Alzheimer's Disease
Conditions
Brief summary
The purpose of this study is to assess the long-term safety and tolerability of ABBV-8E12 in participants with early AD.
Interventions
DRUGTilavonemab
solution for IV infusion
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
57 Years to 88 Years
Healthy volunteers
No
Inclusion criteria
* All subjects with early AD who complete Study M15-566 (NCT02880956), meet all inclusion criteria, and do not meet any
Exclusion criteria
are eligible for enrollment * Subject was compliant during participation in Study M15-566 (NCT02880956) * Subject has an identified, reliable study partner who has frequent contact with the subject and who will provide information as to the subject's cognitive and functional abilities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | From first dose of study drug to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. | Treatment emergent adverse events (TEAEs) are defined as any adverse event (AE) from the time of study drug administration until 20 weeks after discontinuation of study drug. An AE is defined as any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any event that: results in death; is life-threatening; results in hospitalization or prolongation of hospitalization; is a congenital anomaly; results in persistent or significant disability/incapacity; is an important medical event requiring medical or surgical intervention to prevent serious outcome. Severity of AEs was categorized as mild, moderate, or severe. Relationship of the AE to the study treatment was categorized as having a reasonable possibility or no reasonable possibility. |
| Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. | Clinical laboratory PCS criteria were adapted from National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. |
| Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. | Clinical laboratory PCS criteria were adapted from NCI CTCAE version 4.03 |
| Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. | The C-SSRS is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide. |
| Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days. | — |
Countries
Australia, Belgium, Canada, Denmark, Finland, Italy, New Zealand, Spain, Sweden, United States
Participant flow
Recruitment details
A total of 364 participants who had completed the parent study (Study M15-566; NCT02880956) were enrolled into this extension study from a total of 57 sites in the United States, Australia, Belgium, Canada, Denmark, Finland, Italy, New Zealand, Spain, and Sweden.
Pre-assignment details
Prior to enrollment, 87 participants had received tilavonemab 300 mg, 97 participants had received tilavonemab 1000 mg, 88 participants had received tilavonemab 2000 mg, and 92 participants had received placebo in the parent study. One enrolled participant did not receive any study drug and was not included in any analysis.
Participants by arm
| Arm | Count |
|---|---|
| 300 mg/1000 mg Tilavonemab Participants who received 300 mg tilavonemab in Study M15-566 received 1000 mg tilavonemab in Study M15-570 via IV infusion every 4 weeks. | 87 |
| 1000 mg/1000 mg Tilavonemab Participants who received 1000 mg tilavonemab in Study M15-566 were continued on the same dose in Study M15-570 via IV infusion every 4 weeks. | 97 |
| 2000 mg/2000 mg Tilavonemab Participants who received 2000 mg tilavonemab in Study M15-566 were continued on the same dose in Study M15-570 via IV infusion every 4 weeks. | 88 |
| PBO/2000 mg Tilavonemab Participants who received PBO in Study M15-566 received 2000 mg tilavonemab in Study M15-570 via IV infusion every 4 weeks. | 91 |
| Total | 363 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 0 | 4 |
| Overall Study | COVID-19 Infection | 0 | 1 | 0 | 0 |
| Overall Study | COVID-19 Logistical Restrictions | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 2 | 1 |
| Overall Study | Other, Not Specified | 79 | 77 | 74 | 78 |
| Overall Study | Withdrawal by Subject | 4 | 14 | 12 | 8 |
Baseline characteristics
| Characteristic | 300 mg/1000 mg Tilavonemab | 1000 mg/1000 mg Tilavonemab | 2000 mg/2000 mg Tilavonemab | PBO/2000 mg Tilavonemab | Total |
|---|---|---|---|---|---|
| Age, Customized < 65 years | 8 Participants | 11 Participants | 14 Participants | 10 Participants | 43 Participants |
| Age, Customized >= 65 years | 79 Participants | 86 Participants | 74 Participants | 81 Participants | 320 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants | 4 Participants | 3 Participants | 4 Participants | 16 Participants |
| Race/Ethnicity, Customized None | 82 Participants | 93 Participants | 85 Participants | 87 Participants | 347 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 81 Participants | 94 Participants | 86 Participants | 89 Participants | 350 Participants |
| Sex: Female, Male Female | 39 Participants | 48 Participants | 48 Participants | 56 Participants | 191 Participants |
| Sex: Female, Male Male | 48 Participants | 49 Participants | 40 Participants | 35 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 87 | 1 / 97 | 1 / 88 | 0 / 91 |
| other Total, other adverse events | 26 / 87 | 37 / 97 | 33 / 88 | 26 / 91 |
| serious Total, serious adverse events | 16 / 87 | 11 / 97 | 12 / 88 | 10 / 91 |
Outcome results
Primary
Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease
Time frame: Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days.
Population: Safety Data Set: All participants who received at least 1 dose of study drug in Study M15-570. Participants with postbaseline value for the respective parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 300 mg/1000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Questionable Cerebral Edemas | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | New Microhemorrhage(s) | 4 Participants |
| 300 mg/1000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Cerebral Edemas | 1 Participants |
| 300 mg/1000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Severe White Matter Disease | 9 Participants |
| 1000 mg/1000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Cerebral Edemas | 1 Participants |
| 1000 mg/1000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Questionable Cerebral Edemas | 1 Participants |
| 1000 mg/1000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Severe White Matter Disease | 5 Participants |
| 1000 mg/1000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | New Microhemorrhage(s) | 5 Participants |
| 2000 mg/2000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Cerebral Edemas | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Severe White Matter Disease | 6 Participants |
| 2000 mg/2000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | New Microhemorrhage(s) | 11 Participants |
| 2000 mg/2000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Questionable Cerebral Edemas | 0 Participants |
| PBO/2000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | New Microhemorrhage(s) | 5 Participants |
| PBO/2000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Questionable Cerebral Edemas | 0 Participants |
| PBO/2000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Severe White Matter Disease | 5 Participants |
| PBO/2000 mg Tilavonemab | Brain Magnetic Resonance Imaging (MRI) Results: Number of Participants With Cerebral Edemas, New Microhemorrhage(s), and Severe White Matter Disease | Cerebral Edemas | 0 Participants |
Primary
Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values
Clinical laboratory PCS criteria were adapted from NCI CTCAE version 4.03
Time frame: Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days.
Population: Safety Data Set: All participants who received at least 1 dose of study drug in Study M15-570.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Creatinine (> 1.5 × ULN) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Triglycerides (> 5.7 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Glucose - Low (< 2.2 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Potassium - High (> 6 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Calcium - Low (< 1.75 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Aspartate Aminotransferase (> 3 × ULN) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Calcium - High (> 3.1 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Alanine Aminotransferase (> 3 × ULN) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Cholesterol (> 12.92 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Potassium - Low (< 3 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Alkaline Phosphatase (> 2.5 × ULN) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Uric acid (> 590 μmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Sodium - High (> 155 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Sodium - Low (< 130 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Bilirubin (> 1.5 × ULN) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Phosphate (< 0.6 mmol/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Albumin (< 20 g/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Glucose - High (> 13.9 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Triglycerides (> 5.7 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Alanine Aminotransferase (> 3 × ULN) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Aspartate Aminotransferase (> 3 × ULN) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Alkaline Phosphatase (> 2.5 × ULN) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Bilirubin (> 1.5 × ULN) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Creatinine (> 1.5 × ULN) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Calcium - Low (< 1.75 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Calcium - High (> 3.1 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Potassium - High (> 6 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Glucose - Low (< 2.2 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Glucose - High (> 13.9 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Albumin (< 20 g/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Sodium - Low (< 130 mmol/L) | 1 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Sodium - High (> 155 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Potassium - Low (< 3 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Cholesterol (> 12.92 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Phosphate (< 0.6 mmol/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Uric acid (> 590 μmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Glucose - Low (< 2.2 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Glucose - High (> 13.9 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Bilirubin (> 1.5 × ULN) | 1 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Alanine Aminotransferase (> 3 × ULN) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Uric acid (> 590 μmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Sodium - Low (< 130 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Alkaline Phosphatase (> 2.5 × ULN) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Phosphate (< 0.6 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Sodium - High (> 155 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Albumin (< 20 g/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Aspartate Aminotransferase (> 3 × ULN) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Potassium - Low (< 3 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Cholesterol (> 12.92 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Calcium - Low (< 1.75 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Potassium - High (> 6 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Calcium - High (> 3.1 mmol/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Creatinine (> 1.5 × ULN) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Triglycerides (> 5.7 mmol/L) | 1 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Phosphate (< 0.6 mmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Glucose - Low (< 2.2 mmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Bilirubin (> 1.5 × ULN) | 1 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Triglycerides (> 5.7 mmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Alanine Aminotransferase (> 3 × ULN) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Glucose - High (> 13.9 mmol/L) | 1 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Albumin (< 20 g/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Potassium - Low (< 3 mmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Calcium - High (> 3.1 mmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Alkaline Phosphatase (> 2.5 × ULN) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Creatinine (> 1.5 × ULN) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Uric acid (> 590 μmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Sodium - Low (< 130 mmol/L) | 1 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Cholesterol (> 12.92 mmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Calcium - Low (< 1.75 mmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Potassium - High (> 6 mmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Sodium - High (> 155 mmol/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Clinical Chemistry: Percentage of Participants With Postbaseline PCS Values | Aspartate Aminotransferase (> 3 × ULN) | 0 Participants |
Primary
Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period
The C-SSRS is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide.
Time frame: Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days.
Population: Safety Data Set: All participants who received at least 1 dose of study drug in Study M15-570.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 300 mg/1000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal behaviors or ideations | 4 Participants |
| 300 mg/1000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal behaviors | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal ideations | 4 Participants |
| 300 mg/1000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal ideations only (No Suicidal Behavior) | 4 Participants |
| 1000 mg/1000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal behaviors | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal ideations | 3 Participants |
| 1000 mg/1000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal ideations only (No Suicidal Behavior) | 3 Participants |
| 1000 mg/1000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal behaviors or ideations | 3 Participants |
| 2000 mg/2000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal ideations | 8 Participants |
| 2000 mg/2000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal behaviors | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal ideations only (No Suicidal Behavior) | 8 Participants |
| 2000 mg/2000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal behaviors or ideations | 8 Participants |
| PBO/2000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal ideations only (No Suicidal Behavior) | 4 Participants |
| PBO/2000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal behaviors | 0 Participants |
| PBO/2000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal behaviors or ideations | 4 Participants |
| PBO/2000 mg Tilavonemab | Columbia-Suicide Severity Rating Scale (C-SSRS) During Double-Blind Treatment Period | Suicidal ideations | 4 Participants |
Primary
Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values
Clinical laboratory PCS criteria were adapted from National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time frame: Baseline to 20 weeks after last dose of study drug; overall median time on treatment was 279 days.
Population: Safety Data Set: All participants who received at least 1 dose of study drug in Study M15-570.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Leukocytes - Low (< 2 × 10^9/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Leukocytes - High (> 100 × 10^9/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Neutrophils - Low (< 1 × 10^9/L) | 1 Participants |
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Lymphocytes - Low (< 0.5 × 10^9/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Lymphocytes - High (> 20 × 10^9/L) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Activated Partial Thromboplastin Time (> ULN) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Prothrombin International Normalized Ratio (> ULN) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Hemoglobin - Low (< 100 g/L) | 1 Participants |
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Hemoglobin - High (> 40 g/L above Upper Limit of Normal [ULN]) | 0 Participants |
| 300 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Platelets - Low (< 75 × 10^9/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Neutrophils - Low (< 1 × 10^9/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Lymphocytes - Low (< 0.5 × 10^9/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Lymphocytes - High (> 20 × 10^9/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Activated Partial Thromboplastin Time (> ULN) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Platelets - Low (< 75 × 10^9/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Prothrombin International Normalized Ratio (> ULN) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Hemoglobin - Low (< 100 g/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Leukocytes - Low (< 2 × 10^9/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Leukocytes - High (> 100 × 10^9/L) | 0 Participants |
| 1000 mg/1000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Hemoglobin - High (> 40 g/L above Upper Limit of Normal [ULN]) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Hemoglobin - Low (< 100 g/L) | 2 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Neutrophils - Low (< 1 × 10^9/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Hemoglobin - High (> 40 g/L above Upper Limit of Normal [ULN]) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Prothrombin International Normalized Ratio (> ULN) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Lymphocytes - Low (< 0.5 × 10^9/L) | 1 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Activated Partial Thromboplastin Time (> ULN) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Platelets - Low (< 75 × 10^9/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Leukocytes - Low (< 2 × 10^9/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Lymphocytes - High (> 20 × 10^9/L) | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Leukocytes - High (> 100 × 10^9/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Lymphocytes - High (> 20 × 10^9/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Leukocytes - Low (< 2 × 10^9/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Activated Partial Thromboplastin Time (> ULN) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Platelets - Low (< 75 × 10^9/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Prothrombin International Normalized Ratio (> ULN) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Neutrophils - Low (< 1 × 10^9/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Leukocytes - High (> 100 × 10^9/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Lymphocytes - Low (< 0.5 × 10^9/L) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Hemoglobin - High (> 40 g/L above Upper Limit of Normal [ULN]) | 0 Participants |
| PBO/2000 mg Tilavonemab | Hematology: Number of Participants With Postbaseline Potentially Clinically Significant (PCS) Values | Hemoglobin - Low (< 100 g/L) | 1 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs
Treatment emergent adverse events (TEAEs) are defined as any adverse event (AE) from the time of study drug administration until 20 weeks after discontinuation of study drug. An AE is defined as any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any event that: results in death; is life-threatening; results in hospitalization or prolongation of hospitalization; is a congenital anomaly; results in persistent or significant disability/incapacity; is an important medical event requiring medical or surgical intervention to prevent serious outcome. Severity of AEs was categorized as mild, moderate, or severe. Relationship of the AE to the study treatment was categorized as having a reasonable possibility or no reasonable possibility.
Time frame: From first dose of study drug to 20 weeks after last dose of study drug; overall median time on treatment was 279 days.
Population: Safety Data Set: All participants who received at least 1 dose of study drug in Study M15-570.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 300 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Fatal TEAE | 1 Participants |
| 300 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Any TEAE | 54 Participants |
| 300 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Severe TEAE | 9 Participants |
| 300 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | TEAE With a Reasonable Possibility of Relationship to Study Drug | 7 Participants |
| 300 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Serious TEAE | 16 Participants |
| 300 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | TEAE Leading to Discontinuation of Study Drug | 2 Participants |
| 1000 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | TEAE Leading to Discontinuation of Study Drug | 4 Participants |
| 1000 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | TEAE With a Reasonable Possibility of Relationship to Study Drug | 10 Participants |
| 1000 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Severe TEAE | 8 Participants |
| 1000 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Serious TEAE | 11 Participants |
| 1000 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Any TEAE | 66 Participants |
| 1000 mg/1000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Fatal TEAE | 1 Participants |
| 2000 mg/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Any TEAE | 59 Participants |
| 2000 mg/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | TEAE Leading to Discontinuation of Study Drug | 0 Participants |
| 2000 mg/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Severe TEAE | 10 Participants |
| 2000 mg/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | TEAE With a Reasonable Possibility of Relationship to Study Drug | 15 Participants |
| 2000 mg/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Serious TEAE | 12 Participants |
| 2000 mg/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Fatal TEAE | 1 Participants |
| PBO/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Serious TEAE | 10 Participants |
| PBO/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Any TEAE | 57 Participants |
| PBO/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Severe TEAE | 7 Participants |
| PBO/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | Fatal TEAE | 0 Participants |
| PBO/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | TEAE Leading to Discontinuation of Study Drug | 5 Participants |
| PBO/2000 mg Tilavonemab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Drug, and Fatal TEAEs | TEAE With a Reasonable Possibility of Relationship to Study Drug | 5 Participants |