Table 3. Summary of Adverse Events During the CREAD and CREAD2 Studies.
| Event | No. (%) | |||
|---|---|---|---|---|
| CREAD | CREAD2 | |||
| Placebo (n = 405) | Crenezumab (n = 404) | Placebo (n = 398) | Crenezumab (n = 404) | |
| Participants with any adverse event | 337 (83.2) | 347 (85.9) | 291 (73.1) | 297 (73.5) |
| Participants with any serious adverse event | 63 (15.6) | 67 (16.6) | 42 (10.6) | 33 (8.2) |
| Adverse event of severe intensity | 49 (12.1) | 52 (12.9) | 24 (6.0) | 20 (5.0) |
| Participants with at least one adverse event resulting in treatment discontinuation | 15 (3.7) | 14 (3.5) | 9 (2.3) | 5 (1.2) |
| Death | 5 (1.2) | 8 (2.0) | 6 (1.5) | 0 |
| Adverse events, by PT, with incidence of ≥5% in either groupa | ||||
| Headache | 45 (11.1) | 39 (9.7) | 22 (5.5) | 25 (6.2) |
| Nasopharyngitis | 33 (8.1) | 40 (9.9) | 25 (6.3) | 24 (5.9) |
| Fall | 33 (8.1) | 43 (10.6) | 24 (6.0) | 20 (5.0) |
| Hypertension | 22 (5.4) | 27 (6.7) | 15 (3.8) | 27 (6.7) |
| Back pain | 31 (7.7) | 26 (6.4) | 15 (3.8) | 16 (4.0) |
| Upper respiratory tract infection | 29 (7.2) | 33 (8.2) | 13 (3.3) | 10 (2.5) |
| Anxiety | 21 (5.2) | 28 (6.9) | 17 (4.3) | 18 (4.5) |
| Depression | 27 (6.7) | 28 (6.9) | 14 (3.5) | 15 (3.7) |
| Diarrhea | 26 (6.4) | 25 (6.2) | 15 (3.8) | 17 (4.2) |
| Dizziness | 27 (6.7) | 23 (5.7) | 10 (2.5) | 19 (4.7) |
| Serious adverse events, by PT, with incidence of ≥0.5% in either group | ||||
| Fall | 1 (0.2) | 4 (1.0) | 6 (1.5) | 2 (0.5) |
| Pneumonia | 3 (0.7) | 5 (1.2) | 2 (0.5) | 1 (0.2) |
| Subdural hematoma | 3 (0.7) | 4 (1.0) | 0 | 3 (0.7) |
| Syncope | 4 (1.0) | 3 (0.7) | 2 (0.5) | 0 |
| Dehydration | 0 | 3 (0.7) | 0 | 1 (0.2) |
| Adverse events of interest | ||||
| New findings of amyloid-related imaging abnormalitiesb | ||||
| With edemac | 1/397 (0.3) | 1/399 (0.3) | 0 | 1/398 (0.3) |
| With hemorrhage | 31/397 (7.8) | 39/399 (9.8) | 23/388 (5.9) | 20/398 (5.0) |
| Infusion-related reactionsd | 41 (10.1) | 47 (11.6) | 31 (7.8) | 24 (5.9) |
| Pneumoniae | 7 (1.7) | 10 (2.5) | 8 (2.0) | 3 (0.7) |
Abbreviations: CREAD, A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study of Crenezumab in Patients With Prodromal to Mild Alzheimer’s Disease; PT, preferred term.
Adverse events by PT according to Medical Dictionary for Regulatory Activities version 22.0.
Percentages are based on participants with postbaseline safety magnetic resonance imaging data.
Of 3 reported amyloid-related imaging abnormality–edema events, 2 were asymptomatic and 1 participant experienced worsening of a preexisting headache at the time of amyloid-related imaging abnormality–edema detection (crenezumab arm in the CREAD study). All were mild (Barkhof grand total score between 1 and 3).
Infusion-related reaction rates were similar between both groups (CREAD: placebo, 41 [10.1%], crenezumab, 47 [11.6%]; CREAD2: placebo, 31 [7.8%]; crenezumab, 24 [5.9%]) with the most common reactions being headache, phlebitis, and back pain. Most infusion-related reactions were nonserious and were mild to moderate in severity.
Of the 17 reported cases of pneumonia, an adverse event of interest, 5 cases were suspected to be treatment related (CREAD: placebo, 2 [0.5%], crenezumab, 2 [0.5%]; CREAD2: placebo, 1 [0.3%], crenezumab 0).