E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
AD is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate the efficacy of RO7105705 compared with placebo •To evaluate the safety and tolerability of RO7105705 compared with placebo
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E.2.2 | Secondary objectives of the trial |
•To evaluate the effect of RO7105705 on cognition compared with placebo •To evaluate the effect of RO7105705 on activities of daily living compared with placebo •To characterize the pharmacokinetics of RO7105705 •To evaluate the immune response to RO7105705
Exploratory objective •To evaluate the effect of RO7105705 on pathological burden of tau, using tau PET imaging
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age between 50 and 80 years - National Institute on Aging/Alzheimer’s Association core clinical criteria for probable AD dementia or mild cognitive impairment (prodromal AD) - Evidence of the AD pathological process, by a positive amyloid assessment either on cerebrospinal fluid Aβ1−42 OR amyloid positron emission tomography (PET) scan. Historical amyloid PET scans may be accepted in some cases - Mild AD symptomatology, as defined by a screening Mini-Mental State Examination score of >= 20 points and Clinical Dementia Rating (CDR) −Global Score of 0.5 or 1 - Abnormal memory function at screening - Availability of a person with sufficient contact with the patient to be able to provide accurate information on the patient’s cognitive and functional ability |
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E.4 | Principal exclusion criteria |
- Pregnant or breastfeeding - Inability to tolerate magnetic resonance imaging (MRI) procedures or contraindication to MRI - Able to undergo either PET imaging or lumbar dural puncture, or both, and patients with contraindications to both procedures are ineligible - Residence in a skilled nursing facility - Any serious medical condition or abnormality in clinical laboratory tests that remains abnormal on retest and, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study, or bias the assessment of the clinical or mental status of the participant to a significant degree - Any evidence of a condition other than AD that may affect cognition - Substance abuse meeting criteria for alcohol, cannabis, phencyclidine, other hallucinogen, inhalant, opioid, sedative, hypnotic, anxiolytic, or stimulant use disorder of any severity (per the Diagnostic and Statistical Manual of Mental Disorders, Version 5) within the past 2 years - Use of any experimental therapy within 90 days or 5 half-lives prior to screening, whichever is greater and any passive immunotherapy (immunoglobulin) against tau, except use of RO7105705 in Genentech Study GN39058, as long as the last dose was at least 90 days prior to screening - Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was at least 1 year prior to screening and any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline - Any previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other neurodegenerative disorder within 1 year of screening - Systemic immunosuppressive therapy within 12 months of screening through the entire study period - Typical antipsychotic or neuroleptic medication within 6 months of screening - Daily treatment with any of the following classes of medication, except for intermittent short-term use, which is permitted except within 2 days or 5 half-lives (whichever is longer) prior to any COA such as atypical antipsychotics, Opiates or opioids ,Benzodiazepines, barbiturates, or hyponotics and any medication with centrally-acting antihistamine or anticholinergic activity - Stimulant medications, unless the dose has been stable within the 6 months prior to screening and is expected to be stable throughout the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from baseline on the CDR−Sum of Boxes 2. Nature, frequency, severity, and timing of adverse events and serious adverse events. 3. Changes from baseline in vital signs, physical findings, neurologic findings, ECG, and clinical laboratory results during and following RO7105705 administration 4. Nature, frequency, severity, and timing of neuroimaging abnormalities 5. Changes from baseline in suicidal ideation and behavior during and following RO7105705 administration |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline to Week 73, Baseline to 39 months if participating in the OLE 2-5. Baseline to Week 81, Baseline to 42 months if participating in the OLE |
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E.5.2 | Secondary end point(s) |
1. Change from baseline on the RBANS 2. Change from baseline on the Alzheimer’s disease Assessment Scale−Cognitive Subscale 13 3. Change from baseline on the Amsterdam Instrumental Activity of Daily Living questionnaire 4. Change from baseline on the Alzheimer’s disease Cooperative Study Group−Activities of Daily Living Inventory 5. Serum concentrations of RO7105705 at specified timepoints 6. Presence of anti-drug antibody during the study relative to their presence at baseline
Exploratory endpoint 1. Change from baseline in brain tau burden as measured by [18F] GTP1 PET |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4. Baseline to Week 73, Baseline to 39 months if participating in the OLE 5-6. Baseline to Week 81, Baseline to 42 months if participating in the OLE
Exploratory Timepoint 1. Baseline to Week 73, Baseline to 39 months if participating in the OLE
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
Denmark |
Finland |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |