Trial Outcomes & Findings for Trial of Andexanet Alfa in ICrH Patients Receiving an Oral FXa Inhibitor (NCT NCT03661528)

Last Updated: 2024-07-03

Results Overview

Effective hemostasis was defined as a change from baseline in National Institutes of Health Stroke Scale (NIHSS) of + 6 or less at the 12 hour timepoint and ≤35% increase in haematoma volume compared to baseline on a repeat computed tomography (CT) or magnetic resonance imaging (MRI) scan at 12 hours and no rescue therapies administered between 3 hours and 12 hours after randomization (defined as excellent or good hemostasis). The NIHSS is a validated quantitative assessment tool to measure stroke-related neurological deficits and ranges from 0 (no neurological deficits) to a maximum of 42, indicative of a very severe level of impairment. Data presented is for the number of participants who achieved effective hemostasis (excellent or good hemostasis), as adjudicated by the independent Endpoint Adjudication Committee (IEAC).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

530 participants

Primary outcome timeframe

Baseline up to 12 hours

Results posted on

2024-07-03

Participant Flow

Data collected for the Andexanet Alfa arm were prespecified to be collected as a single Arm/Group regardless of the dose level the participant received.

Participant milestones

Participant milestones
Measure	Andexanet Alfa Participants received a regimen of andexanet alfa administered as an intravenous (IV) bolus, immediately followed by a continuous infusion. Dosing regimen was based on which FXa inhibitor the participants received and the amount and timing of the most recent dose of treatment.	Usual Care Participants received usual care. Usual care consisted of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians considered to be appropriate.
Overall Study STARTED	263	267
Overall Study Received at Least 1 Dose of Study Drug	262	265
Overall Study COMPLETED	180	193
Overall Study NOT COMPLETED	83	74

Reasons for withdrawal

Reasons for withdrawal
Measure	Andexanet Alfa Participants received a regimen of andexanet alfa administered as an intravenous (IV) bolus, immediately followed by a continuous infusion. Dosing regimen was based on which FXa inhibitor the participants received and the amount and timing of the most recent dose of treatment.	Usual Care Participants received usual care. Usual care consisted of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians considered to be appropriate.
Overall Study Death	1	0
Overall Study Physician Decision	3	1
Overall Study Other than Specified	5	2
Overall Study Withdrawal by Subject	5	3
Overall Study Disease Progression	8	13
Overall Study Adverse Event	61	55

Baseline Characteristics

Trial of Andexanet Alfa in ICrH Patients Receiving an Oral FXa Inhibitor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Andexanet Alfa n=263 Participants Participants received a regimen of andexanet alfa administered as an intravenous (IV) bolus, immediately followed by a continuous infusion. Dosing regimen was based on which FXa inhibitor the participants received and the amount and timing of the most recent dose of treatment.	Usual Care n=267 Participants Participants received usual care. Usual care consisted of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians considered to be appropriate.	Total n=530 Participants Total of all reporting groups
Age, Continuous	79.4 years STANDARD_DEVIATION 8.51 • n=5 Participants	78.7 years STANDARD_DEVIATION 8.61 • n=7 Participants	79.0 years STANDARD_DEVIATION 8.56 • n=5 Participants
Sex: Female, Male Female	117 Participants n=5 Participants	128 Participants n=7 Participants	245 Participants n=5 Participants
Sex: Female, Male Male	146 Participants n=5 Participants	139 Participants n=7 Participants	285 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	227 Participants n=5 Participants	237 Participants n=7 Participants	464 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	21 Participants n=5 Participants	17 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	239 Participants n=5 Participants	247 Participants n=7 Participants	486 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	16 Participants n=5 Participants	12 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 12 hours

Population: Measured in the ITT set, primary efficacy population, which included all participants randomized to study intervention based on the first data cut-off. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Andexanet Alfa n=224 Participants Participants received a regimen of andexanet alfa administered as an intravenous (IV) bolus, immediately followed by a continuous infusion. Dosing regimen was based on which FXa inhibitor the participants received and the amount and timing of the most recent dose of treatment.	Usual Care n=228 Participants Participants received usual care. Usual care consisted of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians considered to be appropriate.
Number of Participants Who Achieved Effective Hemostasis	150 Participants	121 Participants

SECONDARY outcome

Timeframe: Baseline up to 2 hours

Anti-FXa activity was measured from plasma samples to assess the anticoagulant status of FXa inhibitors using a modified chromogenic assay performed at a Central Laboratory. Nadir was defined as the minimum anti-FXa activity post-randomization.

Outcome measures

Outcome measures
Measure	Andexanet Alfa n=203 Participants Participants received a regimen of andexanet alfa administered as an intravenous (IV) bolus, immediately followed by a continuous infusion. Dosing regimen was based on which FXa inhibitor the participants received and the amount and timing of the most recent dose of treatment.	Usual Care n=199 Participants Participants received usual care. Usual care consisted of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians considered to be appropriate.
Percentage Change From Baseline to Nadir in Anti-FXa Activity	-94.41 Percent change Interval -99.1 to 1805.0	-27.46 Percent change Interval -97.9 to 416.0

Adverse Events

Andexanet Alfa

Serious events: 120 serious events

Other events: 198 other events

Deaths: 75 deaths

Usual Care

Serious events: 96 serious events

Other events: 200 other events

Deaths: 70 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Andexanet Alfa n=262 participants at risk Participants received a regimen of andexanet alfa administered as an intravenous (IV) bolus, immediately followed by a continuous infusion. Dosing regimen was based on which FXa inhibitor the participants received and the amount and timing of the most recent dose of treatment.	Usual Care n=265 participants at risk Participants received usual care. Usual care consisted of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians considered to be appropriate.
Infections and infestations Pneumonia	10.7% 28/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	9.4% 25/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Infections and infestations Pneumonia aspiration	7.3% 19/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	6.0% 16/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Infections and infestations Urinary tract infection	20.6% 54/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	16.6% 44/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Metabolism and nutrition disorders Hypokalaemia	15.3% 40/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	10.6% 28/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Psychiatric disorders Delirium	7.6% 20/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	9.8% 26/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Psychiatric disorders Insomnia	5.3% 14/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	3.4% 9/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Nervous system disorders Headache	9.2% 24/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	7.2% 19/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Vascular disorders Hypertension	6.9% 18/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	7.2% 19/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Gastrointestinal disorders Constipation	14.9% 39/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	9.4% 25/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Gastrointestinal disorders Nausea	8.8% 23/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	6.4% 17/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
Gastrointestinal disorders Vomiting	3.4% 9/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	5.3% 14/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.
General disorders Pyrexia	8.8% 23/262 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.	8.3% 22/265 • Up to approximately 30 days All-cause mortality (ACM) is presented for all enrolled participants. Serious adverse events and other adverse event (AE) data are presented for all randomized participants who received study treatment and were analyzed according to the actual treatment received. ACM data includes participants who died due to AEs, an initial intracranial hemorrhage (disease progression), or participants who were discontinued from the study for other reasons and died on, or after, the day of discontinuation.

Additional Information

Alexion Pharmaceuticals, Inc.

Phone: +1.855.752.2356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place