Trial Outcomes & Findings for A Study of Erwinaze Administered Intravenously in Patients Who Had an Allergy to Frontline Asparaginase Therapy (NCT NCT01643408)

Last Updated: 2021-06-23

Results Overview

To report the mean 2 day NSAA levels (48 hour levels taken after the 5th dose) that are \> or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

48 hours post-dose 5

Results posted on

2021-06-23

Participant Flow

Participant milestones

Participant milestones
Measure	Safety Population All participants who received at least 1 dose of Erwinaze
Overall Study STARTED	30
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Safety Population All participants who received at least 1 dose of Erwinaze
Overall Study Adverse Event	12
Overall Study Other	2

Baseline Characteristics

A Study of Erwinaze Administered Intravenously in Patients Who Had an Allergy to Frontline Asparaginase Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Safety Population n=30 Participants All patients who received at least one dose of Erwinaze
Age, Continuous	7.9 years STANDARD_DEVIATION 5.08 • n=99 Participants
Sex: Female, Male Female	11 Participants n=99 Participants
Sex: Female, Male Male	19 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants
Race (NIH/OMB) White	25 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants

PRIMARY outcome

Timeframe: 48 hours post-dose 5

Population: The Pharmacokinetic (PK) population consisted of all participants who received at least 1 dose of Erwinaze and were considered evaluable.

Outcome measures

Outcome measures
Measure	Open-Label Erwinaze n=24 Participants asparaginase Erwinia chrysanthemi
Two Day Nadir Serum Asparaginase Activity (NSAA) Level	0.32 (IU/mL) Standard Deviation 0.23

SECONDARY outcome

Timeframe: 48 hours post-dose 5

To report the proportion of participants achieving 2 day NSAA levels (48 hour levels taken after the 5th dose) that are \> or = 0.1 IU/mL during the first 2 weeks of treatment with 3-times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.

Outcome measures

Outcome measures
Measure	Open-Label Erwinaze n=24 Participants asparaginase Erwinia chrysanthemi
Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 48 Hours	20 Participants

SECONDARY outcome

Timeframe: 72 hours post-dose 6

To report the mean 3 day NSAA levels (72 hour levels taken after the 6th dose) that are \> or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.

Outcome measures

Outcome measures
Measure	Open-Label Erwinaze n=21 Participants asparaginase Erwinia chrysanthemi
Three Day NSAA Level	0.09 (IU/mL) Standard Deviation 0.07

SECONDARY outcome

Timeframe: 72 hours post-dose 6

To report the proportion of participants achieving 3 day NSAA levels (72 hour levels taken after the 6th dose) that are \> or = 0.1 IU/mL in the first 2 weeks of treatment with 3 times per week intravenous dosing of Erwinase at 25,000 IU/m2/dose.

Outcome measures

Outcome measures
Measure	Open-Label Erwinaze n=21 Participants asparaginase Erwinia chrysanthemi
Proportion of Participants Achieving Sustained NSAA Values of >0.1 U/mL at 72 Hours	9 Participants

SECONDARY outcome

Timeframe: 4 weeks to 30 weeks

Population: This population consisted of participants who completed Course 4 with Pharmacokinetic(s) (PK) assessments 48 hours after dose 5 (week 8).

To describe the NSAA over time in participants with ALL/Lymphoblastic Lymphoma who have/had developed hypersensitivity to native E. coli asparaginase, Pegaspargase or Calaspargase pegol and are receiving intravenous Erwinaze 3 times per week for a prolonged duration (4-30 weeks).

Outcome measures

Outcome measures
Measure	Open-Label Erwinaze n=6 Participants asparaginase Erwinia chrysanthemi
Nadir Serum Asparaginase Activity Over Time	0.51 IU/mL Standard Deviation 0.252

Adverse Events

Safety Population

Serious events: 15 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Safety Population n=30 participants at risk All participants who received at least 1 dose of Erwinaze
Immune system disorders Hypersensitivity	13.3% 4/30 • 4 Weeks
Gastrointestinal disorders Nausea	3.3% 1/30 • 4 Weeks
Gastrointestinal disorders Vomiting	3.3% 1/30 • 4 Weeks
Blood and lymphatic system disorders Febrile Neutropenia	13.3% 4/30 • 4 Weeks
General disorders Pyrexia	3.3% 1/30 • 4 Weeks
Gastrointestinal disorders Pancreatitis	6.7% 2/30 • 4 Weeks
Musculoskeletal and connective tissue disorders Pain In Extremity	3.3% 1/30 • 4 Weeks
Nervous system disorders Transient Ischaemic Attack	3.3% 1/30 • 4 Weeks
Cardiac disorders Sinus Tachycardia	3.3% 1/30 • 4 Weeks
Blood and lymphatic system disorders Lymphadenitis	3.3% 1/30 • 4 Weeks
Gastrointestinal disorders Stomatitis	3.3% 1/30 • 4 Weeks
Infections and infestations Bacteraemia	3.3% 1/30 • 4 Weeks
Nervous system disorders Posterior Reversible Encephalopathy Syndrome	3.3% 1/30 • 4 Weeks
Skin and subcutaneous tissue disorders Skin Ulcer	3.3% 1/30 • 4 Weeks
Infections and infestations Sepsis	3.3% 1/30 • 4 Weeks
Skin and subcutaneous tissue disorders Urticaria	3.3% 1/30 • 4 Weeks

Other adverse events

Other adverse events
Measure	Safety Population n=30 participants at risk All participants who received at least 1 dose of Erwinaze
Immune system disorders Hypersensitivity	33.3% 10/30 • 4 Weeks
Gastrointestinal disorders Nausea	23.3% 7/30 • 4 Weeks
Gastrointestinal disorders Vomiting	20.0% 6/30 • 4 Weeks
Metabolism and nutrition disorders Hyperglycemia	16.7% 5/30 • 4 Weeks
Blood and lymphatic system disorders Febrile Neutropenia	13.3% 4/30 • 4 Weeks
General disorders Pyrexia	10.0% 3/30 • 4 Weeks
Investigations Alanine Aminotransferase Increased	10.0% 3/30 • 4 Weeks
Gastrointestinal disorders Pancreatitis	6.7% 2/30 • 4 Weeks
Gastrointestinal disorders Stomatitis	6.7% 2/30 • 4 Weeks

Additional Information

Director, Disclosure & Transparency

Jazz Pharmaceuticals

Phone: 2158709177

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.
Publication restrictions are in place

Restriction type: OTHER