Alzheimer Disease
Conditions
Brief summary
The main purpose of the study was to evaluate the safety and tolerability of long-term administration of gantenerumab in participants with AD. All participants who have completed the open-label extensions (OLEs) of studies WN25203 or WN28745 were enrolled in Part 1 of this study. Of these, participants who completed Week 104 visit in Part 1. Participants received open-label gantenerumab by subcutaneous (SC) injection every four weeks (Q4W) at the same dose as administered in the parent studies (part 1)/ Week 104 visit.
Interventions
DRUGGantenerumab
Gantenerumab was administered as SC injection Q4W.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Part 1: Participants who completed the open-label extensions (OLEs) of studies WN25203 or WN28745 will be eligible to participate in Part 1 of the study * Part 2: All participants who have completed Week 104 visit in Part 1 will be eligible for Part 2 of the study * For Part 1 and Part 2: * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) 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 last dose of study drug * Agreement to not donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug * Availability of a person ('caregiver') who in the investigator's judgement, has frequent and sufficient contact with the participant
Exclusion criteria
* Prematurely discontinued from the OLEs of studies WN25203 or WN28745 or from study drug for any reason * Any medical condition that may jeopardize the participant's safety if he or she continues to receive study treatment * If the participant is unlikely to benefit from gantenerumab therapy, based on disease progression or other factors, or if study participation is otherwise not in the participant's best interest * Any investigational treatment other than gantenerumab during or since completion of the OLEs of studies WN25203 or WN28745 * Pregnancy * Evidence of disseminated leptomeningeal hemosiderosis (i.e., more than three focal leptomeningeal hemosiderosis) * Evidence of intracerebral macrohemorrhage * Part 2: Participants who have been discontinued from Part 1 of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133) | An AE was defined as any untoward medical occurrence in a participant administered with gantenerumab and which does not necessarily have a causal relationship with gantenerumab. A Serious Adverse Event (SAE) is any significant hazard, contraindication, side effect that is fatal or life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is medically significant or requires intervention to prevent one or other of the outcomes listed above, and which does not necessarily have a causal relationship with gantenerumab. |
| Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline (Day 1), up to Week 104 | C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, & attempts with actual/potential lethality. Categories have binary responses (yes/no) & include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a yes answer to any of the listed categories. Score of 0= no suicide risk present. Score of 1 or higher= suicidal ideation/behavior. Number of participants with any suicidal ideation/behavior were reported. |
| Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) AEs | Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133) | — |
| Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) AEs | Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133) | — |
| Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab | Up to Week 133 | — |
| Number of Participants With Injection-Site Reactions | Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133) | — |
| Number of Participants Who Discontinued Treatment Due to AEs | Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133) | An AE was defined as any untoward medical occurrence in a participant administered with gantenerumab and which does not necessarily have a causal relationship with gantenerumab. SAE is any significant hazard, contraindication, side effect that is fatal or life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is medically significant or requires intervention to prevent one or other of the outcomes listed above, and which does not necessarily have a causal relationship with gantenerumab. |
Countries
Argentina, Australia, Canada, Chile, Denmark, Italy, Japan, Mexico, Netherlands, Poland, Russia, South Korea, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants took part in Part 1 of the study at 56 centers in the United States, Spain, Canada, Italy, Germany, Japan, Korea, Mexico, Poland, Turkey, Australia, Russia, Argentina, Switzerland, Chile, Denmark, and Netherlands from 22 May 2020 to 04 Jan 2023. The study was terminated before Part 2 was initiated.
Pre-assignment details
A total of 116 participants rolled over in this study of which 115 participants received gantenerumab in part 1. 59 participants rolled over from OLE WN25203 & 56 participants rolled over from WN28745. Due to negative pre-planned analysis of studies WN39658 & WN29922, this study was terminated by sponsor, & no participant was rolled over to Part 2.
Participants by arm
| Arm | Count |
|---|---|
| SCarlet RoAD Participants enrolled from the open label extension (OLE) part of parent study WN25203, received gantenerumab, up to 1200 milligram (mg), subcutaneous (SC) injection, every 4 weeks (Q4W) for up to 129 weeks. | 59 |
| Marguerite RoAD Participants enrolled from the OLE part of parent study WN28745, received gantenerumab, up to 1200 mg, SC injection, Q4W for up to 129 weeks. | 57 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Progressive Disease | 9 | 6 |
| Overall Study | Reason Not Specified | 2 | 7 |
| Overall Study | Study Terminated by Sponsor | 30 | 33 |
| Overall Study | Withdrawal by Subject | 9 | 10 |
Baseline characteristics
| Characteristic | Marguerite RoAD | Total | SCarlet RoAD |
|---|---|---|---|
| Age, Continuous | 75.2 years STANDARD_DEVIATION 8.3 | 76.6 years STANDARD_DEVIATION 7.7 | 78.0 years STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 13 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 103 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 13 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 42 Participants | 98 Participants | 56 Participants |
| Sex: Female, Male Female | 35 Participants | 71 Participants | 36 Participants |
| Sex: Female, Male Male | 22 Participants | 45 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 59 | 0 / 56 |
| other Total, other adverse events | 43 / 59 | 39 / 56 |
| serious Total, serious adverse events | 11 / 59 | 10 / 56 |
Outcome results
Primary
Number of Participants Who Discontinued Treatment Due to AEs
An AE was defined as any untoward medical occurrence in a participant administered with gantenerumab and which does not necessarily have a causal relationship with gantenerumab. SAE is any significant hazard, contraindication, side effect that is fatal or life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is medically significant or requires intervention to prevent one or other of the outcomes listed above, and which does not necessarily have a causal relationship with gantenerumab.
Time frame: Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)
Population: Safety evaluable population included all the participants who received at least one dose of gantenerumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCarlet RoAD | Number of Participants Who Discontinued Treatment Due to AEs | 3 Participants |
| Marguerite RoAD | Number of Participants Who Discontinued Treatment Due to AEs | 0 Participants |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was defined as any untoward medical occurrence in a participant administered with gantenerumab and which does not necessarily have a causal relationship with gantenerumab. A Serious Adverse Event (SAE) is any significant hazard, contraindication, side effect that is fatal or life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is medically significant or requires intervention to prevent one or other of the outcomes listed above, and which does not necessarily have a causal relationship with gantenerumab.
Time frame: Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)
Population: Safety evaluable population included all the participants who received at least one dose of gantenerumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SCarlet RoAD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 54 Participants |
| SCarlet RoAD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 11 Participants |
| Marguerite RoAD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 49 Participants |
| Marguerite RoAD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 10 Participants |
Primary
Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) AEs
Time frame: Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)
Population: Safety evaluable population included all the participants who received at least one dose of gantenerumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCarlet RoAD | Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) AEs | 0 Participants |
| Marguerite RoAD | Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) AEs | 0 Participants |
Primary
Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) AEs
Time frame: Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)
Population: Safety evaluable population included all the participants who received at least one dose of gantenerumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCarlet RoAD | Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) AEs | 0 Participants |
| Marguerite RoAD | Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) AEs | 0 Participants |
Primary
Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab
Time frame: Up to Week 133
Population: Safety evaluable population included all the participants who received at least one dose of gantenerumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCarlet RoAD | Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab | 3 Participants |
| Marguerite RoAD | Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab | 1 Participants |
Primary
Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, & attempts with actual/potential lethality. Categories have binary responses (yes/no) & include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a yes answer to any of the listed categories. Score of 0= no suicide risk present. Score of 1 or higher= suicidal ideation/behavior. Number of participants with any suicidal ideation/behavior were reported.
Time frame: Baseline (Day 1), up to Week 104
Population: Safety evaluable population included all the participants who received at least one dose of gantenerumab. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SCarlet RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Week 24 | 2 Participants |
| SCarlet RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Week 76 | 0 Participants |
| SCarlet RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Week 52 | 1 Participants |
| SCarlet RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Week 104 | 0 Participants |
| SCarlet RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline | 3 Participants |
| Marguerite RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Week 104 | 0 Participants |
| Marguerite RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline | 0 Participants |
| Marguerite RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Week 24 | 0 Participants |
| Marguerite RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Week 52 | 0 Participants |
| Marguerite RoAD | Number of Participants With Change in Any Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Week 76 | 1 Participants |
Primary
Number of Participants With Injection-Site Reactions
Time frame: Baseline [Day 1] up to 4 weeks after the last dose of study drug (Up to Week 133)
Population: Safety evaluable population included all the participants who received at least one dose of gantenerumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCarlet RoAD | Number of Participants With Injection-Site Reactions | 14 Participants |
| Marguerite RoAD | Number of Participants With Injection-Site Reactions | 7 Participants |