Alzheimer's disease MedDRA version: 17.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Copegus
Product Name: ribavirin
Pharmaceutical Form: Capsule
INN or Proposed INN: 1-beta-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide
CAS Number: 36791-04-5
Other descriptive name: RIB
Sponsors
Apodemus AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients diagnosed with AD according to ICD-10 2. 60–85 years at the time of screening 3. Mini Mental State Exam score 21–27 and judged by the Investigator to be able to give informed consent 4. Patients have adequate hearing, vision, and language skills to perform neuropsychiatric testing and interviews as specified in the protocol, as judged by the Investigator 5. 12-lead ECG with normal tracings; or changes that are not clinically significant and do not require medical intervention, as judged by the Investigator 6. Patient has a relative or caregiver, judged to be reliable by the Investigator, who has signed informed consent. The relative or caregiver should participate in the patient’s visits at the clinic and assist the patient with drug compliance. 7. Willingness to participate after signing informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: 1. Active hepatitis B, active hepatitis C, or HIV infection 2. Serious cardiac disease including unstable or uncontrolled cardiac disease during the last 6 months and/or previous history of deep vein thrombosis or clinical signs of deep venous thrombosis 3. Major surgical procedure within 4 weeks prior to inclusion 4. Patients on unstable treatment with AChI and / or Memantine for dementia. Unstable treatment is defined as initiated treatment or changed treatment or dose within 3 months prior to the baseline visit (i.e. patients on stable AChI / Memantine treatment and patients without AChI / Memantine treatment can be included in the trial) If patients receive treatment with AChI for dementia this treatment should have been unchanged regarding drug(s) and dose(s) for at least 3 months prior to the baseline visit (patients on an unchanged AChI dose/medication and patients without AChI treatment can be included in the trial) 5. Men without reliable contraceptive method if sexually active with WOCBP. For purposes of this trial, WOCBP include any female who has experienced menarche, who has not undergone tubal ligation, and who is not postmenopausal. Post menopause is defined as: amenorrhea = 12 consecutive months without another cause. 6. Participation in any other clinical trial within 30 days of inclusion (randomisation) in the trial or patients with unresolved investigational treatment-related adverse events 7. Other chronic disease or previous organ transplantation judged by the Investigator to interfere with the assessment of treatment success and/or ability to fully participate in the trial 8. Impaired kidney function with a glomerular filtration rate (GFR) calculated from cystatin C <60 mL/min 9. Calculated ribavirin dose at screening is <600 mg/day* according to the following formula: 0.244 x 10ax 24b x (0.122 x GFR + 0.0414 x body weight in kg) when a Target concentration=10 mmol/L and b Dosing frequency=24 hours * If the ribavirin/placebo starting dose is adjusted to 400mg/day the calculated ribavirin dose may be <600mg/day, but must not be <400mg/day at screening. 10. Known blood disease or Anaemia Haemoglobin < 120g/L for women and <130 g/L for men 11. Known haemoglobinopathy (e.g. thalassemia and sickle cell anaemia) 12. Patients that require immunosuppressive treatments including azathioprin, ciclosporin, systemic steroid treatment (e.g. prednisolone at doses of =10 mg/day or hydrocortisone) or has received such treatment within the last 6 months prior to randomization 13. Patients that are treated with drugs that can interact significantly with APO-P001; ethinylestradiol and/or ribavirin; azathiopin, didanosine, zidovudine, mercaptopurine, stavudine 14. Lack of suitability for participation in the trial, for any reason, as judged by the Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main efficacy objective:• To investigate the effect of Apovir on disease progression of AD as assessed by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale [ADAS-cog] compared to placebo Main safety objective: • To investigate the safety and tolerability of the combination therapy of Apovir in patients with AD ;Secondary Objective: • To investigate the effect of Apovir on disease progression of AD assessed by cognitive tests – (Mini Mental State Examination [MMSE], ADAS-cog, Alzheimer’s Quick Test [AQT] and Clinical Dementia Rating [CDR]) • To investigate the plasma and cerebrospinal fluid concentrations of Apovir (APO-P001 and ribavirin) in patients with AD ;Primary end point(s): Main efficacy endpoint:• ADAS-cog at 9 months (visit 7) Main safety endpoint: • Frequency and intensity of adverse events;Timepoint(s) of evaluation of this end point: Efficacy endpoint: at 9 months Safety endpoint: total duration of the original part of the trial (visits 1 to 8) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Tolerability of Apovir as assessed by dose adjustments, interruption- or discontinuation of treatment • Vital signs, laboratory parameters and weight Change in disease progression of AD as assessed by: • ADAS-cog at 3 months (visit 5), and 6 months (visit 6) and the 1-month follow-up visit (visit 8) • AQT at 3 months (visit 5), 6 months (visit 6), and 9 months (visit 7) and the follow-up visit • MMSE at 6 months (visit 6), and 9 months (visit 7) and the follow-up visit • CDR sum of boxes at 9 months (visit 7) and the follow-up visit Plasma concentrations of Apovir: • Plasma concentrations Cpre dose of Apovir (APO-P001 and ribavirin respectively) on day 28 (visit 4) and at 3 months (visit 5), 6 months (visit 6) and 9 months (visit 7) (concentrations at 3 months will be compared to published data [Rhodes and Liu 2001; Khakoo et al 1998]) Cerebrospinal fluid concentrations of Apovir: • Cerebrospinal fluid concentrations of Apovir (APO-P001 and ribavirin respectively) at 9 months (visit 7) ;Timepoint(s) of evaluation of this end point: Timepoints of evaluation of all safety endpoints is total duration of the original part of the trial (visits 1 to 8). Timepoints for evaluation of efficacý endpoints is listed in the respective endpoint | — |
Countries
Sweden
Contacts
Public ContactClinical trials
Apodemus AB
Outcome results
None listed