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Alzheimer's DiseasePhase 2NCT03828747

A Study of Semorinemab in Patients With Moderate Alzheimer's Disease

A Phase 2 study testing Semorinemab and [18F]GTP1 in people with Alzheimer's Disease, run by Genentech, Inc. at 49 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in patients with moderate AD. Read more about this study

Who is it for?
Ages 50 to 85 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
Semorinemab and [18F]GTP1
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
272 participants
Where
49 sitesin 4 countries
Study dates
25 Jan 2019to 30 Aug 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • National Institute on Aging/Alzheimer's Association core clinical criteria for probable AD dementia
  • Evidence of the AD pathological process, by a positive amyloid assessment either on CSF Aβ1-42 as measured on Elecsys β-Amyloid(1-42) Test System OR amyloid PET scan
  • AD dementia of moderate severity, as defined by a screening MMSE score of 16-21 points, inclusive, and a CDR-GS of 1 or 2
  • Availability of a person with sufficient contact with the participant to be able to provide accurate information on the participant's cognitive, behavioral and functional ability

Who cannot join

  • Pregnant or breastfeeding
  • Inability to tolerate MRI procedures or contraindication to MRI
  • Contraindication to PET imaging
  • Residence in a skilled nursing facility
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or bias the assessment of the clinical or mental status of the participant to a significant degree
  • Any evidence of a condition other than AD that may affect cognition
Show all 14Show fewer
  • Substance abuse within the past 2 years
  • Use of any experimental therapy within 90 days or 5 half-lives prior to screening, whichever is greater, or any passive immunotherapy against tau
  • Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was at least 1 year prior to screening or any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline
  • Any other biologic therapy or previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other non-AD neurodegenerative disorder within 1 year of screening
  • Systemic immunosuppressive therapy within 12 months of screening through the entire study period
  • Typical antipsychotic or neuroleptic medication within 6 months of screening
  • Daily treatment with any of the following classes of medication (except for intermittent short-term use): opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally-acting antihistamine or anticholinergic activity
  • Stimulant medications, unless the dose has been stable within the 6 months prior to screening and is expected to be stable throughout the study

Trial locations and contacts

49 sites in 4 countries.

49 sites in 4 countries

United States31 sites
  • Abington Neurological Associates

    Abington, Pennsylvania, 19001

  • JEM Research LLC

    Atlantis, Florida, 33462

  • The Memory Clinic

    Bennington, Vermont, 05201

  • Brigham and Womens Hospital; Center for Alzheimer Research & Treatment

    Boston, Massachusetts, 02115

  • Bradenton Research Center

    Bradenton, Florida, 34205

  • Rush University Medical Center - Chicago

    Chicago, Illinois, 60612

  • Neurology Clinic PC

    Cordova, Tennessee, 38018

  • Brain Matters Research, Inc.

    Delray Beach, Florida, 33445

  • Rhode Island Mood & Memory Research Institute

    East Providence, Rhode Island, 02914

  • Alexian Brothers Neuroscience Institute

    Elk Grove Village, Illinois, 60007

  • Neuropsychiatric Research; Center of Southwest Florida

    Fort Myers, Florida, 33912

  • Collaborative Neuroscience Network, Inc.

    Garden Grove, California, 92845

  • New Orleans Center for Clinical Research

    Knoxville, Tennessee, 37920

  • Empire Neurology PC; MS Center of Northeastern NY

    Latham, New York, 12110

  • Pharmacology Research Institute

    Los Alamitos, California, 90720

  • Miami Jewish Health Systems

    Miami, Florida, 33137

  • Collier Neurologic Specialists

    Naples, Florida, 34105

  • Molecular Neuroimaging; MRI/PET

    New Haven, Connecticut, 06510

  • Synexus Clinical Research US, Inc. - Orlando

    Orlando, Florida, 32806

  • Stanford University; Stanford Clinical Cancer Ctr

    Palo Alto, California, 94305

  • Summit Research Network Inc.

    Portland, Oregon, 97210

  • Butler Hospital; Movement Disorders Program

    Providence, Rhode Island, 02906

  • Alzheimers Disease Center

    Quincy, Massachusetts, 02169

  • University of Rochester; AD-CARE

    Rochester, New York, 14642

  • Center for Memory and Aging

    Saint Paul, Minnesota, 55130

  • Pacific Research Network - PRN

    San Diego, California, 92103

  • Southern Illinois University, School of Medicine

    Springfield, Illinois, 62702

  • KI Health Partners, LLC; New England Institute for Clinical Research

    Stamford, Connecticut, 06905

  • Advanced Memory Research Institute of NJ

    Toms River, New Jersey, 08755

  • Alzheimer?s Research and Treatment Center

    Wellington, Florida, 33414

  • Premiere Research Institute

    West Palm Beach, Florida, 33407

Other trials in United States

Poland7 sites
  • Podlaskie Centrum Psychogeriatrii

    Bia?ystok, 15-756

  • Novo-Med Zielinski i wspolnicy Sp. j.

    Katowice, 40-650

  • NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek

    Późna, 61-853

  • Osrodek Badan Klinicznych Euromedis

    Szczecin, 70-111

  • Centrum Medyczne NeuroProtect

    Warsaw, 01-684

  • Centrum Medyczne AMED

    Warsaw, 03-291

  • NZOZ WCA

    Wroc?aw, 53-659

Other trials in Poland

Spain6 sites
  • Fundacio ACE

    Barcelona, 08028

  • Hospital Clinic I Provincial

    Barcelona, 08036

  • Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia

    Barcelona, 08041

  • Hospital Mutua de Terrassa

    Terrassa, Barcelona, 08221

  • Hospital Universitario Doctor Peset

    Valencia, 46017

  • Hospital Universitari i Politecnic La Fe

    Valencia, 46026

Other trials in Spain

France5 sites
  • Chu Toulouse

    Bron, 69500

  • CHU de la Timone - Hopital d Adultes; Service de Neurologie

    Marseille, 13005

  • Groupe Hospitalier Pitie-Salpetriere

    Paris, 75651

  • CHU Rennes - Hopital Pontchaillou

    Rennes, 35033

  • Hopital des Charpennes

    Villeurbanne, 69100

Other trials in France

About this study

Official title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Moderate Alzheimer's Disease

This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in patients with moderate AD. The study consists of a screening period, a double-blind treatment period, an optional open-label extension (OLE) period, and a safety follow-up period. There may be up to two study cohorts.

Being tested
Semorinemab, Placebo, [18F]GTP1
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SemorinemabDrug

    Also called MTAU9937A, RO7105705

    Participants will receive semorinemab every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. Semorinemab will be administered Q4W in the OLE period.

  • PlaceboDrug

    Participants will receive placebo every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period.

  • [18F]GTP1Drug

    [18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.

Study groups in NCT03828747
Study groupRoleWhat they receive
SemorinemabExperimentalSemorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.
Receives: Drug: Semorinemab; Drug: [18F]GTP1
PlaceboPlacebo comparatorPlacebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Receives: Drug: Placebo; Drug: [18F]GTP1

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

    The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.

    Measured: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

  2. Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

    The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.

    Measured: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

Secondary outcomes (12)
  1. Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

    The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.

    Measured: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

  2. Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

    The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.

    Measured: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

  3. Percentage of Participants With Adverse Events

    An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

    Measured: Baseline up to end of study (approximately 4 years and 7 months)

  4. Serum Concentration of RO7105705 at Specified Timepoints

    Measured: Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

  5. Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

    Measured: Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

  6. Relationship Between ADA Status and Percentage of Participants With Adverse Events

    Descriptive statistics will be used for assessment.

    Measured: Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.

  7. Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

    Descriptive statistics will be used for assessment.

    A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function.

    Measured: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

  8. Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

    Descriptive statistics will be used for assessment.

    A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.

    Measured: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

  9. Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

    Descriptive statistics will be used for assessment.

    A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.

    Measured: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

  10. Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

    Descriptive statistics will be used for assessment.

    The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.

    Measured: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

  11. Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints

    Descriptive statistics will be used for assessment.

    Measured: Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

  12. Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

    Descriptive statistics will be used for assessment.

    Measured: Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2019
  2. Study start25 Jan 2019
  3. Primary completion20 Jul 2021
  4. Study completion30 Aug 2023

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
272 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03828747
Sponsor's protocol ID
GN40040
Status last verified
Aug 2024
First submitted
29 Jan 2019
Last updated
24 Sep 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm)

Publications

  • Chandler JM, Lansdall CJ, Ye W, McDougall F, Belger M, Toth B, Mi X, Sink KM, Atkins AS. The Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity. J Prev Alzheimers Dis. 2025 Sep;12(8):100261. doi: 10.1016/j.tjpad.2025.100261. Epub 2025 Jul 1.

    PubMed 40603145
  • Schauer SP, Toth B, Lee J, Honigberg LA, Ramakrishnan V, Jiang J, Kollmorgen G, Bayfield A, Wild N, Hoffman J, Ceniceros R, Dolton M, Bohorquez SMS, Hoogenraad CC, Wildsmith KR, Teng E, Monteiro C, Anania V, Yeh FL. Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer's disease pathophysiology. Alzheimers Dement. 2024 Dec;20(12):8855-8866. doi: 10.1002/alz.14346. Epub 2024 Nov 8.

    PubMed 39513754
  • Ramakrishnan V, Bender B, Langenhorst J, Magnusson MO, Dolton M, Shim J, Fuji RN, Monteiro C, Teng E, Kassir N, Jin J. Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies. J Prev Alzheimers Dis. 2024;11(5):1241-1250. doi: 10.14283/jpad.2024.146.

    PubMed 39350369
  • Monteiro C, Toth B, Brunstein F, Bobbala A, Datta S, Ceniceros R, Sanabria Bohorquez SM, Anania VG, Wildsmith KR, Schauer SP, Lee J, Dolton MJ, Ramakrishnan V, Abramzon D, Teng E; Lauriet investigators. Randomized Phase II Study of the Safety and Efficacy of Semorinemab in Participants With Mild-to-Moderate Alzheimer Disease: Lauriet. Neurology. 2023 Oct 3;101(14):e1391-e1401. doi: 10.1212/WNL.0000000000207663. Epub 2023 Aug 29.

    PubMed 37643887

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Semorinemab and [18F]GTP1 in people with Alzheimer's Disease, run by Genentech, Inc. at 49 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, Poland, Spain, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) (time frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03828747, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2024.

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