Topic: DeNDRoN
Conditions
Interventions
Participants will be randomised 1:1 to either the gantenerumab or solanezumab arm of the study. Within each treatment arm, subjects who are mutation carriers will be randomised to active treatment or
Sponsors
Washington University in St Louis (USA)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject may be included if the answer to all of the following statements is ?yes?: 1. Written consent is signed and dated by the subject, Study Partner (if applicable) and/or by the subject?s legally acceptable representative according to local regulations for both the core trial ICF and the drug-specific ICF 2. Subject is 18-80 years of age (inclusive) 3. For women able to have children, the subject must agree to use effective contraceptive measures (e.g., hormonal contraception, intrauterine device, sexual abstinence, barrier method with spermicide) if partner is not sterilised. Men must agree to use effective contraceptive measures 4. Mutation status 4.1. Subject is a carrier 1 of a mutation in PSEN1, APP or PSEN2 gene that is associated with dominantly inherited Alzheimer?s disease 2 OR at 50% risk for such a mutation (e.g. does not know their mutation status AND is a child or sibling of known mutation carrier) 4.2. Subject is within 15 to +10 years of the age of cognitive symptom onset in the affected parent (refer to Manual of Operations for calculation of estimated age of onset). 4.3. Subjects who are aware that they are mutation negative are not eligible for enrolment. 5. Cognitively normal or with mild cognitive impairment or mild dementia, CDR 01 (inclusive) 6. Fluency in DIAN trial approved language and evidence of adequate pre-morbid intellectual functioning 7. Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments 8. Receiving stable doses of medication(s) for the treatment of non-excluded medical condition(s) for at least 30 days prior to baseline visit (V2) with the exception of medications taken for episodic conditions (e.g., migraine abortive therapy, antibiotics and other medications for upper respiratory and gastrointestinal ailments), AND, if treated with cholinesterase inhibitors and/or memantine, all of the following conditions are also met: 8.1. The subject has been maintained on a stable dose regimen for at least 90 days prior to screening¿ 8.2. The subject is free of any clinically important side effects attributable to the drug. Side effects that are intermittent, stable or well-tolerated by the subject are not exclusionary. 9. Has a Study Partner who in the investigator's judgment is able to provide accurate information as to the subject's cognitive and functional abilities, who agrees to provide information at the study visits which require study partner input for scale completion, and who signs the necessary consent form if applicable 10. Agrees not to donate blood or blood products for transfusion for the duration of the study and for one year after the final dose of study drug 11. In the opinion of the investigator, the subject will be compliant and have a high probability of completing the study
Exclusion criteria
Exclusion criteria: Subject will be excluded if answer to any of following statements is ?yes?. CNS Disorder 1. Significant neurologic disease (other than AD) or psychiatric disease that may currently or during the course of study affect cognition or subject?s ability to complete study. 2. At high risk for suicide. Current stable mild depression or current use of antidepressant medications is not exclusionary. 3. History of clinically evident stroke or history of clinically important carotid or vertebrobasilar stenosis, plaque, or other prominent risk factor for stroke or cerebral hemorrhage. Low dose aspirin (= 325 mg daily) is not exclusionary. 4. Alcohol or drug dependence sufficient to meet DSM-IV criteria currently or in past 1 year. Imaging related exclusion criteria 5. History of or baseline visit brain MRI scan indicative of other significant abnormality Note: For subjects who have participated in the DIAN observational study, site staff should work with DIAN Observational Imaging Core to review results of MRIs done in the observational study so that those with pre-existing exclusionary findings on MRI are not unnecessarily subjected to screening & baseline visit procedures. 6. Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in eyes, skin or body which would preclude MRI scan. Cardiovascular Disorders 7. Uncontrolled hypertension within 6 months prior to screening 8. Myocardial infarction or other myocardial ischemic events in last 2 years 9. Heart failure resulting in limitation of physical activity 10. History of atrial fibrillation except if only episode which resolved more than three years ago & which treatment is no longer indicated 11. 12-lead ECG: Clinically significant abnormalities in subjects over 65 years of age. A discrepancy between local & central read will not be considered a protocol deviation. Hepatic/Renal Disorders 12. Alanine aminotransferase (ALT) = 2 times the upper limit of normal or aspartate aminotransferase (AST) = 3 times the upper limit of normal or baseline total bilirubin = 2 times the upper limit of normal 13. Creatinine clearance lower than 30 mL/min according to Cockcroft-Gault formula (if confirmed at retest) 14. Clinical significant abnormalities in urinalysis. Infections/Immune Disorders 15. History of Human Immunodeficiency Virus infection, history of Hepatitis B infection within past year, history of Hepatitis C infection which has not been adequately treated or history of spirochete infection of central nervous system 16. Allergies to humanised monoclonal antibodies or to components of formulations of these antibodies 17. Treatment with immunosuppressive medications within 90 days prior to baseline visit or chemotherapeutic agents for malignancy in last 3 years. Metabolic/Endocrine Disorders 18. Current clinically significant abnormalities of thyroid function studies, clinically significant deficiency in B12 19. Screening HgbA1C >8% (retesting is permitted if slightly elevated) or poorly controlled insulindependent diabetes. Subject may be rescreened after 3 months to allow optimisation of diabetic control 20. Morbid obesity with significant comorbidities or would preclude MRI imaging. Co-Medications 21. Anticoagulants except low dose (= 325 mg) aspirin 22. Have been exposed to monoclonal antibody targeting beta amyloid peptide in past six months 23. Received any other investigational treatment within 3 months of screening or 5 half-lives whichever
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of gantenerumab and solanezumab measured throughout the study period (104) weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Not provided at time of registration | — |
Countries
United Kingdom, United States of America
Outcome results
None listed