Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies

A Phase 2, Uncontrolled, Three-Stage, Dose-Escalation Cohort Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Clinical Activity of OMS721 in Adults With Thrombotic Microangiopathies

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02222545

Enrollment

Registered

2014-08-21

Start date

2014-11-02

Completion date

2020-08-11

Last updated

2024-08-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Thrombotic Microangiopathies

Keywords

TMA, aHUS, HSCT-associated TMA, TTP

Brief summary

The purpose of this study is to assess the safety, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of OMS721 in patients with thrombotic microangiopathies (TMA).

Detailed description

This is a Phase 2, uncontrolled, 3-stage, ascending-dose-escalation study in patients with 1 of 3 forms of TMA: atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenia (TTP), and hematopoietic stem cell transplant - associated TMA (HSCT-associated TMA). In Stage 1 of the study, OMS721 was administered to 3 cohorts, with dose escalation by cohort to identify the optimal dosing regimen. In Stage 2, the dose selected in the first stage was administered to expanded cohorts of patients with distinct etiologies (aHUS alone in 1 cohort and TTP or HSCT-TMA in the other cohort). Patients completing Stage 2 were eligible for continued treatment in Stage 3 if they tolerated OMS721 treatment and derived clinical benefit. Enrollment in the study has been completed.

Interventions

BIOLOGICALOMS721

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Are at least age 18 at screening (Visit 1) 2. Have a diagnosis of primary aHUS, persistent HSCT-associated TMA or TTP 3. No clinically apparent alternative explanation for thrombocytopenia and anemia

Exclusion criteria

1. Had eculizumab therapy within three months prior to screening 2. Have STEC-HUS 3. Have a positive direct Coombs test 4. Have an active systemic bacterial or fungal infection requiring antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed)

Design outcomes

Primary

Measure	Time frame	Description
Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA	Day 1 to 37 days after end of treatment, approximately up to 31 weeks.	Incidence of treatment-emergent adverse events (AEs): clinically significant changes in vital signs, ECG, and laboratory tests were reported as AEs.
Number of Participants With HSCT-TMA Who Respond to OMS721	Day 1 to up to 2 years following the first dose of OMS721	Response defined as: Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status

Secondary

Measure	Time frame	Description
Participants With HSCT-TMA Treated With OMS721: Duration of Response	Study Day 1 to up to 2 years following first dose of OMS721	Number of days from the first response date to the first relapse date
Participants With HSCT-TMA Treated With OMS721: Freedom From Platelet Transfusion	Study Day -14 to 4 weeks following the last platelet transfusion	Number of participants with absence of platelet transfusions
Participants With HSCT-TMA Treated With OMS721: Freedom From Red Blood Cell (RBC) Transfusion	Study Day -14 to 4 weeks following the last RBC transfusion	Number of participants with absence of RBC transfusions
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Platelet Count	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in Platelet count
Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721	Pre-dose and up to 204 days post-dose	PK parameters including clearance rate
Participants With HSCT-TMA Treated With OMS721: 100-day Survival	Study Day of HSCT-TMA diagnosis to 100 days later	Number of participants alive from the date of TMA diagnosis
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in LDH	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in LDH
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Creatine	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in Creatine
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Haptoglobin	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in Haptoglobin
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Hemoglobin	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in Hemoglobin
Participants With HSCT-TMA: Pharmacodynamics (PD)	Pre-dose and up to 204 days post-dose	PD measure is expressed as percentage inhibition of C4d to assess ex-vivo lectin pathway activation
Participants With HSCT-TMA (ADA)	Pre-dose and up to 204 days post-dose	Presence of ADA response. Immunogenicity of multiple-dose administration of OMS721 in subjects with TMA
Participants With HSCT-TMA Treated With OMS721: Overall Survival	Study Day of HSCT-TMA diagnosis to up to 2 years following first dose of OMS721	Survival days from the day of TMA diagnosis

Countries

Belgium, Bulgaria, Hong Kong, Italy, Lithuania, Malaysia, New Zealand, Poland, Singapore, Taiwan, Thailand, United States

Participant flow

Participants by arm

Arm	Count
OMS721 Low Dose Administration of OMS721 at a low dose OMS721	3
OMS721 Medium Dose Administration of OMS721 at a medium dose OMS721	3
OMS721 High Dose Administration of OMS721 at a high dose OMS721	52
Total	58

Withdrawals & dropouts

Period	Reason	FG000	FG002
Overall Study	Adverse Event	1	2
Overall Study	Death	0	9
Overall Study	Deaths based on Long Term Chart Review of HSCT patients	0	10
Overall Study	Proceeded to compassionate use of OMS721	0	1
Overall Study	Withdrawal by Subject	0	3

Baseline characteristics

Characteristic	OMS721 Low Dose	OMS721 Medium Dose	OMS721 High Dose	Total
Age, Categorical <=18 years	0 Participants	1 Participants	0 Participants	1 Participants
Age, Categorical >=65 years	1 Participants	0 Participants	8 Participants	9 Participants
Age, Categorical Between 18 and 65 years	2 Participants	2 Participants	44 Participants	48 Participants
Age, Continuous	45.3 years STANDARD_DEVIATION 17.6	31.7 years STANDARD_DEVIATION 18.7	47.7 years STANDARD_DEVIATION 16.1	46.7 years STANDARD_DEVIATION 16.3
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	2 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants	3 Participants	50 Participants	56 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	0 Participants	13 Participants	14 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) White	2 Participants	3 Participants	35 Participants	40 Participants
Sex: Female, Male Female	2 Participants	1 Participants	21 Participants	24 Participants
Sex: Female, Male Male	1 Participants	2 Participants	31 Participants	34 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	16 / 28	0 / 3	0 / 2	3 / 20	0 / 1	0 / 4
other Total, other adverse events	27 / 28	2 / 3	1 / 2	19 / 20	0 / 1	3 / 4
serious Total, serious adverse events	17 / 28	2 / 3	0 / 2	12 / 20	0 / 1	2 / 4

Outcome results

Primary

Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA

Incidence of treatment-emergent adverse events (AEs): clinically significant changes in vital signs, ECG, and laboratory tests were reported as AEs.

Time frame: Day 1 to 37 days after end of treatment, approximately up to 31 weeks.

Population: 28 participants entered the study with a diagnosis of HSCT-TMA; all participants were in the High Dose Arm

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
OMS721 Low Dose	Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA	0 Participants
OMS721 Medium Dose	Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA	0 Participants
OMS721 High Dose	Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA	27 Participants

Primary

Number of Participants With HSCT-TMA Who Respond to OMS721

Response defined as: Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status

Time frame: Day 1 to up to 2 years following the first dose of OMS721

Population: Only subjects with HSCT-TMA were analyzed; 28 subjects with HSCT were in the Full Analysis Set (FAS)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
OMS721 Low Dose	Number of Participants With HSCT-TMA Who Respond to OMS721	0 Participants
OMS721 Medium Dose	Number of Participants With HSCT-TMA Who Respond to OMS721	0 Participants
OMS721 High Dose	Number of Participants With HSCT-TMA Who Respond to OMS721	17 Participants

Secondary

Participants With HSCT-TMA (ADA)

Presence of ADA response. Immunogenicity of multiple-dose administration of OMS721 in subjects with TMA