Alzheimer DiseasePhase 1NCT03522129
Study to Evaluate the Effect of CT1812 Treatment on Amyloid Beta Oligomer Displacement Into CSF in Subjects With Mild to Moderate Alzheimer's Disease
A Phase 1 study testing CT1812 in people with Alzheimer Disease, run by Cognition Therapeutics at 2 sites in United States.
Trial summary
This is a multi-center, Phase 1b, randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to moderate AD. Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- CT1812
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 May 2018to 6 Feb 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects may be included in the study only if they meet all of the following criteria:
- Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a diagnosis of mild to moderate Probable Alzheimer's Disease Dementia according to the 2011 NIA-AA criteria and at least a 6 month decline in cognitive function documented in the medical record.
- a. Non-childbearing potential for women is defined as postmenopausal [last natural menses greater than 24 months; in women under age 55, menopausal status will be documented with serum follicle stimulating hormone (FSH) test] or undergone a documented bilateral tubal ligation or hysterectomy
- b. Male participants who are sexually active with a woman of childbearing potential must agree to use condoms during the trial unless the woman is using an acceptable means of birth control. Acceptable forms of birth control include abstinence, birth control pills, or any double combination of: intrauterine device (IUD), male or female condom, diaphragm, sponge, and cervical cap.
- Neuromaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease and without findings of significant exclusionary abnormalities (see exclusion criteria, number 3).
- MMSE 18-26 inclusive. Subjects must, in the opinion of the investigator, be able to comply with study procedures and must understand the consent process. The investigator will use his or her clinical judgment in conjunction with the cognitive screening assessments to determine whether the subject meets these criteria in a manner that is consistent with local clinical practice and standards. Subjects with borderline low MMSE at screening may undergo repeat MMSE administration if extenuating circumstances were present at original assessment.
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- A positive amyloid scan (florbetaben F18, florbetapir F18, or flutametamol F18) at screening or within prior 12 months, as read by the certified, site-designated PET scan reader.
- Must consent to apolipoprotein E (ApoE) genotyping.
- Subjects must have a caregiver or study partner who can participate in all clinic visits.
- Patients living at home or in the community (assisted living acceptable).
- Able to swallow CT1812 capsules.
- Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening.
- Subjects must be capable of providing either written informed consent to the study procedures and for use of protected health information [Health Insurance Portability and Accountability Act (HIPAA) Authorization, if applicable]. Written informed consent also shall be obtained from the responsible caregiver or study partner. All consent processes must be undertaken in the presence of a witness and prior to any study procedures.
- Subjects shall be generally healthy with mobility (ambulatory or ambulatory-aided, i.e., walker or cane), vision and hearing (hearing aid permissible) sufficient for compliance with testing procedures.
- Must be able to complete all screening evaluations.
Who cannot join
- Subjects will be excluded from the study if any of the following conditions apply:
- Hospitalization or change of chronic concomitant medication within one month prior to screening.
- Patients living in a continuous care nursing facility
- Screening MRI of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct > 1 cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or brain tumor such as meningioma). If a small incidental meningioma is observed, the medical monitor may be contacted to discuss eligibility.
- Clinical or laboratory findings consistent with:
- Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Jacob-Creutzfeld Disease, Down syndrome, etc.);
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- Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.);
- Seizure disorder; or
- Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism.) Present vitamin B12 or folate deficiency or other laboratory abnormalities of possible clinical significance should be discussed with medical monitor to determine eligibility.
- A current DSM-V diagnosis that would interfere with the subject's ability to participate in the study. Patients with depressive symptoms successfully managed by a stable dose of an antidepressant are allowed entry.
- Any prior history of suicidal thoughts or behavior that are believed by the investigator to represent a current safety risk.
- Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as:
- Chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, > 1.5 ULN);
- Respiratory insufficiency;
- Renal insufficiency, defined as eGFR <40 mL/min based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula, https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr Heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within six months before screening). If a subject has a history of heart disease of questionable clinical significance, the medical monitor may be contacted to discuss eligibility.
- Bradycardia (<50 beats/min.) or tachycardia (>100 beats/min.). Otherwise healthy subjects with borderline bradycardia may be discussed with the medical monitor to determine eligibility.
- Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg) or hypotension (systolic <90 mm Hg and/or diastolic <60 mm Hg); or
- Uncontrolled diabetes defined by HbA1c >7.5
- History of cancer within 3 years of screening with the exception of fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at least 6 months.
- History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for Hepatitis B surface antigen [HbsAg] or anti-Hepatitis C [HCV] antibody).
- Clinically significant abnormalities in screening laboratory tests, including:
- hematocrit less than 35% for males and less than 32% for females
- platelet cell count of < 120,000/uL,
- INR >1.4 or other coagulopathy, confirmed by repeat analysis, or
- lymphocyte count less than 1200/ul
- Disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.).
- Within 4 weeks of screening visit or during the course of the study, concurrent treatment with antipsychotic agents, antiepileptics, centrally active anti-hypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine, etc.), sedatives, opioids, mood stabilizers (e.g., valproate, lithium); or benzodiazepines, with the following exceptions:
- benzodiazepines must not be administered within 5 half-lives of cognitive testing;
- administration of selective serotonin re-uptake inhibitors (SSRI) may be continued if doses have been stable for 60 days prior to Screening;
- low dose lorazepam may be used for sedation prior to MRI scan for those patients requiring sedation. At the discretion of the investigator, 0.5 to 1 mg may be given orally prior to scan with a single repeat dose given if the first dose is ineffective. No more than a total of 2 mg lorazepam may be used for the MRI scan.
- Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease, or liver disease.)
- Nootropic drugs except for AD meds (acetylcholinesterase inhibitors and memantine) stable for at least 30 days
- Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV significantly above normal value at screening.
- Suspected or known allergy to any components of the study treatments.
- Enrollment in another investigational study or intake of investigational drug within the previous 30 days or five half lives of the investigational drug, whichever is longer.
- Intake of drugs or substances potentially involved in clinically significant inhibition or induction of CYP3A4 or P-gp mediated drug interactions with CT1812, within 4 weeks or five half-lives of the interacting drug prior to administration of CT1812 and throughout the course of the study. Grapefruit juice should be avoided in the two weeks prior to dosing. See Appendix A and Appendix B for a complete list of prohibited substances.
- Previous exposure to anti Aβ vaccines.
- Exposure to passive immunotherapies for AD (e.g. monoclonal antibodies) within the previous 180 days to dosing, or BACE inhibitors within the previous 30 days to dosing..
- Contraindication to undergoing an LP including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; international normalized ratio (INR) > 1.4 or other coagulopathy; platelet count of <120,000/μL; infection at the desired lumbar puncture site; taking anti-coagulant medication within 90 days of screening (Note: low dose aspirin is permitted); degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma.
- Positive assay for Lyme disease if a screening lumbar puncture is conducted and includes this measurement.
- Any condition, which in the opinion of the investigator or the sponsor makes the patient unsuitable for inclusion.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Clinilabs Drug Development Corporation
New York, New York, 07724
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Pilot Study to Evaluate the Effect of CT1812 Treatment on Amyloid Beta Oligomer Displacement Into CSF in Subjects With Mild to Moderate Alzheimer's Disease
This is a multi-center, Phase 1b, randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to moderate AD.
Read the detailed description
This is a multi-center, Phase 1b, randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to moderate AD. The primary endpoint is the change from the baseline CSF Amyloid beta oligomer concentration after dosing with CT1812 versus placebo. The change from baseline will be measured through a number of exploratory endpoints as indicated below. For each subject, the baseline CSF oligomer concentration will be computed as the average of the measurements from hours -4, -3, -2 and -1 and 0.
- Conditions
- Alzheimer Disease
- Being tested
- CT1812, Placebo
- Keywords
- Alzheimer's Disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CT1812Drug
Also called Study Drug
Active Study Drug
PlaceboDrug
Also called Matching Placebo
Non-active study drug
| Study group | Role | What they receive |
|---|---|---|
| Active Treatment- CT1812 560 mg | Active comparator | Not described Receives: Drug: CT1812 |
| Active Treatment- CT1812 280 mg | Active comparator | Not described Receives: Drug: CT1812 |
| Active Treatment- CT1812 90 mg | Active comparator | Not described Receives: Drug: CT1812 |
| Placebo Comparator - Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measuring the displacement of Amyloid beta oligomers into cerebrospinal fluid (CSF)
evidence of oligomer displacement as demonstrated by a clear rise in CSF oligomer concentration relative to baseline and placebo
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2018
- Study start30 May 2018
- Primary completion6 Feb 2019
- Study completion6 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- 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
- Model description
- Phase 1b, randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to moderate AD.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cognition Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alyssa Galley, Study director, Cognition Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03522129
- Sponsor's protocol ID
- COG0104
- Status last verified
- Jan 2022
- First submitted
- 30 Apr 2018
- Last updated
- 12 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
LaBarbera KM, Sheline YI, Izzo NJ, Yuede CM, Waybright L, Yurko R, Edwards HM, Gardiner WD, Blennow K, Zetterberg H, Borjesson-Hanson A, Morgan R, Davis CS, Guttendorf RJ, Schneider LS, DeKosky S, LeVine H 3rd, Grundman M, Caggiano AO, Cirrito JR, Catalano SM, Hamby ME. A phase 1b randomized clinical trial of CT1812 to measure Abeta oligomer displacement in Alzheimer's disease using an indwelling CSF catheter. Transl Neurodegener. 2023 May 12;12(1):24. doi: 10.1186/s40035-023-00358-w. No abstract available.
PubMed 37173791
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Evaluate the Effect of CT1812 Treatment on Amyloid Beta Oligomer Displacement Into CSF in Subjects With Mild to Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03522129
- Acronym / sponsor ID
- COG0104
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Cognition TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 30 May 2018 (actual)
- Primary completion
- 6 Feb 2019 (actual)
- Study completion
- 6 Feb 2019 (actual)
- First posted
- 11 May 2018 (actual)
- 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 is a multi-center, Phase 1b, randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to moderate AD.
Detailed description
This is a multi-center, Phase 1b, randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to moderate AD. The primary endpoint is the change from the baseline CSF Amyloid beta oligomer concentration after dosing with CT1812 versus placebo. The change from baseline will be measured through a number of exploratory endpoints as indicated below. For each subject, the baseline CSF oligomer concentration will be computed as the average of the measurements from hours -4, -3, -2 and -1 and 0.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Phase 1b, randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to moderate AD.
| Arm | Type | Receives |
|---|---|---|
| Active Treatment- CT1812 560 mg | Active comparator | Drug: CT1812 |
| Active Treatment- CT1812 280 mg | Active comparator | Drug: CT1812 |
| Active Treatment- CT1812 90 mg | Active comparator | Drug: CT1812 |
| Placebo Comparator - Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a diagnosis of mild to moderate Probable Alzheimer's Disease Dementia according to the 2011 NIA-AA criteria and at least a 6 month decline in cognitive function documented in the medical record.
- Neuromaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease and without findings of significant exclusionary abnormalities (see exclusion criteria, number 3).
- MMSE 18-26 inclusive. Subjects must, in the opinion of the investigator, be able to comply with study procedures and must understand the consent process. The investigator will use his or her clinical judgment in conjunction with the cognitive screening assessments to determine whether the subject meets these criteria in a manner that is consistent with local clinical practice and standards. Subjects with borderline low MMSE at screening may undergo repeat MMSE administration if extenuating circumstances were present at original assessment.
- A positive amyloid scan (florbetaben F18, florbetapir F18, or flutametamol F18) at screening or within prior 12 months, as read by the certified, site-designated PET scan reader.
- Must consent to apolipoprotein E (ApoE) genotyping.
Key exclusion criteria (41 listed)
- Hospitalization or change of chronic concomitant medication within one month prior to screening.
- Patients living in a continuous care nursing facility
- Screening MRI of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct > 1 cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or brain tumor such as meningioma). If a small incidental meningioma is observed, the medical monitor may be contacted to discuss eligibility.
- Clinical or laboratory findings consistent with:
- A current DSM-V diagnosis that would interfere with the subject's ability to participate in the study. Patients with depressive symptoms successfully managed by a stable dose of an antidepressant are allowed entry.
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 |
|---|---|---|
| CT1812Also: Study DrugActive Study Drug | Drug | Active Treatment- CT1812 280 mg, Active Treatment- CT1812 560 mg, Active Treatment- CT1812 90 mg |
| PlaceboAlso: Matching PlaceboNon-active study drug | Drug | Placebo Comparator - Placebo |
Primary outcome
Measuring the displacement of Amyloid beta oligomers into cerebrospinal fluid (CSF)
Time frame: 48 hours
evidence of oligomer displacement as demonstrated by a clear rise in CSF oligomer concentration relative to baseline and placebo
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 12 Jan 2022.
- Derived from this study: PubMed 37173791LaBarbera KM, Sheline YI, Izzo NJ, Yuede CM, Waybright L, Yurko R, Edwards HM, Gardiner WD, Blennow K, Zetterberg H, Borjesson-Hanson A, Morgan R, Davis CS, Guttendorf RJ, Schneider LS, DeKosky S, LeVine H 3rd, Grundman M, Caggiano AO, Cirrito JR, Catalano SM, Hamby ME. A phase 1b randomized clinical trial of CT1812 to measure Abeta oligomer displacement in Alzheimer's disease using an indwelling CSF catheter. Transl Neurodegener. 2023 May 12;12(1):24. doi: 10.1186/s40035-023-00358-w. No abstract available.
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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.
Alyssa Galley study director
Cognition Therapeutics, Inc.
2 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 CT1812 in people with Alzheimer Disease, run by Cognition Therapeutics at 2 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 15 inclusion and 41 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 12 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Measuring the displacement of Amyloid beta oligomers into cerebrospinal fluid (CSF) (time frame: 48 hours). 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 NCT03522129, which also lists 1 linked publication.
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 12 Jan 2022.