DIANTU001: Phase II/III randomized, double-blind placebo in Alzheimer's
| ISRCTN | ISRCTN90795724 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN90795724 |
| Secondary identifying numbers | 15734 |
- Submission date
- 25/02/2014
- Registration date
- 25/02/2014
- Last edited
- 16/06/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Background and study aims
Alzheimer's disease is the most common type of dementia, affecting multiple brain functions including memory. This is a study of two drugs (gantenerumab and solanezumab) in patients who are either known to have a mutation causing Alzheimer’s disease, or who don’t know their gene status but are “at risk” for an autosomal dominant Alzheimer’s disease (ADAD) mutation. The aim is to test whether one or both of these drugs prevent, delay or reverse the changes in the brain that are associated with disease symptoms in ADAD.
Who can participate?
People who are at risk of developing ADAD, aged 18-80 (and between 15 years younger to 10 years older than the age of symptom onset in their affected parent), and who are either symptom free or have mild symptoms of dementia.
What does the study involve?
Participants are randomly allocated to either the gantenerumab or solanezumab group. In the gantenerumab group, participants who are mutation carriers receive either gantenerumab or a placebo (dummy) drug by injection under the skin every 4 weeks. In the solanezumab group, participants who are mutation carriers receive either solanezumab or placebo by injection into a vein every 4 weeks. All mutation non-carriers are allocated to take the placebo. The safety and tolerability of gantenerumab and solanezumab are measured throughout the study period.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
University College London (UK)
When is the study starting and how long is it expected to run for?
January 2014 to August 2016
Who is funding the study?
1. Avid Radio Pharmaceuticals
2. Eli Lilly and Company Limited
3. Hoffman LaRoche
4. NIH (USA)
5. The Alzheimer's Association
Who is the main contact?
Jane Douglas
jane.douglas@ucl.ac.uk
Contact information
Ms Jane Douglas
Scientific
Scientific
University College London
Dementia Research Centre
Queen Square
London
WC1N 3BG
United Kingdom
| Phone | +44 (0)845 155 5000 Ext: 723560 |
|---|---|
| jane.douglas@ucl.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A Phase II/III randomized, double-blind, placebo-controlled multi-center study of two potential disease modifying therapies in individuals at risk of and with dominantly inherited Alzheimers disease |
| Study acronym | DIANTU001 |
| Study objectives | This is a study of two potential disease modifying therapies (Gantenerumab and Solanezumab) in subjects who are either known to have a mutation causing Alzheimer’s disease OR who don’t know their gene status but are “at risk” for an autosomal dominant Alzheimer’s disease (ADAD) mutation. The purpose is to test whether one or both of these drugs prevent, delay or reverse the changes in the brain that are associated with the development of disease symptoms in ADAD. |
| Ethics approval(s) | 13/SC/0535 |
| Health condition(s) or problem(s) studied | Topic: DeNDRoN; Subtopic: Dementia; Disease: Dementia |
| Intervention | 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 placebo at a 3:1 ratio. All mutation non-carriers will be randomised to placebo. Gantenerumab arm: Subjects will receive either gantenerumab or placebo via injection under the skin every 4 weeks. Solanezumab arm: Subjects will receive either solanezumab or placebo via injection of the drug into the patients vein every 4 weeks. Adverse events and serious adverse events will be reported by the investigator to the study sponsor and to regulatory bodies as required. Unblinded data on safety-related endpoints and SAEs will be reviewed quarterly by the Data Safety Monitoring Board (DSMB). Amyloid related imaging abnormalities (ARIA), which include cerebral vasogenic oedema and microhaemorrhages, are a safety endpoint. MRI scans will be analysed for ARIA changes at the Mayo clinic. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II/III |
| Drug / device / biological / vaccine name(s) | Gantenerumab, solanezumab |
| Primary outcome measure | Safety and tolerability of gantenerumab and solanezumab measured throughout the study period (104) weeks |
| Secondary outcome measures | Not provided at time of registration |
| Overall study start date | 01/01/2014 |
| Completion date | 11/08/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 80 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 10; UK Sample Size: 10 |
| Key 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 subjects 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 Alzheimers 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 |
| Key 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 subjects 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 is longer 24. Ever participated in study of an active vaccine or other long-acting biological agent which was being evaluated to prevent or postpone cognitive decline¿ Note: use of approved treatment for AD & other medications is permitted in this study in accordance with Concomitant Medications guidelines (Section 5.3 protocol). Other: 25. Lack of sufficient venous access 26. Clinically relevant abnormalities in hematology, coagulation studies or clinical chemistry 27. History of cancer in last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over past 2 years 28. Any other medical condition that could be expected to progress, recur, or change to such an extent that it could bias assessment of clinical or mental status of the subject to a significant degree or put the subject at special risk 29. Currently, or within last month prior to screening, participated in a clinical trial including a nonpharmacological trial with a key objective of improving cognition 30. Positive urine or serum pregnancy test or plan or desire to become pregnant during the course of trial. |
| Date of first enrolment | 01/01/2014 |
| Date of final enrolment | 11/08/2016 |
Locations
Countries of recruitment
- England
- United Kingdom
- United States of America
Study participating centre
University College London
London
WC1N 3BG
United Kingdom
WC1N 3BG
United Kingdom
Sponsor information
Washington University in St Louis (USA)
University/education
University/education
660 South Euclid Avenue
Campus Box 8111
Saint Louis
MO 63130
United States of America
"ROR" |
https://ror.org/01yc7t268 |
|---|
Funders
Funder type
Industry
Avid Radio Pharmaceuticals
No information available
Eli Lilly and Company
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Lilly, Eli Lilly & Company, Eli Lilly & Co., Eli Lilly And Co
- Location
- United States of America
F. Hoffmann-La Roche
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Hoffman-La Roche, F. Hoffmann-La Roche Ltd.
- Location
- Switzerland
National Institutes of Health
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Institutos Nacionales de la Salud, US National Institutes of Health, NIH
- Location
- United States of America
Alzheimer's Association
Government organisation / Associations and societies (private and public)
Government organisation / Associations and societies (private and public)
- Alternative name(s)
- Alzheimer's Disease and Related Disorders Association, Inc., Alzheimer's Disease & Related Disorders Association, Inc., AA
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
16/06/2016: Plain English summary added.
25/02/2016: Internal review - Verifying study status with principal investigator.
