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An Open-Label, Multicenter, Rollover Study to Evaluate the Safety, Tolerability, and Efficacy of Long-Term Gantenerumab Administration in Participants With Alzheimer's Disease

A Study to Evaluate the Safety, Tolerability, and Efficacy of Long-term Gantenerumab Administration in Participants With Alzheimer's Disease (AD)

1381

Participants who completed the WN29922 (NCT03444870) or WN39658 (NCT03443973) study. These studies included patients aged 50-90 years with prodromal or mild Alzheimer's disease, and evidence of amyloid beta pathology. The mean age of all 1381 participants at the start of WN42171 (NCT04374253) study was 73.4 years, with 587 males (42.5%) and 794 females (57.5%).

Of the participants who were in WN29922 or WN39658 study, this study included 647 participants who had previously received gantenerumab and rolled over from the double-blind treatment (DBT) part, 691 participants who had previously received placebo and rolled over from the DBT part and 43 participants who rolled over from the open label extension (OLE) part. The participants rolling over from the gantenerumab group in the DBT part and from the OLE part continued to receive gantenerumab 510 mg every 2 weeks (Q2W). The participants rolling over from the placebo group in the DBT part received at least 3 doses of gantenerumab 120 mg Q4W, at least 3 doses of 255 mg Q4W, and at least 3 doses of 510 mg Q4W, followed by gantenerumab 510 mg Q2W. Since this study was terminated by Sponsor following the negative results of WN29922 and WN39658 studies, the mean treatment duration was approximately 10 months.

The study showed that gantenerumab was well tolerated. Out of 676 participants who had previously received gantenerumab and 705 participants who had previously received placebo in WN29922 or WN39658 study (the same hereinafter), 512 (75.7%) and 523 (74.2%) participants experienced at least one adverse event (AE), and 58 (8.6%) and 74 (10.5%) participants experienced at least one serious AE (SAE). Overall, 121 (17.9 %) and 153 (21.7 %) participants had at least one treatment-related AE, and 1 (less than 1 %) and 6 (less than 1 %) participants had at least one treatment-related SAE. Most treatment-related AEs were mild or moderate. The most common treatment-related AEs were injection site reaction (74 [10.9 %] and 58 [8.2 %] participants) and amyloid-related imaging abnormalities - edema/effusion (ARIA-E) (15 [2.2 %] and 69 [9.8 %] participants). A total of 15 (2.2%) and 28 (4.0 %) participants stopped taking study drug because of the treatment-related AEs. Participants most commonly had to stop treatment because of ARIA-H. Five participants in each group died: none of the deaths that occurred were considered to be caused by treatment with the study drug.

Primary outcome measures: Refer to Adverse events. Secondary outcome measures: The secondary objective for this study was to evaluate the efficacy of long-term gantenerumab administered on the basis of the following endpoints. - Clinical Dementia Rating -Sum of Boxes (CDR-SOB) and Global Score (CDR-GS) - Mini-Mental State Examination (MMSE) - Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) and Subscale 13 (ADAS-Cog13) - Verbal Fluency Task - Coding (Digit Symbol Substitution Test) - Functional Activities Questionnaire - Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Total Score and Instrumental Score The results of CDR-SOB for participants who were rolled over from the DBT part of WN29922 or WN39658 study are showed below. The mean change from baseline to Week 52 was 1.50 (standard deviation [SD]: 2.1; n =327) and 1.60 (SD: 1.9; n=336), and the mean change from baseline to Week 104 was 1.80 (SD: 1.9; n=20) and 3.26 (SD: 2.8; n=19) for participants who were in the gantenerumab group or the placebo group in the DBT part of WN29922 or WN39658 study, respectively.

Following the negative results of WN29922 and WN39658 studies, this study was terminated by Sponsor. The study showed that gantenerumab was well tolerated.

No

Qualified researchers may request access to individual patient level data through the clinical study data request platform. For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).

https://jrct.niph.go.jp/latest-detail/jRCT2031200328

Geoffrey A Kerchner, M.D., Ph.D.

F. Hoffmann-La Roche Ltd

1-1 Nihonbashi-Muromachi 2-Chome, Chuo-ku Tokyo

clinical-trials@chugai-pharm.co.jp

Clinical trials information

Chugai Pharmaceutical Co., Ltd.

1-1 Nihonbashi-Muromachi 2-Chome, Chuo-ku Tokyo

+81-120-189-706

clinical-trials@chugai-pharm.co.jp

Complete

Feb. 04, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- Completed Study WN29922 or WN39658, either its double-blind part or OLE part, and did not discontinue study drug early
- The participant should be capable of completing assessments either alone or with the help of the caregiver
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception methods with a failure rate of <1% per year (bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices) during the treatment period and for at least 16 weeks after the final dose of gantenerumab

- Pregnant or breastfeeding, or intending to become pregnant during the study or within at least 16 weeks after the final dose of study drug
- Prematurely discontinued from Study WN29922 or WN39658
- Any medical condition that may jeopardize the participant's safety if he or she continues to receive study treatment
- Received any investigational treatment other than gantenerumab during or since completion of Study WN29922 or WN39658, either its double-blind or OLE part
- Evidence of disseminated leptomeningeal hemosiderosis
- Evidence of intracerebral macrohemorrhage
- Use of prohibited medication
- Evidence of ARIA-E on the last MRI scan report in Study WN29922 or WN39658, either its double-blind or OLE part

Both

Alzheimer's disease

Group 1: participants who were in the active arm in the double blind part in the parent study (WN29922 or WN39658), will continue to receive open-label gantenerumab 510 mg sub-cutaneously (SC) every 2 weeks (Q2W). Participants who are naive to gantenerumab treatment will be required to undergo the 3 step uptitration scheme before receiving target dose of open label gantenerumab, 510 mg sub-cutaneously (SC) every 2 weeks (Q2W).
Group 2: participants who have completed OLE part in the parent study (WN29922 or WN39658), will continue to receive open-label gantenerumab 510 mg sub-cutaneously (SC) every 2 weeks (Q2W)

Safety
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Baseline (OLE Day 1) to Week 104 ]
- Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: From Baseline (OLE Day 1) to Week 104 ]
- Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) [ Time Frame: From Baseline (OLE Day 1) to Week 104 ]
- Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by MRI [ Time Frame: From Baseline (OLE Day 1) to Week 104 ]
- Percentage of Participants with Injection-Site Reactions (ISRs) [ Time Frame: From Baseline (OLE Day 1) to Week 104 ]

Efficacy, Phamacokinetics, Other
- Change in Clinical Dementia Rating (CDR) [ From Baseline (OLE Day 1) to Week 104 ]
- Change in Mini-Mental State Examination (MMSE) [ From Baseline (OLE Day 1) to Week 104 ]
- Change in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) [ From Baseline (OLE Day 1) to Week 104 ]
- Change in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADASCog13) [ From Baseline (OLE Day 1) to Week 104 ]
- Change in Verbal Fluency Task Score [ From Baseline (OLE Day 1) to Week 104 ]
- Change in Coding [ From Baseline (OLE Day 1) to Week 104 ]
- Change in Functional Activities Questionnaire (FAQ) [ From Baseline (OLE Day 1) to Week 104 ]
- Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) [ From Baseline (OLE Day 1) to Week 104 ]
- Plasma Concentration of Gantenerumab Administered SC [ From Baseline (OLE Day 1) to Week 104 ]
- Percentage of Participants with Anti-drug Antibody (ADA) to Gantenerumab [ From Baseline (OLE Day 1) to Week 104 ]

+81-3-6779-8166

Oct. 08, 2020

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