Table 1 Shows a summary of the design and main findings of included studies
Study ID | Study Design | Population | Sample size in each group | Finding | |
|---|---|---|---|---|---|
Bapineuzumab | Placebo | ||||
Salloway et al., 2009 [13] | - Phase II, randomized in a ratio of 8:7, double- blinded. - Patients received 6 infusions of bapineuzumab or placebo, 13 weeks apart. Final assessment occurred at 78 weeks. | • Patients aged from 50 to 85 years. • Met criteria for AD and had MRI findings, consistent with AD. • Mini-Mental State Examination (MMSE) score of 16 to 26. • Rosen Modified Hachinski Ischemic score < 4. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 124 patients were allocated in 1 of 4 sequential dose cohorts (0.15, 0.5, 1.0, or 2.0 mg/kg). | 110 patients were allocated to Placebo group. | No significant treatment differences were found in the primary efficacy analysis. However, exploratory analyses showed potential differences on cognitive and functional outcomes in study completers and APOE- 4 non-carriers. |
Salloway et al., 2014 (Carriers) [16] | - Phase IIIa, randomized in a ratio of 3:2, double blinded. - Patients received 6 infusions of bapineuzumab or placebo, 13 weeks apart. Final assessment occurred at 78 weeks. | • Patients aged from 50 to 88 years. • Met criteria for AD and had MRI findings, consistent with AD. • Carriers of the apolipoprotein E (APOE) ε4 allele • Mini–Mental State Examination (MMSE) of 16 to 26. • Score on the Hachinski Ischemic scale of 4 or lower. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 658 patients were allocated to bapineuzumab 0.5 mg per kg group. | 432 patients were allocated to placebo group. | No differences between bapineuzumab and placebo in terms of change from baseline in the ADAS-cog11 and DAD scores (P = 0.80 and 0.34 respectively). Therefore, Bapineuzumab did not improve the clinical outcomes in AD patients. |
Salloway et al., 2014 (Non-carriers) [16] | - Phase IIIb, randomized 3:3:4, double blinded. - Patients received 6 infusions of bapineuzumab or placebo, 13 weeks apart. Final assessment occurred at 78 weeks. | • Patients aged from 50 to 88 years. • Met criteria for AD and had MRI findings, consistent with AD. • Non-Carriers of the apolipoprotein E (APOE) ε4 allele • Mini–Mental State Examination (MMSE) of 16 to 26. • Score on the Hachinski Ischemic scale of 4 or lower. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 621 patients were allocated to bapineuzumab groups. - Bapineuzumab 0.5 mg per kg: 337 - Bapineuzumab 1.0 mg per kg: 307 | 524 patients were allocated to placebo group. | No differences were found between bapineuzumab (Both doses) and placebo groups in terms of change from baseline in the ADAS-cog11 and DAD scores (P = 0.64 and 0.07 respectively). Therefore, bapineuzumab did not improve the clinical outcomes in patients with AD. |
Black et al., 2010 [15] | - Phase II, randomized, third-party unblinded. - Patients received bapineuzumab or placebo with dose escalation every 10 weeks. Final assessment occurred at 52 weeks. | • Patients aged from 50 to 88 years. • Met criteria for AD and had MRI findings, consistent with AD. • Mini-Mental State Examination (MMSE) score of 14 to 26. • Rosen Modified Hachinski Ischemic score ≤ 4. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 22 patients were allocated to bapineuzumab groups. - Bapineuzumab 0.5 mg/kg: 6 - Bapineuzumab 1.5 mg/kg: 6 - Bapineuzumab 5 mg/kg: 10 | 8 patients were allocated to placebo group. | MMSE scores improved at lower doses of bapineuzumab (0.5 and 1.5 mg/kg) compared to placebo, but not with the highest dose (5 mg/kg). Moreover, The 5 mg/kg dose was significantly associated with MRI amyloid abnormalities that resolved over time. |
Arai et al., 2015 [17] | - Phase I, randomized, double- blinded. - Patients received one infusion of the study drug or placebo. Final assessment occurred at 52 weeks. | • Patients aged from 50 to 85 years. • Met criteria for AD and had MRI findings, consistent with AD. • Mini-Mental State Examination (MMSE) score of 14 to 26. • Rosen Modified Hachinski Ischemic score ≤ 4. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 24 patients were equally allocated to 4 dose cohorts (0.15, 0.5, 1, or 2 mg/kg). | 8 patients were allocated to placebo group. | Plasma β-amyloid levels increased with increasing doses of bapineuzumab. Bapineuzumab was well tolerated at all doses in Japanese patients with mild to moderate AD. |
Rinne et al., 2010 [14] | - Phase II, randomized, double- blinded. - Patients received 6 infusions of bapineuzumab or placebo, 13 weeks apart. Final assessment occurred at 78 weeks. | • Patients aged from 50 to 85 years. • Met criteria for AD and had MRI findings, consistent with AD. • Mini-Mental State Examination (MMSE) score of 18 to 26. • Rosen Modified Hachinski Ischemic score ≤ 4. • Participants had amyloid-B loads in the range expected for patients with Alzheimer’s disease, defined as 11C–PiB PET retention ratios relative to the cerebellum of 1 to 5 or more in at least three brain regions among the anterior cingulate, posterior cingulate, frontal, temporal, and parietal cortices. • Participants were excluded from the study if they had a clinically significant neurological (other than AD) or systemic disease. | 19 patients were allocated to 1 of 3 sequential dose cohorts (0.5, 1.0, 2.0 mg/kg). | 7 patients were allocated to placebo group. | Treatment with bapineuzumab for 78 weeks reduced cortical carbon-11-labelled Pittsburgh compound B (C-PiB) retention, compared to placebo. Adverse events were typically mild to moderate in severity and transient in duration. |