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 a progressive disorder that causes problems with memory, thinking and behavior. Symptoms usually develop slowly and get worse over time, becoming severe enough to interfere with daily 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 | HLT |
E.1.2 | Classification code | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10074616 |
E.1.2 | Term | Prodromal Alzheimer's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 pharmacodynamic (PD) effect of a once a week (Q1W) dosing regimen of gantenerumab on brain amyloid load as determined by positron emission tomography (PET) imaging in participants with early (prodromal to mild) AD |
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E.2.2 | Secondary objectives of the trial |
• To evaluate caregiver overall satisfaction and confidence
• To assess the safety of gantenerumab in participants with early (prodromal to mild) AD
• To characterize the pharmacokinetic profile of gantenerumab using a new titration scheme and especially at the Q1W dosing frequency
• To assess the PD effect of the dosing frequency on brain amyloid |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 50-90 years old
• Probable AD dementia or prodromal AD
• Availability of a reliable study partner who accepts to participate in study procedure throughout the study duration
• Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory
• Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination score >= 22 and Clinical Dementia Rating global score of 0.5 or 1.0, as well as a clinical dementia rating memory domain score >= 0.5
• If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment
• Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche sponsored non-interventional studies
• For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug |
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E.4 | Principal exclusion criteria |
• Any evidence of a condition other than AD that may affect cognition
• History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function
• Uncontrolled hypertension
• Unstable or clinically significant cardiovascular, kidney or liver disease
• History or presence of clinically evident cerebrovascular disease, posterior reversible encephalopathy syndrome, any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent, in the opinion of the investigator, with a transient ischemic attack
• History of severe, clinically significant CNS trauma, history or presence of intracranial mass that could potentially impair cognition
• Any contraindications to brain magnetic resonance imaging
• Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
• History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits
• History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder
• At risk for suicide in the opinion of the investigator
• Alcohol and/or substance abuse or dependence within the past 2 years |
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from baseline to Week 104 in deposited amyloid as measured by brain amyloid PET Centiloid levels |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline (screening amyloid PET) to Week 104
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E.5.2 | Secondary end point(s) |
1. Responses to Caregiver questionnaire up to Week 104
2. Nature, frequency, severity, and timing of adverse events and serious adverse events
3. Physical examinations, vital signs, blood tests, ECGs, and Columbiaï€Suicide Severity Rating Scale
4. Nature, frequency, severity, and timing of MRI findings: amyloid-related imaging abnormalities-edema/effusion; amyloid-related imaging abnormalities-hemosiderin deposition
5. Nature, frequency, severity, and timing of injection site reactions
6. Presence of anti-drug antibody (ADAs) during the study relative to the presence of ADAs at baseline
7. Plasma concentration of gantenerumab at specified timepoints
8.The influence of dosing frequency information on the performance of a quantitative PK-PD model developed based on PK and PET from this and previous studies
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to Week 104
2-7. Baseline up to end of study (Week 120)
8. At Week 104 |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Belgium |
Germany |
Italy |
Poland |
Spain |
United Kingdom |
United States |
France |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end of the study is defined as the date when the last participant, last visit occurs or the date at which the last data point required for statistical analysis or safety follow-up is received for the last participant, whichever occurs later. |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 16 |