Alzheimer's Disease
Conditions
Brief summary
To evaluate the safety and tolerability of ascending oral doses of CHF 5074 administered once per day for up to 12 weeks to patients with mild cognitive impairment.
Interventions
DRUGCHF 5074 1x
oral tablet, 1x, once a day in the morning for 12 weeks
DRUGCHF 5074 2x
oral tablet, 1x, once a day in the morning for 4 weeks, followed by oral tablet, 2x, once a day in the morning for 8 weeks
DRUGCHF 5074 3x
oral tablet, 1x, once a day in the morning for 4 weeks, followed by oral tablet, 2x, once a day in the morning for 4 weeks, followed by oral tablet, 3x, once a day in the morning for 4 weeks
DRUGPlacebo
oral tablet, once a day in the morning for 12 weeks
Sponsors
CERESPIR
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of amnestic or non-amnestic Mild Cognitive Impairment. * Mini-Mental State Examination score higher than 24 at screening. * MRI scan of the brain at screening with fluid-attenuation inversion recovery (FLAIR) and T2\*-weighted gradient-recalled-echo (GRE) sequences.
Exclusion criteria
* Diagnosis of Alzheimer's disease according to the (DSM-IV-TR) or NINCDS-ADRDA criteria. * Any medical condition that could explain the patients cognitive deficits. * CT or MRI brain imaging results obtained within 12 months prior to baseline showing evidence of infection, infarction, or focal lesions of clinical significance * MRI scan at screening showing more than 4 cerebral microhemorrhages (lesions with diameter ≤ 10 mm). * Geriatric Depression Scale (30-point scale) score \> 9 at screening. * History of stroke. * Modified Hachinski ischemic scale score \> 4 at screening. * Women of childbearing potential. * Vitamin B12 or folate deficiency. * Diagnosis of schizophrenia or recurrent mood disorder (including unipolar and bipolar disorders) within 3 years of screening. * Current diagnosis of peptic ulcer or gastrointestinal bleeding within the last year and/or chronic inflammatory bowel disease. * Concomitant use of donepezil at doses \> 5 mg/day or other cholinesterase inhibitors (rivastigmine or galantamine) at any dose. * Concomitant use of memantine at dose \> 20 mg/day. * Concomitant use of psychoactive drugs (sedatives, hypnotics, etc).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in ∆sCD40L Levels Between CHF 5074 Doses and Placebo at Any Specific Time Point | up to 12 weeks | To assess if there were differences in ΔsCD40L levels between CHF 5074 doses and placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of Trough CHF 5074 Plasma Levels | Days 85 | evaluate the pharmacokinetics (PK) of CHF 5074 in patients with MCI. |
| Changes in Plasma ΔTNFα Concentrations | 29 days | — |
Countries
Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CHF 5074 1x oral tablet, multidose
CHF 5074 1x: oral tablet, 1x, once a day in the morning for 12 weeks | 24 |
| CHF 5074 2x oral tablet, multidose
CHF 5074 2x: oral tablet, 1x, once a day in the morning for 4 weeks, followed by oral tablet, 2x, once a day in the morning for 8 weeks | 24 |
| CHF 5074 3x oral tablet, multidose
CHF 5074 3x: oral tablet, 1x, once a day in the morning for 4 weeks, followed by oral tablet, 2x, once a day in the morning for 4 weeks, followed by oral tablet, 3x, once a day in the morning for 4 weeks | 24 |
| Placebo placebo, oral tablet, multidose
Placebo: oral tablet, once a day in the morning for 12 weeks | 24 |
| Total | 96 |
Baseline characteristics
| Characteristic | CHF 5074 1x | CHF 5074 2x | CHF 5074 3x | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67.7 years STANDARD_DEVIATION 8.1 | 68.9 years STANDARD_DEVIATION 8.5 | 69.0 years STANDARD_DEVIATION 9.2 | 68.1 years STANDARD_DEVIATION 8 | 68.4 years STANDARD_DEVIATION 8.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 22 Participants | 24 Participants | 23 Participants | 92 Participants |
| Region of Enrollment Italy | 0 participants | 0 participants | 5 participants | 0 participants | 5 participants |
| Region of Enrollment United States | 24 participants | 24 participants | 19 participants | 24 participants | 91 participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 11 Participants | 8 Participants | 40 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 13 Participants | 16 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 24 | 18 / 24 | 11 / 24 | 7 / 24 |
| serious Total, serious adverse events | 2 / 24 | 2 / 24 | 1 / 24 | 1 / 24 |
Outcome results
Primary
Differences in ∆sCD40L Levels Between CHF 5074 Doses and Placebo at Any Specific Time Point
To assess if there were differences in ΔsCD40L levels between CHF 5074 doses and placebo
Time frame: up to 12 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 5074 1x | Differences in ∆sCD40L Levels Between CHF 5074 Doses and Placebo at Any Specific Time Point | 270.28 pg/ml | Standard Error 371.09 |
| CHF 5074 2x | Differences in ∆sCD40L Levels Between CHF 5074 Doses and Placebo at Any Specific Time Point | 403.22 pg/ml | Standard Error 377.79 |
| CHF 5074 3x | Differences in ∆sCD40L Levels Between CHF 5074 Doses and Placebo at Any Specific Time Point | -1293.42 pg/ml | Standard Error 362.69 |
| Placebo | Differences in ∆sCD40L Levels Between CHF 5074 Doses and Placebo at Any Specific Time Point | 242.49 pg/ml | Standard Error 361.32 |
Secondary
Changes in Plasma ΔTNFα Concentrations
Time frame: 29 days
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 5074 1x | Changes in Plasma ΔTNFα Concentrations | 2.57 pg/ml | Standard Error 1.1 |
| CHF 5074 2x | Changes in Plasma ΔTNFα Concentrations | -0.339 pg/ml | Standard Error 1.09 |
| CHF 5074 3x | Changes in Plasma ΔTNFα Concentrations | -1.568 pg/ml | Standard Error 1.05 |
| Placebo | Changes in Plasma ΔTNFα Concentrations | 0.039 pg/ml | Standard Error 1.05 |
Secondary
Measurement of Trough CHF 5074 Plasma Levels
evaluate the pharmacokinetics (PK) of CHF 5074 in patients with MCI.
Time frame: Days 85
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 5074 1x | Measurement of Trough CHF 5074 Plasma Levels | 5497 ng/ml | Standard Deviation 4940 |
| CHF 5074 2x | Measurement of Trough CHF 5074 Plasma Levels | 7882 ng/ml | Standard Deviation 8231 |
| CHF 5074 3x | Measurement of Trough CHF 5074 Plasma Levels | 19999 ng/ml | Standard Deviation 17474 |