Early Alzheimer’s Disease MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimers disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: Trappsol® Cyclo™
Product Code: NA
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Hydroxypropylbetadex
CAS Number: 128446-35-5
Current Sponsor code: NA
Other descriptive
Sponsors
Cyclo Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female =50 to =80 years of age, at the time of consent. a. Able to review and understand the clinical trial info and to give self-competent informed consent b. Have at least an eighth-grade education. c. Primary language for Austria based patients must be German and patients should be able to understand and read German at a level that will ensure adequate completion of study procedures including informed consent and all cognitive tests. 2. MCI due to AD (Stage 3) according to the FDA Guidance for Industry on EAD: Developing Drugs for Treatment:68 a. Meet the NIA-AA criteria for MCI due to AD.12,30 b. Have a global Clinical Dementia Rating (CDR) scale score of 0.5 and a CDR Memory Box score of 0.5 or greater at both Screening and Baseline. c. History of memory complaint/decline reported by patient or partner/caregiver with gradual onset and slow progression over the last 1 year before Screening. d. In the opinion of the Investigator based on patient and caregiver review, relatively preserved functional abilities and activities of daily living. OR Mild AD dementia (Stage 4) a. Meet the NIA-AA criteria for mild AD dementia. b. Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of 0.5 or greater at both Screening and Baseline. 3. All patients should have an MMSE2:SV score =20 and =28 at both Screening and Baseline with no more than a 3 point change between visits. 4. CSF biomarker for supporting the diagnosis of AD. The test result to determine cerebral Aß pathology must be known prior to enrollment at Baseline. 5. MRI of the brain performed during the screening period or within the prior 12 months that is not contradictory of AD diagnosis upon local read. 6. Locally or centrally read MRI of ARIA suggesting less than 4 microhemorrhages. 7. Have a primary caregiver who has sufficient contact with the patient, is able to provide assessment of cognitive and functional changes and is willing to accept primary responsibility for supervising the patient and assessing the condition of the patient throughout the study in accordance with protocol requirements. The primary caregiver must meet the following criteria: a. Be able and willing to provide information needed for efficacy assessments such as CDR-SB. b. Willing to sign the caregiver informed consent. 8. Not likely to experience a change in living conditions or change in primary caregiver during participation in the trial. 9. Standard of care therapy for AD with acetylcholine esterase inhibitors and/or memantine are allowed as long as the dose has been stable for at least 60 days prior to Screening and is expected to remain stable for the study duration. NOTE: Treatment-naïve patients desiring starting on standard of care, can start such treatment. In this case they can be re-screened after 60 days of stable treatment. 10. Background medications used for other stable chronic illnesses that are not expressly prohibited are also allowed provided that they remain stable for the study duration: a. Psychotropics, such as antidepressants and antipsychotics, must be at a stable dose for at least 30 days prior to Screening and remain stable throughout the study duration within the framework and regimen in Section 6.7. b. Short-acting benzodiazepines for sleep can be used up to 3/week but not within 24 hours of cognitive assessments. 11. All patients must pass a brief audiologic examination including pure tone audiometry (see also exclusion criteria 17). 12. Body mas
Exclusion criteria
Exclusion criteria: 1. Not able to give informed consent based on their cognitive abilities 2. Clinically significant renal disease that in the opinion of the Investigator precludes the patient from participating in the study. 3. Evidence of a neurodegenerative disease other than AD or any medical history or brain imaging abnormality that might cause the dementia in the opinion of the Investigator. 4. Severe hypothyroidism that is refractory to standard of care and with no or inadequate response to clinically relevant dosage of levothyroxine as determined by thyroid-stimulating hormone, T3 and T4, and presentation of clinical signs and symptoms. 5. Abnormally low levels of serum Vitamin B12. 6. Imaging should be generally supportive of the diagnosis of EAD and, importantly, not consistent with other neurodegenerative disorder or differential dementia diagnoses. For example, any suggestion of vascular disease, including multiple infarction involving large blood vessels or localized single infarction, multiple lacunae of the basal nuclei or white matter or extensive lesions of the periventricular white matter or combination of several lesions are considered exclusionary. Additionally, any single lacuna in an area known to impact cognition such as the hippocampus will also be exclusionary. a. In cases of prior MRI scans used for inclusion, should there be any evidence of new neurological symptoms between that scanning and Screening, rescanning is necessary. b. Vascular dementia as defined by a HIS of =4 is exclusionary. 7. Lacks visual, auditory acuity and/or language abilities adequate to perform cognitive assessments. 8. History of any medical illness, such as cancer, requiring systemic therapy in the last 5 years, except for localized basal cell carcinoma of the skin and in-situ cervical cancer successfully treated with surgical excision; history of severe heart failure, major stroke, uncontrolled seizure disorder, or other medical illnesses that in the Investigator’s opinion will increase the patient’s risk of participation in the study or confound study assessments. 9. Patients with the following measurements identified during Screening: a. Platelet count 1.5 c. Patients with a hemorrhagic trend. 10. Positive blood screen for HIV1 and HIV2, hepatitis B surface antigen, or hepatitis C virus antibodies at Screening unless successful curative treatment for hepatitis C has been received and there is documentation that there is no hepatitis B/C virus detected 3 months after completion of treatment. 11. Any planned surgery that requires a general anesthesia that would take place during the study. Local anesthesia during outpatient surgery is permitted if, in the opinion of the Investigator, this operation does not interfere with study procedures and patient safety. 12. History or current evidence of major psychiatric illness such as schizophrenia, bipolar disorder, or MDD; or if a patient has a GDS-SF score >8 at Screening and thereby meeting criteria for MDD, then the patient will be excluded. 13. History of violent or aggressive behavior that requires medication to control. 14. Suicidal thoughts, intentions, or actions captured during screening by C-SSRS or history of suicidal attempt in 2 years prior to Screening. 15. History of alcohol or drug abuse or dependence within 12 months of screening as defined by the DSM-5. 16. Previous or ongoing treatment with Aduhelm, donanemab, or active or pas
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Assess the safety and tolerability of Trappsol® Cyclo™ over 24 weeks in patients with early Alzheimer’s disease (EAD) • Explore the potential efficacy (defined clinical effects and/or effects on biomarkers) of Trappsol® Cyclo™ over 24 weeks in patients with EAD • Determine the pharmacokinetics (PK) of Trappsol® Cyclo™ over 24 weeks in patients with EAD ;Secondary Objective: Not applicable;Primary end point(s): Safety endpoints • Incidence and severity of TEAEs • Adverse events of special interest (AESIs): - MRI assessments of ARIA-H or ARIA-E - Hearing loss based audiological examination - Infusion reactions • Vital signs and/or physical examinations • Safety clinical laboratory values (hematology, clinical chemistry, and urinalysis) including C-terminal telopeptide • 12-lead ECGs. Triplicate ECGs will be time-matched with PK samples at Week 0 (Baseline), Week 4, and Week 8. • C-SSRS PK Endpoints PK parameters including but not limited to Cmax, Tmax, AUClast, AUCinf, T½, Clast, and Tlast (see Table 10.1 in main protocol) will be calculated. Plasma levels will be measured prior to the start of the study drug infusion, 1 and 3 hours into the infusion, upon completion of infusion, 50 to 60 minutes post infusion, and 2 hours post infusion at Baseline (Week 0, V2), Week 4 (V3), Week 8 (V4), Plasma sample will be collected for potential analysis of PK trough levels will be measured prior to start of study drug infusion at Week 12 (V5) and Week 24 (V8).;Timepoint(s) of evaluation of this end point: AEs, vital signs and C-SSRS will be evaluated at every visit MRI (ARIA) will be done at Screening, Week 8, 16 and 24 Physical examination is will be done at Screening and EoT Safety clinical lab will be done at Screening, Baseline, Week 12 and EoT ECGs will be done at Screening, Baseline, Weeks 4, 8, 12 and EoT PK assessments will be done at Baseline, Week 4, 8, 12 and EoT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Mean change in total ADAS-Cog 14 score from Baseline (V2) to Weeks 12 (V5) and 24 (V8) • Change in CDR-SB from Baseline (V2) to Weeks 12 (V5) and 24 (V8) • Change in MMSE-2:SV total score from Baseline (V2) to Weeks 12 (V5) and 24 (V8) • Change in ADCS-CGIC from Baseline (V2) to Weeks 12 (V5) and 24 (V8) • Change in ADCS-ADL from Baseline (V2) to Weeks 12 (V5) and 24 (V8);Timepoint(s) of evaluation of this end point: ADAS-Cog will be done at Baseline, Weeks 12 and 24 CDR-SB, MMSE-2, ADCS-CGIC, ADCS-ADL will be done at Screening, Baseline, Weeks 12 and 24 | — |
Countries
Austria, United States
Contacts
Public ContactProject Manager
Specialized Medical Services-oncology B.V. (Allucent)
Outcome results
None listed