Trial Outcomes & Findings for A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD) (NCT NCT04592341)

Last Updated: 2024-03-27

Results Overview

Screening amyloid PET scan was considered baseline evaluation.Brain amyloid load was quantified in terms of Standardized Uptake Value Ratio (SUVR),defined as ratio of tracer uptake in cortical composite target region of interest(ROI)to tracer uptake in reference ROI.Composite region: frontal,parietal,temporal,posterior cingulate cortex,anterior cingulate cortex. Reference ROI (whole cerebellum) was represented by weighted average of Cerebellum Ventral,Cerebellum Dorsal (left/right), Cerebellar White Matter.SUVR linearly transformed to standardized Centiloid Scale (CL) using formula CL=175.6xSUVR-174.2.CL ranges from \<0 to \>100, anchor points are 0=high-certainty amyloid negative scan and 100=amount of global amyloid deposition found in typical AD scan.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

192 participants

Primary outcome timeframe

Baseline, Week 104

Results posted on

2024-03-27

Participant Flow

Participants took part in this study at 33 investigative centers in the United States, Poland, Spain, Belgium, France, Germany, Italy, and the United Kingdom from 18 November 2020 up to 15 March 2023.

This was a single-arm study and all participants received gantenerumab according to predefined universal up-titration scheme as follows: 120 mg every 4 weeks (Q4W) (Day 1, Week (W) 4, and W8), then 255 mg Q4W (W 12, 16, and 20), then 255 mg Q2W for 12 weeks (W 24, 26, 28, 30, 32, and 34), followed by target dose of 255 mg Q1W (W 36 to 104). Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.

Participant milestones

Participant milestones
Measure	Gantenerumab Participants received gantenerumab, subcutaneous (SC) injections with gradual up-titration starting at a dose of 120 mg, every 4 weeks (Q4W) on Day 1, Week 4, and Week 8, then 255 mg, Q4W on Weeks 12, 16, and 20, and then 255 mg every 2 weeks (Q2W) for 12 weeks (Weeks 24, 26, 28, 30, 32, and 34), followed by 255 mg every week (Q1W) up to Week 104 (Weeks 36 to 104).
Overall Study STARTED	192
Overall Study COMPLETED	116
Overall Study NOT COMPLETED	76

Reasons for withdrawal

Reasons for withdrawal
Measure	Gantenerumab Participants received gantenerumab, subcutaneous (SC) injections with gradual up-titration starting at a dose of 120 mg, every 4 weeks (Q4W) on Day 1, Week 4, and Week 8, then 255 mg, Q4W on Weeks 12, 16, and 20, and then 255 mg every 2 weeks (Q2W) for 12 weeks (Weeks 24, 26, 28, 30, 32, and 34), followed by 255 mg every week (Q1W) up to Week 104 (Weeks 36 to 104).
Overall Study Physician Decision	5
Overall Study Study Terminated by Sponsor	5
Overall Study Withdrawal by Subject	53
Overall Study Lost to Follow-up	3
Overall Study Death	1
Overall Study Adverse Event	5
Overall Study other	4

Baseline Characteristics

A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gantenerumab n=192 Participants Participants received gantenerumab, SC injections with gradual up-titration starting at a dose of 120 mg, Q4W on Day 1, Week 4, and Week 8, then 255 mg, Q4W on Weeks 12, 16, and 20, and then 255 mg Q2W for 12 weeks (Weeks 24, 26, 28, 30, 32, and 34), followed by 255 mg Q1W up to Week 104 (Weeks 36 to 104).
Age, Continuous	70.5 years STANDARD_DEVIATION 8.1 • n=5 Participants
Sex: Female, Male Female	97 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	179 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	176 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 104

Population: ITT population set, included all enrolled participants (i.e., who gave informed consent, did not fail screening, and had at least one Amyloid PET scan with a valid quantitative measurement performed with either florbetaben or flutemetamol), whether or not the participant received the assigned treatment. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Outcome measures
Measure	Gantenerumab n=192 Participants Participants received gantenerumab, subcutaneous (SC) injections with gradual up-titration starting at a dose of 120 mg, every 4 weeks (Q4W) on Day 1, Week 4, and Week 8, then 255 mg, Q4W on Weeks 12, 16, and 20, and then 255 mg every 2 weeks (Q2W) for 12 weeks (Weeks 24, 26, 28, 30, 32, and 34), followed by 255 mg every week (Q1W) up to Week 104 (Weeks 36 to 104).
Change From Baseline in Brain Amyloid Load at Week 104 as Measured by [18F] Florbetaben Positron Emission Tomography (PET) Scan Baseline	101.80 centiloid Standard Deviation 29.80
Change From Baseline in Brain Amyloid Load at Week 104 as Measured by [18F] Florbetaben Positron Emission Tomography (PET) Scan Change from Baseline at Week 104	-35.48 centiloid Standard Deviation 16.39

SECONDARY outcome

Timeframe: Weeks 36, 52, 76, 104

Population: Opportunity for Home Dosing Safety-Evaluable Analysis Set (OH-SE) included all participants of the SE analysis set who did not discontinue the study drug before week 26. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

HAQ comprised 4 items completed by study partner capturing confidence (Q1), convenience (Q2), ease of use (Q3), and overall satisfaction (Q4) with administering medication. Response options Q1: Not at all confident, somewhat confident, confident, very confident; Q2: Not at all convenient, somewhat convenient, convenient, very convenient; Q3: Not at all easy, somewhat easy, easy, very easy; Q4:Not at all satisfied, somewhat satisfied, satisfied, very satisfied.