Alzheimer DiseasePhase 2NCT03977584

Tau Positron Emission Tomography (PET) Longitudinal Substudy Associated With: Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers in the Treatment of Autosomal-Dominant Alzheimer's Disease

A Phase 2 study testing Crenezumab and [^18F]GTP1 in people with Alzheimer Disease, run by Hoffmann-La Roche at 1 site in Colombia.

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

Who is it for?: Ages 30 to 60 years
Conditions the study is for: Alzheimer Disease
What is being tested?: Crenezumab and [^18F]GTP1
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 114 participants
Where: 1 siteColombia
Study dates: 10 Jun 2019to 19 Apr 2022
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 30 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Enrolled in main Study NCT01998841 (GN28352).

Who cannot join

Contraindication to PET scan procedures, possibly including, but not limited to current, past, or planned participation in studies involving radioactive agents, including the main Study NCT01998841 (GN28352) and this Tau PET substudy, such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.

Trial locations and contacts

1 site in 1 country.

Colombia1 site

Grupo Neurociencias de Antioquia
Medellín

Other trials in Colombia

About this study

Official title: Tau PET Longitudinal Substudy Associated With: A Double-Blind, Placebo-Controlled Parallel-Group Study in Preclinical PSEN1 E280A Mutation Carriers Randomized to Crenezumab or Placebo, and in Non-randomized, Placebo-treated Non-carriers From the Same Kindred, to Evaluate the Efficacy and Safety of Crenezumab in the Treatment of Autosomal-Dominant Alzheimer's Disease

This substudy will evaluate the effect of crenezumab on the longitudinal tau burden in a subgroup of preclinical Presenilin1 (PSEN1) E280A mutation carriers and non-carriers, who were enrolled in study NCT01998841 (GN28352). Participants will receive up to three intravenous (IV) injections of [^18F] Genentech Tau Probe 1 (GTP1) and will undergo a tau positron emission tomography (PET) scan after each IV injection of [18^F]GTP1. The purpose of this substudy is to increase the understanding of disease progression in the preclinical stage of familial Alzheimer's Disease (AD).

Conditions: Alzheimer Disease
Being tested: Crenezumab, 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.

CrenezumabDrug
Also called MABT5102A
Crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.
PlaceboDrug
Placebo matched to crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.
[^18F]GTP1Other
IV [^18F]GTP1 will be administered up to three times. The first primary [^18F]GTP1 tau PET scan will occur during any visit in the main protocol NCT01998841 (GN28352) from Week 130 to Week 224 and the second [^18F]GTP1 tau PET scan from Week 248 to Week 260. The third and optional [^18F]GTP1 tau PET scan will supplement the two primary scans.

Study groups in NCT03977584
Study group	Role	What they receive
[^18F]GTP1 in Mutation Carriers: Crenezumab	Experimental	Mutation-carrying participants receiving crenezumab in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1. Receives: Drug: Crenezumab; Other: [^18F]GTP1
[^18F]GTP1 in Mutation Carriers: Placebo	Placebo comparator	Mutation-carrying participants receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1. Receives: Drug: Placebo; Other: [^18F]GTP1
[^18F]GTP1 in Non-carriers of Mutation: Placebo	Placebo comparator	Non-carriers of the mutation receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1. Receives: Drug: Placebo; Other: [^18F]GTP1

What is being measured

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

Annualized Rate of Change in Tau Burden
Tau is a protein that accumulates in Alzheimer's disease and damages brain cells including those essential for learning and memory. The effect of crenezumab on tau burden was assessed using [18F]GTP1 Tau PET. The annualized rate of change in tau burden from the first [18F]GTP1 scan of the standardized uptake ratio (SUVR) in the entorhinal cortex (Braak Stage 1) with an inferior cerebellum reference region was analyzed using a random coefficient regression model (RCRM). Braak staging classifies the degree of pathology in Alzheimer's disease. Braak stages 1 and 2 are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain, stages 3 and 4 when there is also involvement of limbic regions such as the hippocampus, and 5 and 6 when there is extensive neocortical involvement.
Measured: Baseline up to Week 149

Timeline

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

10 Jun 201919 Apr 2022

First posted6 Jun 2019
Study start10 Jun 2019
Primary completion19 Apr 2022
Study completion19 Apr 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.
Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe 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 2
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 114 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03977584
Sponsor's protocol ID: BN40199
Status last verified: Mar 2024
First submitted: 5 Jun 2019
Last updated: 15 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
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.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). 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).

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Alzheimer Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Tau PET Longitudinal Substudy Associated With: A Double-Blind, Placebo-Controlled Parallel-Group Study in Preclinical PSEN1 E280A Mutation Carriers Randomized to Crenezumab or Placebo, and in Non-randomized, Placebo-treated Non-carriers From the Same Kindred, to Evaluate the Efficacy and Safety of Crenezumab in the Treatment of Autosomal-Dominant Alzheimer's Disease
ClinicalTrials.gov ID: NCT03977584
Acronym / sponsor ID: BN40199
Conditions: Alzheimer Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 114 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Collaborators: Banner Alzheimer's Institute, National Institute on Aging (NIA)
Study start: 10 Jun 2019 (actual)
Primary completion: 19 Apr 2022 (actual)
Study completion: 19 Apr 2022 (actual)
First posted: 6 Jun 2019 (actual)
Results: Posted 15 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
[^18F]GTP1 in Mutation Carriers: Crenezumab	Experimental	Drug: Crenezumab, Other: [^18F]GTP1Mutation-carrying participants receiving crenezumab in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.
[^18F]GTP1 in Mutation Carriers: Placebo	Placebo comparator	Drug: Placebo, Other: [^18F]GTP1Mutation-carrying participants receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.
[^18F]GTP1 in Non-carriers of Mutation: Placebo	Placebo comparator	Drug: Placebo, Other: [^18F]GTP1Non-carriers of the mutation receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.

Who may qualify

Ages: 30 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (1 listed)

Enrolled in main Study NCT01998841 (GN28352).

Key exclusion criteria (1 listed)

Contraindication to PET scan procedures, possibly including, but not limited to current, past, or planned participation in studies involving radioactive agents, including the main Study NCT01998841 (GN28352) and this Tau PET substudy, such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CrenezumabAlso: MABT5102ACrenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.	Drug	[^18F]GTP1 in Mutation Carriers: Crenezumab
PlaceboPlacebo matched to crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.	Drug	[^18F]GTP1 in Mutation Carriers: Placebo, [^18F]GTP1 in Non-carriers of Mutation: Placebo
[^18F]GTP1IV [^18F]GTP1 will be administered up to three times. The first primary [^18F]GTP1 tau PET scan will occur during any visit in the main protocol NCT01998841 (GN28352) from Week 130 to Week 224 and the second [^18F]GTP1 tau PET scan from Week 248 to Week 260. The third and optional [^18F]GTP1 tau PET scan will supplement the two primary scans.	Other	[^18F]GTP1 in Mutation Carriers: Crenezumab, [^18F]GTP1 in Mutation Carriers: Placebo, [^18F]GTP1 in Non-carriers of Mutation: Placebo

Primary outcome

Annualized Rate of Change in Tau Burden
Time frame: Baseline up to Week 149
Tau is a protein that accumulates in Alzheimer's disease and damages brain cells including those essential for learning and memory. The effect of crenezumab on tau burden was assessed using [18F]GTP1 Tau PET. The annualized rate of change in tau burden from the first [18F]GTP1 scan of the standardized uptake ratio (SUVR) in the entorhinal cortex (Braak Stage 1) with an inferior cerebellum reference region was analyzed using a random coefficient regression model (RCRM). Braak staging classifies the degree of pathology in Alzheimer's disease. Braak stages 1 and 2 are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain, stages 3 and 4 when there is also involvement of limbic regions such as the hippocampus, and 5 and 6 when there is extensive neocortical involvement.

Results and safety

Results posted to the registry on 15 Mar 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Crenezumab - Mutation Carriers	44	42
Placebo - Mutation Carriers	39	39
Placebo - Non-Carriers of Mutation	31	27

Primary outcome: Annualized Rate of Change in Tau Burden

Time frame: Baseline up to Week 149. Mean (Standard Error). Unit: SUVR per year

Measure	Crenezumab - Mutation Carriers n = 44	Placebo - Mutation Carriers n = 39
Value	0.0124 (0.00752)	0.0254 (0.00768)

Crenezumab - Mutation Carriers vs Placebo - Mutation Carriers: Difference in Annualized Rate of Change: -0.0130 (95% CI -0.0327 to 0.0068), p = 0.1953, RCRM

Population analysed: Modified Intent-to-Treat (mITT) population included all mutation carrier participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug.

Adverse events

Time frame: Up to Week 149. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Crenezumab - Mutation Carriers	4 of 44 (9.1%)	43 of 44 (97.7%)	0 of 44
Pooled Placebo	5 of 70 (7.1%)	67 of 70 (95.7%)	0 of 70
Combined Blinded	9 of 114 (7.9%)	110 of 114 (96.5%)	0 of 114

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). 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).

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Crenezumab and [^18F]GTP1 in people with Alzheimer Disease, run by Hoffmann-La Roche at 1 site in Colombia.

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 1 inclusion and 1 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 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Colombia. 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 15 Mar 2024). 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?

Annualized Rate of Change in Tau Burden (time frame: Baseline up to Week 149). 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 NCT03977584.

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 15 Mar 2024.