E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early Alzheimer’s Disease |
|
E.1.1.1 | Medical condition in easily understood language |
Early Alzheimer’s Disease |
|
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 |
|
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 |
The primary objective is to evaluate the effect of JNJ-63733657 versus placebo on clinical decline as measured by the iADRS, a composite of cognition and function |
|
E.2.2 | Secondary objectives of the trial |
Key secondary (Cognition and Function) objectives are: • To evaluate the effect of JNJ-63733657 versus placebo on cognitive decline as measured by the ADAS-Cog13 • To evaluate changes in functional status between participants treated with JNJ-63733657 or placebo as measured by the ADCS-ADL-MCI
The secondary objects are: • to evaluate the effect of JNJ-63733657 compared with placebo on cognitive decline: measured by the RBANS Total Scale Index Score • to evaluate the effect of JNJ-63733657 compared with placebo on clinical progression: measured by CDR-SB • to evluate changes in functional status between participants treated with JNJ-63733657 or placebo: measured by ADCS ADL MCI • to evaluate the effect of JNJ-63733657 on the accumulation and/or propagation of tau pathology compared with placebo: measured by tau PET
For other secondary objectives, please refer to the protocol. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each potential participant must satisfy these and all of inclusion criteria to be enrolled in the study: • 55 to 80 years of age, inclusive, at the time of initial consent. • Early AD: Gradual and progressive subjective decline in the participant’s cognition over at least the past 6 months, as reported by the participant and informant (study partner) and CDR-GS of 0.5 and memory box score ≥0.5 at screening. • Evidence of pathologic tau on a screening tau PET scan reviewed centrally by a qualified reader, as prespecified in a separate Imaging Charter. • Have a designated study partner who has adequate literacy to participate and be judged to have high likelihood of completing the study with the participant.
|
|
E.4 | Principal exclusion criteria |
Any potential participant who meets these or any of the exclusion criteria will be excluded from participating in the study: • Participants with CDR-GS ≥2 during screening or at predose baseline CDR administration. • Participants who fulfill diagnostic criteria for MCI or dementia/mild or major neurocognitive disorder suspected to be due to any etiology other than AD (eg, MCI/dementia due to frontotemporal lobar degeneration, diffuse Lewy body disease, Parkinson’s disease, cerebrovascular disease, normal pressure hydrocephalus, head injury, drug or alcohol abuse/dependence, anoxic brain injury, etc). • GDS-30 score ≥12. • HIS >4. • Known carriers of a Presenilin 1 (PSEN1), PSEN2, or Amyloid Precursor Protein mutation associated with Autosomal Dominant AD or any other neurodegenerative disease. • Medical instability or other causes for cognitive impairment that aren't AD |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from baseline on the iADRS |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At screening, on Day 1 (D1), Week 24 (W24), W52, W76, W104, W128, W156, W180, W208, W232, Early termination (ET) |
|
E.5.2 | Secondary end point(s) |
Key secondary (Cognition and Function) endpoints are: a) Change from baseline on the ADASCog13 b) Change from baseline on the ADCS-ADL-MCI The secondary endpoints are: c) Change from baseline on the RBANS Total Scale Index Score d) Change from baseline on the CDR-SB e) Change from baseline in brain tau burden, as measured by tau PET
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) At screening, on D1, W24, W52, W76, W104, W128, W156, W180, W208, W232, ET b) At D1, W24, W52, W76, W104, W128, W156, W180, W208, W232, ET c) At screening, W12, W36, W64, W88, W116, W140, W168, W192, W220, ET d) At screening, D1, W24, W52, W76, W104, W128, W156, W180, W208, W232, ET e) At screening, W52, W104, W156, W208, ET |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker assessment, Immunogenicity |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
France |
Japan |
Netherlands |
Spain |
Sweden |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 18 |