticals, Inc.

Asset

IONIS MAPTRx

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criterion

•Age 50-74

Primary endpoints

•Part 1•Part 2

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2016-002713-22

Org study IDISIS 814907-CS1

NCT IDNCT03186989

Secondary IDNL60032.000.16CCMO

Timeline

Milestones

Study first posted2017-06-14actual

Study start2017-10-12actual

Primary completion2022-05-12actual

Study completion2022-05-12actual

Last update posted2025-04-08actual

Results first posted2025-04-08actual

Assets

Drug assets

IONIS MAPTRx

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age74 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

for Part 1:

•Males or females aged 50-74 years, inclusive, at the time of informed consent

•Diagnosed with mild Alzheimers disease, including CSF biomarkers consistent with this diagnosis

•Body Mass Index BMI ≥ 18 and ≤ 35 kg/m2 and total body weight > 50 kg (110 lbs)

•Able and willing to meet all study requirements, including toleration for MRI scans, blood draws and lumbar punctures, travel to Study Center and participation in all procedures and measurements at study visits

•Have a trial partner who is reliable, competent and at least 18 years of age, is willing to accompany the patient to select trial visits and to be available to the Study Center by phone if needed

•Reside within 4 hours travel of the Study Center

Exclusion criteria

for Part 1:

•Treatment with another Study Drug, biological agent, or device within one-month of Screening or 5 half-lives of investigational agent, whichever is longer

•Clinically significant medical condition which would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study

•Use of a disallowed CNS-active or antipsychotic medication within 4 weeks prior to Screening punctures

Inclusion Criteria for Part 2:

•Must have completed the Treatment Evaluation and Post-Treatment Periods in Part 1

Exclusion Criteria for Part 2 (only applicable to participants in Cohorts A and B, as participants from Cohorts C and D will seamlessly transition to Part 2):

•Treatment with another Study Drug, biological agent, or device within one-month of Screening or 5 half-lives of investigational agent, whichever is longer

•Clinically significant medical condition which would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study

•Use of a disallowed CNS-active or antipsychotic medication within 4 weeks prior to Screening punctures

Endpoints (14)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Fluid / digital biomarkers

2 endpoints

Secondary/protocol endpoint

CSF Trough Concentration of ISIS 814907

Time frame:Pre dose on Day 85 in Part 1 and Day 337 in Part 2

concentration, descriptive

Secondary/registry result

CSF Trough Concentration of ISIS 814907

Time frame:Pre dose on Day 85 in Part 1 and Day 337 in Part 2

concentration, descriptive

Posted result

Group	Value (mean), nanogram per millilitre (ng/mL)	Standard deviation
Part 1: Cohort A: ISIS 814907 10 mgn=6 Participants	5.56	2.12
Part 1: Cohort B: ISIS 814907 30 mgn=6 Participants	9.77	3.46
Part 1: Cohort C: ISIS 814907 60 mgn=9 Participants	9.79	3.42
Part 1: Cohort D: ISIS 814907 115 mgn=12 Participants	3.26	1.24
Part 2: Cohort A + ISIS 814907 60 mgn=2 Participants	5.96	NA
Part 2: Cohort B + ISIS 814907 60 mgn=5 Participants	8.22	2.03
Part 2: Cohort C + ISIS 814907 60 mgn=9 Participants	6.61	2.89
Part 2: Cohort D + ISIS 814907 115 mgn=11 Participants	7.82	2.52

Safety / tolerability / PK

12 endpoints

Primary/protocol endpoint

Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907

Time frame:From first dose of study drug up to Week 37 in Part 1

event count, event

Primary/protocol endpoint

Part 2: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907

Time frame:From first dose of study drug up to Week 64 in Part 2

event count, event

Primary/registry result

Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907

Time frame:From first dose of study drug up to Week 37 in Part 1

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Part 1: Cohort A: ISIS 814907 10 mgMildn=6 Participants	3	-
Moderaten=6 Participants	0	-
Severen=6 Participants	0	-
Part 1: Cohort B: ISIS 814907 30 mgMildn=6 Participants	0	-
Moderaten=6 Participants	1	-
Severen=6 Participants	0	-
Part 1: Cohort C: ISIS 814907 60 mgMildn=9 Participants	5	-
Moderaten=9 Participants	1	-
Severen=9 Participants	0	-
Part 1: Cohort D: ISIS 814907 115 mgMildn=13 Participants	4	-
Moderaten=13 Participants	1	-
Severen=13 Participants	0	-
Part 1: Pooled PlaceboMildn=12 Participants	0	-
Moderaten=12 Participants	0	-
Severen=12 Participants	0	-

Primary/registry result

Part 2: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907

Time frame:From first dose of study drug up to Week 64 in Part 2

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mgMildn=4 Participants	1	-
Moderaten=4 Participants	0	-
Severen=4 Participants	0	-
Part 2: Late Start Cohort D + ISIS 814907 115 mgMildn=4 Participants	0	-
Moderaten=4 Participants	2	-
Severen=4 Participants	0	-
Part 2: Early Start Cohort A + ISIS 814907 60 mgMildn=3 Participants	1	-
Moderaten=3 Participants	1	-
Severen=3 Participants	0	-
Part 2: Early Start Cohort B + ISIS 814907 60 mgMildn=5 Participants	1	-
Moderaten=5 Participants	1	-
Severen=5 Participants	0	-
Part 2: Early Start Cohort C + ISIS 814907 60 mgMildn=7 Participants	0	-
Moderaten=7 Participants	1	-
Severen=7 Participants	0	-
Part 2: Early Start Cohort D + ISIS 814907 115 mgMildn=10 Participants	2	-
Moderaten=10 Participants	3	-
Severen=10 Participants	1	-

Secondary/protocol endpoint

Maximum Observed Drug Concentration (Cmax) of ISIS 814907 in Plasma

Time frame:Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-intrathecal (IT) bolus injection on Day 85 in Part 1 and on Day 337 in Part 2

concentration, descriptive

Secondary/protocol endpoint

Time Taken to Reach Maximal Concentration (Tmax) of ISIS 814907 in Plasma

Time frame:Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2

concentration, descriptive

Secondary/protocol endpoint

Terminal Elimination Half-life (t1/2λz) of ISIS 814907 in Plasma

Time frame:Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2

concentration, descriptive

Secondary/protocol endpoint

Areas Under the Plasma Concentration-time Curve From Zero Time (Predose) to 24 Hours After the IT Administration (AUC0-24h) of ISIS 814907

Time frame:Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2

concentration, descriptive

Secondary/registry result

Maximum Observed Drug Concentration (Cmax) of ISIS 814907 in Plasma

Time frame:Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-intrathecal (IT) bolus injection on Day 85 in Part 1 and on Day 337 in Part 2

concentration, descriptive

Posted result

Group	Value (geometric_mean), ng/mL	Geometric coefficient of variation
Part 1: Cohort A: ISIS 814907 10 mgn=6 Participants	65.4	203
Part 1: Cohort B: ISIS 814907 30 mgn=6 Participants	285	50.5
Part 1: Cohort C: ISIS 814907 60 mgn=9 Participants	542	148
Part 1: Cohort D: ISIS 814907 115 mgn=13 Participants	830	879
Part 2: Cohort A + ISIS 814907 60 mgn=2 Participants	840	NA
Part 2: Cohort B + ISIS 814907 60 mgn=5 Participants	323	56.6
Part 2: Cohort C + ISIS 814907 60 mgn=9 Participants	524	90.2
Part 2: Cohort D + ISIS 814907 115 mgn=12 Participants	1011	130

Secondary/registry result

Time Taken to Reach Maximal Concentration (Tmax) of ISIS 814907 in Plasma

Time frame:Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2

concentration, descriptive

Posted result

Group	Value (median), hours	Reported bounds
Part 1: Cohort A: ISIS 814907 10 mgn=6 Participants	3.13	-1.02 - 24.7
Part 1: Cohort B: ISIS 814907 30 mgn=6 Participants	4.00	-3.02 - 5.00
Part 1: Cohort C: ISIS 814907 60 mgn=9 Participants	4.02	-2.00 - 24.2
Part 1: Cohort D: ISIS 814907 115 mgn=13 Participants	3.38	-1.02 - 338
Part 2: Cohort A + ISIS 814907 60 mgn=2 Participants	2.05	-1.02 - 3.08
Part 2: Cohort B + ISIS 814907 60 mgn=5 Participants	4.02	-3.02 - 5.07
Part 2: Cohort C + ISIS 814907 60 mgn=9 Participants	4.15	-2.02 - 24.3
Part 2: Cohort D + ISIS 814907 115 mgn=12 Participants	4.03	-0.500 - 23.5

Secondary/registry result

Terminal Elimination Half-life (t1/2λz) of ISIS 814907 in Plasma

Time frame:Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2

concentration, descriptive

Posted result

Group	Value (geometric_mean), days	Geometric coefficient of variation
Part 1: Cohort A: ISIS 814907 10 mgn=6 Participants	19.4	62.7
Part 1: Cohort B: ISIS 814907 30 mgn=6 Participants	38.0	23.1
Part 1: Cohort C: ISIS 814907 60 mgn=9 Participants	34.8	22.6
Part 1: Cohort D: ISIS 814907 115 mgn=13 Participants	42.5	16.1
Part 2: Cohort A + ISIS 814907 60 mgn=2 Participants	10.7	NA
Part 2: Cohort B + ISIS 814907 60 mgn=5 Participants	10.3	8.99
Part 2: Cohort C + ISIS 814907 60 mgn=9 Participants	10.6	16.3
Part 2: Cohort D + ISIS 814907 115 mgn=12 Participants	13.8	54.0

Secondary/registry result

Areas Under the Plasma Concentration-time Curve From Zero Time (Predose) to 24 Hours After the IT Administration (AUC0-24h) of ISIS 814907

Time frame:Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2

concentration, descriptive

Posted result

Group	Value (geometric_mean), nanogramhours per millilitre (ngh/mL)	Geometric coefficient of variation
Part 1: Cohort A: ISIS 814907 10 mgn=6 Participants	679	119
Part 1: Cohort B: ISIS 814907 30 mgn=6 Participants	3638	36.0
Part 1: Cohort C: ISIS 814907 60 mgn=9 Participants	6143	92.4
Part 1: Cohort D: ISIS 814907 115 mgn=13 Participants	7120	3066
Part 2: Cohort A + ISIS 814907 60 mgn=2 Participants	10523	NA
Part 2: Cohort B + ISIS 814907 60 mgn=5 Participants	5176	44.5
Part 2: Cohort C + ISIS 814907 60 mgn=9 Participants	6396	68.7
Part 2: Cohort D + ISIS 814907 115 mgn=12 Participants	12542	50.2

Publications (4)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.