Alzheimer DiseasePhase 1NCT02353598
A Study of Crenezumab in Participants With Mild to Moderate Alzheimer Disease
A Phase 1 study testing Crenezumab dose level 1, Crenezumab dose level 2 and Crenezumb dose level 3 in people with Alzheimer Disease, run by Genentech, Inc. at 13 sites in United States.
Trial summary
This randomized, placebo-controlled, double-blind, parallel-arm study will evaluate the safety and tolerability of at least two dose levels of intravenous (IV) crenezumab in 24-72 participants with mild to moderate Alzheimer disease (AD) (mini-mental state examination [MMSE] 18 to 28 points, inclusive). Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Crenezumab dose level 1, Crenezumab dose level 2 and Crenezumb dose level 3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 77 participants
- Where
- 13 sitesUnited States
- Study dates
- 26 Feb 2015to 26 Mar 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Body weight greater than or equal (>/=) 45 kilograms (kg) and less than or equal (</=) 120 kg
- Ages 50-90 years, inclusive
- Availability of a person ("caregiver") who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits, which require partner input for scale completion, and signs the necessary consent form
- Willingness and ability to complete all aspects of the study; the participant should be capable of completing assessments either alone or with the help of the caregiver
- Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing
- Clinical diagnosis of probable mild to moderate AD based on the national institute on neurological and communication disease and stroke/Alzheimer's disease and related disorders association (NINCDS/ADRDA) criteria or probable major neurocognitive disorder due to AD of mild to moderate severity based on diagnostic and statistical manual of mental disorders, version 5 (DSM-5) criteria
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- Screening MMSE score of 18-28 points, inclusive
- Screening clinical dementia rating global score (CDR-GS) of 0.5 or 1.0
- Screening geriatric depression (GDS)-15 score less than (<) 6
- Positive florbetapir amyloid positron emission tomography (PET) scan by qualitative read conducted by the core/central PET laboratory
- Women must be postmenopausal or surgically sterile
- Men with female partners of childbearing potential agree to remain abstinent or use adequate methods of contraception as defined by protocol during the treatment period and for at least 8 weeks after the last dose of study drug and agreement to refrain from donating sperm during this same period
Who cannot join
- History or presence of clinically evident vascular disease potentially affecting the brain that, in the opinion of the investigator, has the potential to affect cognitive function
- History or presence of stroke within the previous 2 years or documented history of transient ischemic attack within the previous 12 months
- History of severe, clinically significant central nervous system trauma
- History or presence of intracranial tumor that is clinically relevant in the opinion of the investigator
- Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
- History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits
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- History or presence of a neurologic disease other than AD that may affect cognition
- Presence of superficial siderosis, more than four cerebral microhemorrhages, or evidence of a prior cerebral macrohemorrhage
- Inability to tolerate magnetic resonance imaging (MRI) procedures or contraindication to MRI
- History or presence of atrial fibrillation except if only one episode that resolved more than 1 year ago and for which treatment is no longer indicated or that in the investigator's judgment poses no risk for future stroke
- Within the previous 2 years, unstable or clinically significant cardiovascular disease
- Uncontrolled hypertension
- Chronic kidney disease of Stage >/= 4, according to the national kidney foundation kidney disease outcomes quality initiative (NKF KDOQI) guidelines for chronic kidney disease
- Impaired hepatic function
- Clinically significantly abnormal screening blood or urine that remain abnormal on retest
- History of malignancies within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer; cancer that is considered likely to be cured, is not being actively treated with anti-cancer therapy or radiotherapy and not likely to require treatment in the ensuing 5 years as well as cancers that are considered to have low probability of recurrence are allowed
- Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
- Severe or unstable medical condition that, in the opinion of the investigator or sponsor, could be expected to progress, recur, or change to such an extent that it could put the patient at special risk, bias the assessment of the clinical or mental status of the patient to a significant degree, interfere with the patient's ability to complete the study assessments, or would require the equivalent of institutional or hospital care
- Any previous treatment with medications used to treat Parkinsonian symptoms or any other neurodegenerative disorder within 1 year before screening even if the patient is taking the medicine for a non-neurodegenerative disorder such as restless leg disorder
- Typical anti-psychotic or neuroleptic medication within 6 months before screening except as brief treatment for a non-psychiatric indication
- Antihemostasis medication within 2 weeks before screening
- Sedative, hypnotic, or benzodiazepine medication within 3 months before screening except intermittent use of the following for sleep or anxiety: alprazolam, lorazepam, oxazepam, temazepam, diazepam, or a short-acting benzodiazepine-like medication
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Roper St. Francis Healthcare; Clinical Biotechnology Research Institute
Charleston, South Carolina, 29401
Brain Matters Research, Inc.
Delray Beach, Florida, 33445
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, 02914
Hattiesburg Clinic
Hattiesburg, Mississippi, 39401
Indiana University School Of Medicine; Department Of Neurology
Indianapolis, Indiana, 46202
Miami Jewish Health Systems
Miami, Florida, 33137
Columbia University Medical Center
New York, New York, 10032
Bioclinica Orlando
Orlando, Florida, 32806
Mayo Clinic Scottsdale
Phoenix, Arizona, 85054
UNiversity of Rochester
Rochester, New York, 14620
UCSF - Memory and Aging Center
San Francisco, California, 94158
Millennium Psychiatric Associates, LLC
St Louis, Missouri, 63132
Bioclinica The Villages
The Villages, Florida, 32162
About this study
Official title: A Phase Ib, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel-Arm, Multiple-Dose Study to Assess The Safety, Tolerability, And Pharmacokinetics of Intravenous Crenezumab Administered in Patients With Mild to Moderate Alzheimer's Disease
This randomized, placebo-controlled, double-blind, parallel-arm study will evaluate the safety and tolerability of at least two dose levels of intravenous (IV) crenezumab in 24-72 participants with mild to moderate Alzheimer disease (AD) (mini-mental state examination [MMSE] 18 to 28 points, inclusive). An optional open-label extension (OLE) will be offered after the completion of initial double-blind stage.
- Conditions
- Alzheimer Disease
- Being tested
- Crenezumab dose level 1, Crenezumab dose level 2, Crenezumb dose level 3, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crenezumab dose level 1Drug
Participants will receive crenezumb dose level 1 IV infusion once every 4 weeks up to Week 13 in double-blind treatment window or up to Week 61 in optional OLE window.
Crenezumab dose level 2Drug
Participants will receive crenezumb dose level 2 IV infusion once every 4 weeks up to Week 13 in double-blind treatment window or up to Week 61 in optional OLE window.
Crenezumb dose level 3Drug
Participants will receive crenezumb dose level 3 IV infusion once every 4 weeks upto Week 13 in double-blind treatment window or up to Week 61 in optional OLE window.
PlaceboDrug
Participants will receive placebo matched to crenezumab IV infusion once every 4 weeks upto Week 13 in double-blind treatment window.
| Study group | Role | What they receive |
|---|---|---|
| Double-blind treatment window: Crenezumab dose level 1 | Experimental | Participants will recieve crenezumab dose level 1 once every 4 weeks. Receives: Drug: Crenezumab dose level 1 |
| Double-blind treatment window: Crenezumab dose level 2 | Experimental | Participants will receive crenezumab dose level 2 once every 4 weeks. Receives: Drug: Crenezumab dose level 2 |
| Double-blind treatment window: Crenezumab dose level 3 | Experimental | Participants will receive crenezumab dose level 3 once every 4 weeks. Receives: Drug: Crenezumb dose level 3 |
| Double-blind treatment window: Placebo | Placebo comparator | Participants will receive placebo matched to crenezumab once every 4 weeks. Receives: Drug: Placebo |
| Optional OLE window: Crenezumab | Experimental | Participants will receive crenezumab dose levels 1 2, or 3 once in every 4 weeks. Receives: Drug: Crenezumab dose level 1; Drug: Crenezumab dose level 2; Drug: Crenezumb dose level 3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with anti-crenezumab antibodies
Measured: From baseline up to follow-up period (Week 69)
Number of participants with suicidal ideation, suicidal behavior, and self-injurious behavior without suicidal intent, as determined using the columbia-cuicide severity rating scale (C-SSRS)
Measured: From baseline up to follow-up period (Week 69)
Number of participants with changes from baseline in vital signs, electrocardiogram (ECG) and clinical laboratory results
Measured: From baseline up to follow-up period (Week 69)
Number of participants with amyloid-related imaging abnormalities-hemorrhage (ARIA-H)
Measured: Up to Week 13
Number of participants with adverse events (AEs) and serious adverse events (SAEs) according to national cancer institute common terminology criteria for adverse events, version 4.0 (NCICTCAE v4.0)
Measured: From baseline up to follow-up period (Week 69)
Number of participants with of non-serious AEs of special interest
Measured: From baseline up to follow-up period (Week 69)
Number of participants with amyloid-related imaging abnormalities-edema/effusion (ARIA-E)
Measured: Up to Week 13
Secondary outcomes (1)
Serum concentration of crenezumab
Measured: Pre-dose on Day 1, 60-90 minutes (min) post infusion on Day 1, Days 2, 8, Week 2, pre-dose and 60-90 min post infusion on dosing day of Weeks 5, 9, 13, and 21; pre-dose and 60-90 min post infusion on dosing day of Weeks 25, 53, 61, and 69
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2015 (estimated)
- Study start26 Feb 2015
- Primary completion30 Nov 2016
- Study completion26 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Genentech, 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02353598
- Sponsor's protocol ID
- GN29632
- Status last verified
- Jul 2019
- First submitted
- 23 Jan 2015
- Last updated
- 24 Jul 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Guthrie H, Honig LS, Lin H, Sink KM, Blondeau K, Quartino A, Dolton M, Carrasco-Triguero M, Lian Q, Bittner T, Clayton D, Smith J, Ostrowitzki S. Safety, Tolerability, and Pharmacokinetics of Crenezumab in Patients with Mild-to-Moderate Alzheimer's Disease Treated with Escalating Doses for up to 133 Weeks. J Alzheimers Dis. 2020;76(3):967-979. doi: 10.3233/JAD-200134.
PubMed 32568196Yoshida K, Moein A, Bittner T, Ostrowitzki S, Lin H, Honigberg L, Jin JY, Quartino A. Pharmacokinetics and pharmacodynamic effect of crenezumab on plasma and cerebrospinal fluid beta-amyloid in patients with mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2020 Jan 22;12(1):16. doi: 10.1186/s13195-020-0580-2.
PubMed 31969177
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel-Arm, Multiple-Dose Study to Assess The Safety, Tolerability, And Pharmacokinetics of Intravenous Crenezumab Administered in Patients With Mild to Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT02353598
- Acronym / sponsor ID
- GN29632
- Conditions
- Alzheimer Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 26 Feb 2015 (actual)
- Primary completion
- 30 Nov 2016 (actual)
- Study completion
- 26 Mar 2019 (actual)
- First posted
- 3 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized, placebo-controlled, double-blind, parallel-arm study will evaluate the safety and tolerability of at least two dose levels of intravenous (IV) crenezumab in 24-72 participants with mild to moderate Alzheimer disease (AD) (mini-mental state examination [MMSE] 18 to 28 points, inclusive). An optional open-label extension (OLE) will be offered after the completion of initial double-blind stage.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Double-blind treatment window: Crenezumab dose level 1 | Experimental | Drug: Crenezumab dose level 1Participants will recieve crenezumab dose level 1 once every 4 weeks. |
| Double-blind treatment window: Crenezumab dose level 2 | Experimental | Drug: Crenezumab dose level 2Participants will receive crenezumab dose level 2 once every 4 weeks. |
| Double-blind treatment window: Crenezumab dose level 3 | Experimental | Drug: Crenezumb dose level 3Participants will receive crenezumab dose level 3 once every 4 weeks. |
| Double-blind treatment window: Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo matched to crenezumab once every 4 weeks. |
| Optional OLE window: Crenezumab | Experimental | Drug: Crenezumab dose level 1, Drug: Crenezumab dose level 2, Drug: Crenezumb dose level 3Participants will receive crenezumab dose levels 1 2, or 3 once in every 4 weeks. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Body weight greater than or equal (>/=) 45 kilograms (kg) and less than or equal (</=) 120 kg
- Ages 50-90 years, inclusive
- Availability of a person ("caregiver") who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits, which require partner input for scale completion, and signs the necessary consent form
- Willingness and ability to complete all aspects of the study; the participant should be capable of completing assessments either alone or with the help of the caregiver
- Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing
Key exclusion criteria (22 listed)
- History or presence of clinically evident vascular disease potentially affecting the brain that, in the opinion of the investigator, has the potential to affect cognitive function
- History or presence of stroke within the previous 2 years or documented history of transient ischemic attack within the previous 12 months
- History of severe, clinically significant central nervous system trauma
- History or presence of intracranial tumor that is clinically relevant in the opinion of the investigator
- Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
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 |
|---|---|---|
| Crenezumab dose level 1Participants will receive crenezumb dose level 1 IV infusion once every 4 weeks up to Week 13 in double-blind treatment window or up to Week 61 in optional OLE window. | Drug | Double-blind treatment window: Crenezumab dose level 1, Optional OLE window: Crenezumab |
| Crenezumab dose level 2Participants will receive crenezumb dose level 2 IV infusion once every 4 weeks up to Week 13 in double-blind treatment window or up to Week 61 in optional OLE window. | Drug | Double-blind treatment window: Crenezumab dose level 2, Optional OLE window: Crenezumab |
| Crenezumb dose level 3Participants will receive crenezumb dose level 3 IV infusion once every 4 weeks upto Week 13 in double-blind treatment window or up to Week 61 in optional OLE window. | Drug | Double-blind treatment window: Crenezumab dose level 3, Optional OLE window: Crenezumab |
| PlaceboParticipants will receive placebo matched to crenezumab IV infusion once every 4 weeks upto Week 13 in double-blind treatment window. | Drug | Double-blind treatment window: Placebo |
Primary outcome
Number of participants with anti-crenezumab antibodies
Time frame: From baseline up to follow-up period (Week 69)
Number of participants with suicidal ideation, suicidal behavior, and self-injurious behavior without suicidal intent, as determined using the columbia-cuicide severity rating scale (C-SSRS)
Time frame: From baseline up to follow-up period (Week 69)
Number of participants with changes from baseline in vital signs, electrocardiogram (ECG) and clinical laboratory results
Time frame: From baseline up to follow-up period (Week 69)
Number of participants with amyloid-related imaging abnormalities-hemorrhage (ARIA-H)
Time frame: Up to Week 13
Number of participants with adverse events (AEs) and serious adverse events (SAEs) according to national cancer institute common terminology criteria for adverse events, version 4.0 (NCICTCAE v4.0)
Time frame: From baseline up to follow-up period (Week 69)
Number of participants with of non-serious AEs of special interest
Time frame: From baseline up to follow-up period (Week 69)
Number of participants with amyloid-related imaging abnormalities-edema/effusion (ARIA-E)
Time frame: Up to Week 13
1 secondary outcome
Serum concentration of crenezumab
Time frame: Pre-dose on Day 1, 60-90 minutes (min) post infusion on Day 1, Days 2, 8, Week 2, pre-dose and 60-90 min post infusion on dosing day of Weeks 5, 9, 13, and 21; pre-dose and 60-90 min post infusion on dosing day of Weeks 25, 53, 61, and 69
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
- Derived from this study: PubMed 32568196Guthrie H, Honig LS, Lin H, Sink KM, Blondeau K, Quartino A, Dolton M, Carrasco-Triguero M, Lian Q, Bittner T, Clayton D, Smith J, Ostrowitzki S. Safety, Tolerability, and Pharmacokinetics of Crenezumab in Patients with Mild-to-Moderate Alzheimer's Disease Treated with Escalating Doses for up to 133 Weeks. J Alzheimers Dis. 2020;76(3):967-979. doi: 10.3233/JAD-200134.
- Derived from this study: PubMed 31969177Yoshida K, Moein A, Bittner T, Ostrowitzki S, Lin H, Honigberg L, Jin JY, Quartino A. Pharmacokinetics and pharmacodynamic effect of crenezumab on plasma and cerebrospinal fluid beta-amyloid in patients with mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2020 Jan 22;12(1):16. doi: 10.1186/s13195-020-0580-2.
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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
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Crenezumab dose level 1, Crenezumab dose level 2 and Crenezumb dose level 3 in people with Alzheimer Disease, run by Genentech, Inc. at 13 sites in United States.
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 12 inclusion and 22 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 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of participants with anti-crenezumab antibodies (time frame: From baseline up to follow-up period (Week 69)). The study lists 7 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 NCT02353598, which also lists 2 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 Jul 2019.