A study comparing the safety and effects of a new compound, ACI-35 with placebo in patients with mild to moderate Alzheimer's disease

• Register: ISRCTN
• Last refreshed on: 17 October 2016
• Main ID: ISRCTN13033912
• Date of registration: 04/11/2015
• Prospective Registration: No
• Primary sponsor: AC Immune SA
• Public title: A study comparing the safety and effects of a new compound, ACI-35 with placebo in patients with mild to moderate Alzheimer's disease
• Scientific title: A phase Ib multicenter, double-blind, randomized, placebo-controlled study of the safety, tolerability and immunogenicity of ACI-35 in patients with mild to moderate Alzheimer's disease
• Date of first enrolment: 01/12/2013
• Target sample size: 24
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN13033912
• Study type: Interventional
• Study design: Phase Ib multi-centre double-blind randomized placebo-controlled study (Treatment)

Countries of recruitment

Finland, United Kingdom

Contacts

• Name: Eva Schier

• Name: Julian Gray

Key inclusion & exclusion criteria

Inclusion criteria: 1. Probable AD according to NINCDS-ADRDA criteria
2. Age equal to or over 60 and equal to or less than 85 years
3. Mini-Mental Status Examination (MMSE) 18 – 28 points at screening
4. Patient must be receiving a stable dose of acetylcholinesterase inhibitors for at least 3 months prior to screening
5. Patient cared for by a reliable spouse or other live-in caregiver who gives written consent to assist with clinical assessments and report safety issues
6. Patient who in the opinion of the investigator are able to understand and sign written informed consent, and to comply with all study procedures
(Note that consent must be obtained prior to conducting any trial-related procedures)
7. Women must be post-menopausal for at least one year and/or surgically sterilized
8. Female partner of male patients who are not postmenopausal or surgically sterilized must use reliable contraceptive measures e.g. double barrier contraception or hormonal contraception
Exclusion criteria: 1. MRI scan at screening which shows an alternative cause other than AD for the dementia, e.g. space occupying lesions, hydrocephalus, significant vascular disease
2. Any medical conditions other than AD which may confound the assessment of cognition performance, e.g. Parkinson’s disease, Lewy Body Dementia, vascular dementia
3. Any medical conditions (e.g. uncontrolled epilepsy, uncontrolled hypertension) which would hamper safety assessments and/or alter the ability to complete the study
4. Significant hearing or visual impairment or other issues judged relevant by the investigator preventing to comply with the protocol and to perform the outcome measures
5. Patient receiving any anticoagulant drug, or aspirin at doses greater than 100 mg daily
6. Patient receiving memantine
7. Use of tricyclic antidepressants, neuroleptics, systemic corticosteroids, immune modifying drugs including cyclosporine and mycophenolate
8. History of hemorrhagic stroke
9. History of non-hemorrhagic stroke or myocardial infarction within one year before screening
10. History of major depression, bipolar disorders, schizophrenia or other major psychiatric disorder according to DSM-5
11. History of sustained behavioural disturbances secondary to Alzheimer’s disease such as hallucinations, delusions, agitation or nocturnal behavioural disturbances
12. History of inflammatory neurology disorders including meningoencephalitis
13. History of autoimmune disease with potential for CNS involvement
14. History of cancer other than localized skin cancer within the past 5 years before screening
15. Vascular dementia according to NINDS-AIREN criteria
16. Severe infections or a major surgical operation within 3 months prior to screening
17. History of chronic or recurrent infectious or inflammatory conditions such as recurrent urinary tract infections which could hamper interpretation of safety
18. Abuse of drug or alcohol within the past five years
19. Clinically significant abnormal vital signs (including sustained sitting blood pressure greater than 160/90 mm Hg)
20. Clinically significant arrhythmias or other abnormalities on ECG at screening. (Minor abnormalities documented as clinically insignificant by the investigator will be allowed)
21. Clinically significant abnormalities of clinical haematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of SGOT, SGPT, or creatinine at screening
22. Elevated prothrombin or partial thromboplastin time at screening
23. Positive syphilis serology, Hepatitis B or C at screening
24. Vitamin B12 or folate deficiency or hypothyroidism unless on replacement therapy for at least 3 months prior screening
25. Any vaccine received within the past 2 months before screening, including influenza vaccine which if indicated must be given at least 8 weeks prior to screening
26. Previously received AD immune therapeutic agents or vaccines
27. Previously received Tau immune therapeutic agents or vaccines or investigational agents targeting Tau pathology
28. Patient anticipated to receive any vaccination other than influenza vaccine during the study
29. MRI examination cannot be done for any reason, including metal implants contraindicated for MRI studies and claustrophobia
30. Patient who has donated blood or blood products during the 30 days prior to screening or who plan to donate blood while participating in the study or within four weeks after completion of the study.

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Alzheimer's disease
Mental and Behavioural Disorders
Alzheimer's disease

Intervention(s)

Participants are randomly allocated to one of four groups using a secure interactive web based randomisation system.

Group 1: Receive a low dose of ACI-35 on a stable dosing regime of 5 administrations over a 6 month period
Group 2: Receive a medium dose of ACI-35 on a stable dosing regime of either 3 or 5 administrations over a 6 month period
Group 3: Receive a high dose of ACI-35 on a stable dosing regime of either 2 or 3 administrations over a 6 month period
Group 4: Receive a placebo on a stable dosing regime of either 2, 3 or 5 administrations over a 6 month period

In each group, this will be followed by a late booster injection about 6 months or 16 months after the initial dosing period. This will be followed by a treatment free safety follow up period of 6 months.

Primary Outcome(s)

1. Adverse events are measured by recording vital signs and completing a physical and neurological examination at each clinic visit
2. Routine haematology and biochemistry in blood and urine is measured at baseline and periodically every second or four weeks in the initial 3 months of treatment, then every 3 months until the end of the study
3. Five MRI and ECG measurements are taken during the entire study duration. Two lumbar punctures for cerebrospinal fluid (CSF) drawing are done at baseline and after one year of treatment.
4. Immunogenicity (antibody titre response against pTau) is measured using blood samples drawn at each visit and measured at specific interim analyses, after 6 and 12 months of treatment, as well as after the safety follow-up period is completed

Secondary Outcome(s)

1. Antibody titre response is measured using blood samples which are drawn at each visit and measured at specific interim analyses, after 6 and 12 months of treatment, as well as after the safety follow-up period is completed
2. Biomarkers are measured using blood samples drawn at baseline and periodically every second or four weeks in the initial 3 months of treatment, then every 3 months until the end of the study. The biomarkers will be measured at specific interim analyses, after 6 and 12 months of treatment, as well as after the safety follow-up period is completed
3. Cognitive and Clinical Effects are measured using ADAS-cog, MMSE, Trail Making Test and Fluency Tests and the Clinical Global Impression of Change Disability Assessment in Dementia and Neuropsychiatric Inventory Scale at baseline, 14, 26, 50 and 60 weeks

Secondary ID(s)

2013-000803-18

ACI-35-1201

Source(s) of Monetary Support

AC Immune SA, Janssen Pharmaceuticals, Inc.