CompletedNCT03186989Updated Apr 8, 2025Results posted

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

A Phase 1 interventional study of IONIS MAPTRx and Placebo in Mild Alzheimer's Disease, sponsored by Ionis Pharmaceuticals, Inc.. Completed at 13 sites in 6 countries. Open to participants aged 50 Years to 74 Years. Per ClinicalTrials.gov, last updated 2025-04-08.

Sponsored by Ionis Pharmaceuticals, Inc. · Phase 1, Interventional, and Other

Phase: Phase 1
Study type: Interventional
Enrollment: 46
Allocation: Randomized
Ages: 50 Years to 74 Years
Sex: All

Study summary

The purpose of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS-MAPTRx in patients with Mild Alzheimer's Disease.

Read the detailed description

This was a randomized, double-blind, placebo-controlled study in 46 participants, followed by an Open-Label Extension. This study consisted of two parts:

Part 1: a randomized, double-blind, placebo-controlled multiple ascending dose period in participants with Mild Alzheimer's Disease, followed by Part 2: the open-label, long-term extension period.

Conditions studied

Mild Alzheimer's Disease

Browse trials for

Alzheimer Disease 3,678

Keywords

Mild Alzheimer's Disease
ISIS 814907
Memory Loss
Alzheimers
MAPT
Tau

In context

Alzheimer Disease

3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.

This study's enrollment of 46 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.

Browse Alzheimer Disease studies →

Lead sponsor

Ionis Pharmaceuticals, Inc. is the lead sponsor of 116 studies on the registry; 10 are open to participants now.

Of its 48 completed or terminated interventional studies of FDA-regulated products, 21 (44%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 50 Years to 74 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

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

Study design

Phase: Phase 1
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 46 participants (actual)

Study arms

Experimental
Part 1: Cohort A: ISIS 814907 10 mg
Participants received 10 milligrams (mg) ISIS 814907 diluted in 20 milliliters (mL) artificial cerebrospinal fluid (CSF), intrathecally, every four weeks (Q4W) on Days 1, 29, 57, and 85 in Part 1 of the study.
Drug: IONIS MAPTRx
Experimental
Part 1: Cohort B: ISIS 814907 30 mg
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
Drug: IONIS MAPTRx
Experimental
Part 1: Cohort C: ISIS 814907 60 mg
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
Drug: IONIS MAPTRx
Experimental
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, every 12 weeks (Q12W) on Days 1 and 85 in Part 1 of the study.
Drug: IONIS MAPTRx
Placebo comparator
Part 1: Pooled Placebo
Participants received 20 mL artificial CSF, intrathecally, as placebo on Days 1, 29, 57, and 85 for the 4-dose regimens, or on Days 1 and 85 for the 2-dose regimens in Part 1 of the study.
Other: Placebo
Experimental
Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg
Participants from MAD Cohorts A, B, C that were placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Experimental
Part 2: Late Start Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were placebo-treated, received 115 mg ISIS 814907 diluted up in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Experimental
Part 2: Early Start Cohort A + ISIS 814907 60 mg
Participants from MAD Cohort A that were ISIS 814907 10 mg -treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Experimental
Part 2: Early Start Cohort B + ISIS 814907 60 mg
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Experimental
Part 2: Early Start Cohort C + ISIS 814907 60 mg
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Experimental
Part 2: Early Start Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx

Interventions

DrugIONIS MAPTRx
IONIS MAPTRx injections.
Also known as: ISIS 814907
OtherPlacebo
Artificial CSF injections.

What researchers measure

Primary outcomes

Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.
Time frame: From first dose of study drug up to Week 37 in Part 1
Part 2: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.
Time frame: From first dose of study drug up to Week 64 in Part 2

Secondary outcomes

CSF Trough Concentration of ISIS 814907
Time frame: Pre dose on Day 85 in Part 1 and Day 337 in Part 2
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
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
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
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

Results

Posted Apr 8, 2025

Participant flow

The study was conducted at 12 investigative sites in the Germany, United Kingdom, the Netherlands, Sweden, Canada, and Finland from 23 August 2017 to 12 May 2022.

Part 1: MAD (Day 1 up to Week 36)

Participant flow — Part 1: MAD (Day 1 up to Week 36)
Milestone	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 1: Pooled Placebo
Started	6	6	9	13	12
Completed	6	6	8	12	11
Not completed	0	0	1	1	1
Withdrew: Voluntary withdrawal	0	0	1	1	1

Part 2: LTE (Week 37 to Week 101)

Participant flow — Part 2: LTE (Week 37 to Week 101)
Milestone	Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg	Part 2: Late Start Cohort D + ISIS 814907 115 mg	Part 2: Early Start Cohort A + ISIS 814907 60 mg	Part 2: Early Start Cohort B + ISIS 814907 60 mg	Part 2: Early Start Cohort C + ISIS 814907 60 mg	Part 2: Early Start Cohort D + ISIS 814907 115 mg
Started	4	4	3	5	7	10
Completed	2	2	3	4	7	10
Not completed	2	2	0	1	0	0
Withdrew: Voluntary withdrawal	1	0	0	0	0	0
Withdrew: Investigator judgement	0	1	0	0	0	0
Withdrew: Adverse event or serious adverse event (sae)	1	1	0	1	0	0

Outcome measures

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

An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.

Time frame:: From first dose of study drug up to Week 37 in Part 1
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
Participants	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg
Mild	3	0	5	4
Moderate	0	1	1	1
Severe	0	0	0	0

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

An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.

Time frame:: From first dose of study drug up to Week 64 in Part 2
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
Participants	Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg	Part 2: Late Start Cohort D + ISIS 814907 115 mg	Part 2: Early Start Cohort A + ISIS 814907 60 mg	Part 2: Early Start Cohort B + ISIS 814907 60 mg	Part 2: Early Start Cohort C + ISIS 814907 60 mg	Part 2: Early Start Cohort D + ISIS 814907 115 mg
Mild	1	0	1	1	0	2
Moderate	0	2	1	1	1	3
Severe	0	0	0	0	0	1

SecondaryCSF Trough Concentration of ISIS 814907

Time frame:: Pre dose on Day 85 in Part 1 and Day 337 in Part 2
Reported as:: Mean · nanogram per millilitre (ng/mL)

CSF Trough Concentration of ISIS 814907
nanogram per millilitre (ng/mL)	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 2: Cohort A + ISIS 814907 60 mg	Part 2: Cohort B + ISIS 814907 60 mg	Part 2: Cohort C + ISIS 814907 60 mg	Part 2: Cohort D + ISIS 814907 115 mg
CSF Trough Concentration of ISIS 814907	5.56 ± 2.12	9.77 ± 3.46	9.79 ± 3.42	3.26 ± 1.24	5.96 ± NA	8.22 ± 2.03	6.61 ± 2.89	7.82 ± 2.52

SecondaryMaximum 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
Reported as:: Geometric mean · ng/mL

Maximum Observed Drug Concentration (Cmax) of ISIS 814907 in Plasma
ng/mL	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 2: Cohort A + ISIS 814907 60 mg	Part 2: Cohort B + ISIS 814907 60 mg	Part 2: Cohort C + ISIS 814907 60 mg	Part 2: Cohort D + ISIS 814907 115 mg
Maximum Observed Drug Concentration (Cmax) of ISIS 814907 in Plasma	65.4 ± 203	285 ± 50.5	542 ± 148	830 ± 879	840 ± NA	323 ± 56.6	524 ± 90.2	1011 ± 130

SecondaryTime 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
Reported as:: Median · hours

Time Taken to Reach Maximal Concentration (Tmax) of ISIS 814907 in Plasma
hours	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 2: Cohort A + ISIS 814907 60 mg	Part 2: Cohort B + ISIS 814907 60 mg	Part 2: Cohort C + ISIS 814907 60 mg	Part 2: Cohort D + ISIS 814907 115 mg
Time Taken to Reach Maximal Concentration (Tmax) of ISIS 814907 in Plasma	3.13 (1.02 to 24.7)	4.00 (3.02 to 5.00)	4.02 (2.00 to 24.2)	3.38 (1.02 to 338)	2.05 (1.02 to 3.08)	4.02 (3.02 to 5.07)	4.15 (2.02 to 24.3)	4.03 (0.500 to 23.5)

SecondaryTerminal 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
Reported as:: Geometric mean · days

Terminal Elimination Half-life (t1/2λz) of ISIS 814907 in Plasma
days	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 2: Cohort A + ISIS 814907 60 mg	Part 2: Cohort B + ISIS 814907 60 mg	Part 2: Cohort C + ISIS 814907 60 mg	Part 2: Cohort D + ISIS 814907 115 mg
Terminal Elimination Half-life (t1/2λz) of ISIS 814907 in Plasma	19.4 ± 62.7	38.0 ± 23.1	34.8 ± 22.6	42.5 ± 16.1	10.7 ± NA	10.3 ± 8.99	10.6 ± 16.3	13.8 ± 54.0

SecondaryAreas 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
Reported as:: Geometric mean · nanogram*hours per millilitre (ng*h/mL)

Areas Under the Plasma Concentration-time Curve From Zero Time (Predose) to 24 Hours After the IT Administration (AUC0-24h) of ISIS 814907
nanogramhours per millilitre (ngh/mL)	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 2: Cohort A + ISIS 814907 60 mg	Part 2: Cohort B + ISIS 814907 60 mg	Part 2: Cohort C + ISIS 814907 60 mg	Part 2: Cohort D + ISIS 814907 115 mg
Areas Under the Plasma Concentration-time Curve From Zero Time (Predose) to 24 Hours After the IT Administration (AUC0-24h) of ISIS 814907	679 ± 119	3638 ± 36.0	6143 ± 92.4	7120 ± 3066	10523 ± NA	5176 ± 44.5	6396 ± 68.7	12542 ± 50.2

Adverse events

Collected over From first dose of study drug up to Week 37 in Part 1 and up to Week 64 in Part 2. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part 1: Cohort A: ISIS 814907 10 mg	0/6 (0%)	0/6 (0%)	6/6 (100%)
Part 1: Cohort B: ISIS 814907 30 mg	0/6 (0%)	0/6 (0%)	5/6 (83.3%)
Part 1: Cohort C: ISIS 814907 60 mg	0/9 (0%)	0/9 (0%)	9/9 (100%)
Part 1: Cohort D: ISIS 814907 115 mg	0/13 (0%)	0/13 (0%)	12/13 (92.3%)
Part 1: Pooled Placebo	0/12 (0%)	2/12 (16.7%)	9/12 (75%)
Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg	0/4 (0%)	1/4 (25%)	4/4 (100%)
Part 2: Late Start Cohort D + ISIS 814907 115 mg	0/4 (0%)	0/4 (0%)	3/4 (75%)
Part 2: Early Start Cohort A + ISIS 814907 60 mg	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
Part 2: Early Start Cohort B + ISIS 814907 60 mg	0/5 (0%)	1/5 (20%)	4/5 (80%)
Part 2: Early Start Cohort C + ISIS 814907 60 mg	0/7 (0%)	0/7 (0%)	7/7 (100%)
Part 2: Early Start Cohort D + ISIS 814907 115 mg	0/1 (0%)	1/10 (10%)	10/10 (100%)

Most frequent serious events

Most frequent serious events
Event	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 1: Pooled Placebo	Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg	Part 2: Late Start Cohort D + ISIS 814907 115 mg	Part 2: Early Start Cohort A + ISIS 814907 60 mg	Part 2: Early Start Cohort B + ISIS 814907 60 mg	Part 2: Early Start Cohort C + ISIS 814907 60 mg	Part 2: Early Start Cohort D + ISIS 814907 115 mg
Balance disorderNervous system disorders	0/6	0/6	0/9	0/13	0/12	0/4	0/4	1/3	0/5	0/7	0/10
AggressionPsychiatric disorders	0/6	0/6	0/9	0/13	0/12	1/4	0/4	0/3	0/5	0/7	0/10
ParanoiaPsychiatric disorders	0/6	0/6	0/9	0/13	0/12	1/4	0/4	0/3	0/5	0/7	0/10
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders	0/6	0/6	0/9	0/13	0/12	0/4	0/4	0/3	1/5	0/7	0/10
Lower respiratory tract infectionInfections and infestations	0/6	0/6	0/9	0/13	0/12	0/4	0/4	0/3	1/5	0/7	0/10
ParkinsonismNervous system disorders	0/6	0/6	0/9	0/13	0/12	0/4	0/4	0/3	0/5	0/7	1/10
Cerebrovascular accidentNervous system disorders	0/6	0/6	0/9	0/13	1/12	0/4	0/4	0/3	0/5	0/7	0/10
DiverticulitisInfections and infestations	0/6	0/6	0/9	0/13	1/12	0/4	0/4	0/3	0/5	0/7	0/10

Most frequent other events

Showing 10 of 141

Most frequent other events
Event	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 1: Pooled Placebo	Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg	Part 2: Late Start Cohort D + ISIS 814907 115 mg	Part 2: Early Start Cohort A + ISIS 814907 60 mg	Part 2: Early Start Cohort B + ISIS 814907 60 mg	Part 2: Early Start Cohort C + ISIS 814907 60 mg	Part 2: Early Start Cohort D + ISIS 814907 115 mg
Back painMusculoskeletal and connective tissue disorders	0/6	0/6	2/9	1/13	1/12	1/4	3/4	1/3	2/5	1/7	5/10
Post lumbar puncture syndromeInjury, poisoning and procedural complications	3/6	1/6	2/9	3/13	3/12	0/4	1/4	0/3	0/5	1/7	2/10
HeadacheNervous system disorders	2/6	3/6	3/9	2/13	3/12	1/4	0/4	1/3	1/5	1/7	4/10
Pain in extremityMusculoskeletal and connective tissue disorders	0/6	0/6	1/9	1/13	0/12	2/4	1/4	1/3	0/5	2/7	3/10
Procedural painInjury, poisoning and procedural complications	2/6	0/6	3/9	2/13	1/12	0/4	0/4	1/3	0/5	3/7	1/10
DizzinessNervous system disorders	0/6	1/6	2/9	0/13	1/12	0/4	0/4	0/3	1/5	3/7	1/10
FatigueGeneral disorders	1/6	0/6	1/9	1/13	0/12	0/4	0/4	1/3	0/5	0/7	3/10
Peripheral swellingGeneral disorders	0/6	0/6	0/9	0/13	0/12	0/4	0/4	1/3	0/5	0/7	0/10
Confusional statePsychiatric disorders	0/6	0/6	0/9	3/13	0/12	0/4	1/4	1/3	0/5	0/7	2/10
AnxietyPsychiatric disorders	0/6	0/6	0/9	1/13	0/12	0/4	0/4	1/3	0/5	0/7	2/10

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 1: Pooled Placebo	Total
Mean	63.5 ± 5.2	65.0 ± 6.1	65.6 ± 6.8	66.9 ± 6.3	66.3 ± 4.6	65.8 ± 5.7

Sex: Female, Male
Sex: Female, Male(Participants)	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 1: Pooled Placebo	Total
Female	2	4	5	6	6	23
Male	4	2	4	7	6	23

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 1: Pooled Placebo	Total
Hispanic or Latino	0	0	0	0	1	1
Not Hispanic or Latino	6	6	9	13	11	45
Unknown or Not Reported	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Part 1: Cohort A: ISIS 814907 10 mg	Part 1: Cohort B: ISIS 814907 30 mg	Part 1: Cohort C: ISIS 814907 60 mg	Part 1: Cohort D: ISIS 814907 115 mg	Part 1: Pooled Placebo	Total
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0
White	6	6	9	13	12	46
More than one race	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0

Study locations

13 sites

Montreal Neurological Hospital
Montréal, Canada
Clinical Research Services Turku CRST
Turku, Finland
St Josef Hospital
Bochum, Germany
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Bonn, 53127, Germany
MVZ Mittweida Gbr
Mittweida, Germany
Universittsklinikum Ulm
Ulm, Germany
VU University Medical Center
Amsterdam, 1081 HV, Netherlands
QPS Netherlands BV
Groningen, 9713 AG, Netherlands
Minnesmottagningen
Mölndal, Sweden
Karolinska University Hospital Huddinge
Stockholm, Sweden
Royal Liverpool University Hospital
Liverpool, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Sheffield Institute for Translational Neuroscience (SITraN)
Sheffield, United Kingdom

References and documents

Study documents

Protocol and statistical analysis plan · Apr 27, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 8, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03186989
Lead sponsor: Ionis Pharmaceuticals, Inc.
Responsible party: Sponsor
First posted: Jun 14, 2017
Start date: Oct 12, 2017
Primary completion: May 12, 2022
Completion: May 12, 2022
Results posted: Apr 8, 2025
Last update: Apr 8, 2025

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2025. You cannot join it, but the record below documents what was studied.

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Other studies from this sponsor

Ionis Pharmaceuticals, Inc.

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