Alzheimer's disease
Conditions
Interventions
Product Name: CPHPC
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: CPHPC
CAS Number: 224624-80-A
Other descriptive name: hexanoyl bis(D)-proline
GSK2315698
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-g/ml
Pharmaceutical form of the placebo: Injection
Route of administration of the place
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) A clinical diagnosis of mild AD (MMSE 20-28 inclusive);. (2) Male or female between 50 – 85 years of age (inclusive); (3) Supportive evidence of AD pathology from at least one of the following: MRI brain scan consistent with a diagnosis of AD or florbetapir (18F) PET imaging consistent with a diagnosis of AD. (4) Participant must live with a partner, relative or carer who can both attend appointments and assist with dosing of medication by s.c. injection; (5) Agree to undergo MRI and PET imaging, and lumbar puncture; (6) Ability to provide written informed consent; (7) Women of child bearing potential and males with a partner of child bearing potential willing to use effective contraception for the duration and 30 days post completion of trial treatment; (8) In the opinion of the CI or delegate, adequate understanding of written and verbal information in English Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: (1) Ongoing clinically significant depression, in the opinion of the PI likely to impede completion of the trial, or other diseases or drugs influencing cognition; anti-depressant medication stable for more than 3 months is acceptable; (2) Significantly abnormal renal (eGFR <50mls/min/m2) or hepatic enzyme values two fold or greater above the upper limit of the reference range; (3) Current use of warfarin, rivaroxaban, apixaban and or dabigatran; low dose aspirin or clopidogrel are permitted. (4) Current use of cholinesterase inhibitors or memantine unless maintained on a stable dose for at least 3 months prior to randomisation; (5) Use of other experimental drugs within 3 months of randomisation; (6) Pregnancy or lactation* (current, or planned in the next 13 months). *the safety of CPHPC in pregnancy is unknown. Teratogenicity risks for female partners of males being treated with CPHPC are unknown. (7) Any medical condition that could be expected to progress, recur, or change to an extent that it could bias the assessment of the clinical or mental status of the participant to a significant degree or put the participant at special risk in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the safety, tolerability and potential effectiveness of 52 weeks exposure to CPHPC (investigational product) compared to placebo for the treatment of Alzheimer’s disease. ;Secondary Objective: Explore the effects of CPHPC on the whole brain, especially the hippocampus using volumetric MRI scans at baseline and 12 months Assess any effects of CPHPC on cognition via neurological testing MRI at baseline and 12 months to observe any disease modification from CPHPC Amyloid Pet-CT to observe levels of amyloid deposit in the brain at baseline and 12 months to find if there will be any difference in levels between treatment arms Explore spinal fluid SAP concentrations via lumbar puncture to assess any effects between each treatment arm Plasma SAP concentration at 0, 3, 6, 9, 12 and 13 months Optional TMS to provide extra information on the effects of CPHPC and SAP depletion on the synaptic function of the brain;Primary end point(s): Consolidated evidence of safety and tolerability of CPHPC as determined by absence of: adverse events, worsened cognition, behavioural changes or MRI changes.;Timepoint(s) of evaluation of this end point: Determined by absence of: adverse events, worsened cognition, behavioural changes or MRI changes - all of these will be assessed throughout the trial at trial visits and engagement calls with the trial team. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The time points are specified in detail as described under 'secondary end point(s)' 23-2;Secondary end point(s): 1. Rates of whole brain and hippocampal atrophy using quantitative semi-automated analysis of volumetric MRI of brain scans obtained at baseline and 12 months. 2. Cognition: A version of the Preclinical Alzheimer Cognitive Composite (PACC), which is a composite score comprising: Face Name Associative Memory Performance, Wechsler Logical Memory (paragraph recall), Mini Mental State Examination (MMSE) and Digit Symbol Substitution Test score from the Wechsler Adult Intelligence Scale–Revised; verbal fluency; an in-house computer-based reaction time task; Clinical Dementia Rating (CDR), and Neuropsychiatric Inventory (NPI). The tests will be performed at 0, 6, 12, and 13 months. 3. Other qualitative and quantitative MRI parameters in addition to volumetric MRI sequence obtained at 0 and 12 months including T2, FLAIR, T2*, multi-parametric mapping (MPM), diffusion tensor imaging and magnetization transfer (MT) and proton density. These parameters provide high-resolution maps of grey and white matter microstructure, and so can serve as a biomarker of disease modification by CPHPC. 4. Amyloid PET-CT: florbetapir (18F) PET-CT by single intravenous dose and scanning at the Institute of Nuclear Medicine, UCLH at 0 (or within the previous 4 weeks), and 12 months. 5. Lumbar puncture: CSF concentrations of SAP, CPHPC, Aß1-42, total and phosphorylated t at 0 and 12 months. 6. Plasma SAP concentration at 0, 3, 6, 9, 12 and 13 months. 7. Optional transcranial magnetic stimulation (TMS): (i) theta burst protocol to assess synaptic plasticity; (ii) cholinergic short afferent inhibition protocol at 0, 1, 12 and 13 months. | — |
Countries
United Kingdom
Contacts
Public ContactChinaza Ezirim
University College London
Outcome results
None listed