Mild Alzheimer's DiseasePhase 1NCT03186989
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease
A Phase 1 study testing IONIS MAPTRx in people with Mild Alzheimer's Disease, run by Ionis Pharmaceuticals, Inc. at 13 sites in 6 countries.
Trial 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 more about this study
- Who is it for?
- Ages 50 to 74 years
- Conditions the study is for
- Mild Alzheimer's Disease
- What is being tested?
- IONIS MAPTRx
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 13 sitesin 6 countries
- Study dates
- 12 Oct 2017to 12 May 2022
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
13 sites in 6 countries.
13 sites in 6 countries
Germany4 sites
St Josef Hospital
Bochum
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Bonn, 53127
MVZ Mittweida Gbr
Mittweida
Universittsklinikum Ulm
Ulm
United Kingdom3 sites
Royal Liverpool University Hospital
Liverpool
University College London Hospitals NHS Foundation Trust
London
Sheffield Institute for Translational Neuroscience (SITraN)
Sheffield
Netherlands2 sites
VU University Medical Center
Amsterdam, 1081 HV
QPS Netherlands BV
Groningen, 9713 AG
Sweden2 sites
Minnesmottagningen
Mölndal
Karolinska University Hospital Huddinge
Stockholm
About this study
Official title: 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
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
- Mild Alzheimer's Disease
- Being tested
- IONIS MAPTRx, Placebo
- Keywords
- Mild Alzheimer's Disease, ISIS 814907, Memory Loss, Alzheimers, MAPT, Tau
- Medical subject headings
- Memory Disorders, Pick Disease of the Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IONIS MAPTRxDrug
Also called ISIS 814907
IONIS MAPTRx injections.
PlaceboOther
Artificial CSF injections.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Cohort A: ISIS 814907 10 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
| Part 1: Cohort B: ISIS 814907 30 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
| Part 1: Cohort C: ISIS 814907 60 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
| Part 1: Cohort D: ISIS 814907 115 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
| Part 1: Pooled Placebo | Placebo comparator | 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. Receives: Other: Placebo |
| Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
| Part 2: Late Start Cohort D + ISIS 814907 115 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
| Part 2: Early Start Cohort A + ISIS 814907 60 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
| Part 2: Early Start Cohort B + ISIS 814907 60 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
| Part 2: Early Start Cohort C + ISIS 814907 60 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
| Part 2: Early Start Cohort D + ISIS 814907 115 mg | Experimental | 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. Receives: Drug: IONIS MAPTRx |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From first dose of study drug up to Week 64 in Part 2
Secondary outcomes (5)
CSF Trough Concentration of ISIS 814907
Measured: Pre dose on Day 85 in Part 1 and Day 337 in Part 2
Maximum Observed Drug Concentration (Cmax) of ISIS 814907 in Plasma
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study start12 Oct 2017
- Primary completion12 May 2022
- Study completion12 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mild Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03186989
- Sponsor's protocol ID
- ISIS 814907-CS1
- Other IDs
- NL60032.000.16, 2016-002713-22, 2016
- Status last verified
- Mar 2025
- First submitted
- 6 Jun 2017
- Last updated
- 8 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shulman M, Wu S, Ziogas N, Edwards A, Collins J, Lin L, Tien I, Curiale G, Li Y, Mummery C, Lane R, Junge C, Beaver J, Tian Y, Landen J, Bullain S, Gallagher D. Exploratory analyses of clinical outcomes from the BIIB080 phase 1b study in mild Alzheimer's disease. Nat Aging. 2026 Feb;6(2):445-453. doi: 10.1038/s43587-025-01031-9. Epub 2026 Feb 11.
PubMed 41673497Lane RM, Darreh-Shori T, Junge C, Li D, Yang Q, Edwards AL, Graham DL, Moore K, Mummery CJ. Onset of Alzheimer disease in apolipoprotein varepsilon4 carriers is earlier in butyrylcholinesterase K variant carriers. BMC Neurol. 2024 Apr 9;24(1):116. doi: 10.1186/s12883-024-03611-5.
PubMed 38594621Edwards AL, Collins JA, Junge C, Kordasiewicz H, Mignon L, Wu S, Li Y, Lin L, DuBois J, Hutchison RM, Ziogas N, Shulman M, Martarello L, Graham D, Lane R, Budd Haeberlein S, Beaver J. Exploratory Tau Biomarker Results From a Multiple Ascending-Dose Study of BIIB080 in Alzheimer Disease: A Randomized Clinical Trial. JAMA Neurol. 2023 Dec 1;80(12):1344-1352. doi: 10.1001/jamaneurol.2023.3861.
PubMed 37902726Mummery CJ, Borjesson-Hanson A, Blackburn DJ, Vijverberg EGB, De Deyn PP, Ducharme S, Jonsson M, Schneider A, Rinne JO, Ludolph AC, Bodenschatz R, Kordasiewicz H, Swayze EE, Fitzsimmons B, Mignon L, Moore KM, Yun C, Baumann T, Li D, Norris DA, Crean R, Graham DL, Huang E, Ratti E, Bennett CF, Junge C, Lane RM. Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial. Nat Med. 2023 Jun;29(6):1437-1447. doi: 10.1038/s41591-023-02326-3. Epub 2023 Apr 24.
PubMed 37095250