Trial Outcomes & Findings for Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger (NCT NCT04743804)

Last Updated: 2024-10-01

Results Overview

TMA response required the following: 1) Normalization of platelet count without transfusion support during the prior 7 days. 2) Normalization of LDH. 3) Improvement in glomerular filtration rate (eGFR) of \>= 30% compared to baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, and any measurement in between.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

16 participants

Primary outcome timeframe

Week 26

Results posted on

2024-10-01

Participant Flow

Participant milestones

Participant milestones
Measure	Ravulizumab Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.
Overall Study STARTED	9	7
Overall Study Received at Least 1 Dose of Study Drug	9	7
Overall Study COMPLETED	4	1
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Ravulizumab Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.
Overall Study Other	1	0
Overall Study Withdrawal by Subject	0	1
Overall Study Study Terminated by Sponsor	1	4
Overall Study Physician Decision	0	1
Overall Study Death	3	0

Baseline Characteristics

Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ravulizumab n=9 Participants Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo n=7 Participants Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Total n=16 Participants Total of all reporting groups
Age, Continuous	48.2 years STANDARD_DEVIATION 15.75 • n=5 Participants	57.7 years STANDARD_DEVIATION 17.70 • n=7 Participants	52.4 years STANDARD_DEVIATION 16.77 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 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	6 Participants n=5 Participants	3 Participants n=7 Participants	9 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	5 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	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 26

Population: The Modified Intent-to-Treat Analysis Set included all randomized participants, excluding participants who enrolled prior to availability of ST-HUS and ADAMTS13 central laboratory results and were subsequently found to be ineligible after randomization.

Outcome measures

Outcome measures
Measure	Ravulizumab n=9 Participants Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo n=7 Participants Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.
Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline through Week 26

The Kaplan-Meier estimate of time to event of complete TMA response is reported. TMA response required the following: 1) Normalization of platelet count without transfusion support during the prior 7 days. 2) Normalization of LDH. 3) Improvement in eGFR of \>= 30% compared to baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, and any measurement in between. Participants who did not have a response were censored at the date of last visit or study discontinuation at the time when the analysis was performed.

Outcome measures

Outcome measures
Measure	Ravulizumab n=2 Participants Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo n=3 Participants Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.
Time to Complete TMA Response	NA days Interval 21.0 to Too few participants experienced the event to estimate the time to event median and upper limit of 95% CI.	NA days Interval 16.0 to Too few participants experienced the event to estimate the time to event median and upper limit of 95% CI.

SECONDARY outcome

Timeframe: Week 26

Hematologic response required the following: (1) Normalization of platelet count without transfusion support during the prior 7 days, and (2) normalization of LDH.

Outcome measures

Outcome measures
Measure	Ravulizumab n=9 Participants Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo n=7 Participants Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.
Number of Participants With Hematologic Response at Week 26	5 Participants	6 Participants

SECONDARY outcome

Timeframe: Week 26

Renal response is improvement in eGFR of \>= 30% compared to baseline. If a participant is on dialysis ≤5 days prior to the date of eGFR assessment, the eGFR will be set to 10 milliliter/minute/1.73 meter square (mL/min/1.73 m\^2) for that assessment. If a participant is on dialysis during the entire 26 week randomized Treatment Period, or through early discontinuation of study drug, then the change in eGFR was not calculated.

Outcome measures

Outcome measures
Measure	Ravulizumab n=9 Participants Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo n=7 Participants Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.
Number of Participants With Renal Response at Week 26	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Week 26

Outcome measures

Outcome measures
Measure	Ravulizumab n=5 Participants Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo n=4 Participants Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.
Number of Participants On Dialysis at Week 26	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26

If a participant is on dialysis during the entire 26 week randomized Treatment Period, or through early discontinuation of study drug, then the change in eGFR was not calculated.

Outcome measures

Outcome measures
Measure	Ravulizumab n=5 Participants Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo n=4 Participants Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.
Change From Baseline in eGFR at Week 26	25.8 milliliter/minute/1.73 meter^2 Standard Deviation 19.90	17.5 milliliter/minute/1.73 meter^2 Standard Deviation 7.59

Adverse Events

Ravulizumab

Serious events: 6 serious events

Other events: 9 other events

Deaths: 3 deaths

Placebo

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Alexion Pharmaceuticals, Inc.

Phone: 855-752-2356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ravulizumab n=9 participants at risk Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.	Placebo n=7 participants at risk Participants received weight-based dosages of placebo matched to ravulizumab for 26 weeks during the Initial Treatment Period. Participants received a loading dose of placebo matched to ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter.
Infections and infestations COVID-19 pneumonia	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Infections and infestations Epstein-Barr viraemia	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Infections and infestations Pneumonia	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Infections and infestations Urinary tract infection	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Infections and infestations Escherichia urinary tract infection	0.00% 0/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	14.3% 1/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Infections and infestations Sepsis	0.00% 0/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	14.3% 1/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Nervous system disorders Ischaemic stroke	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Nervous system disorders Seizure	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Renal and urinary disorders Renal failure	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Renal and urinary disorders Renal pseudoaneurysm	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Blood and lymphatic system disorders Thrombotic microangiopathy	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Injury, poisoning and procedural complications Shunt thrombosis	11.1% 1/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	0.00% 0/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	14.3% 1/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.00% 0/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	14.3% 1/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.
Skin and subcutaneous tissue disorders Toxic epidermal necrolysis	0.00% 0/9 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.	14.3% 1/7 • Baseline up to Week 34 The Safety Analysis Set included all participants who received at least 1 dose of study intervention.