Trial Outcomes & Findings for A Clinical Study of SHP674 (Pegaspargase) in Participants With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia (NCT NCT04067518)

Last Updated: 2023-04-20

Results Overview

An adverse event (AE) is defined as any untoward medical occurrence in a participant after signing informed consent. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not it is related to the investigational product. TEAE is defined as any untoward medical occurrence in a participant who received an investigational product which occurs during the period from Day 1 of the pre-treatment phase to 30 (+7) days after the last dose of investigational product, or until the start of a new therapy, whichever occurs first. A related adverse event signifies that there is a reasonable causal relationship between study treatment and an AE.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Up to 30 days after last dose of study drug (approximately 49 weeks)

Results posted on

2023-04-20

Participant Flow

Participants were enrolled at 8 investigative sites in Japan from 17 October 2019 to 18 January 2021. Data is reported up to primary completion date, 12 February 2021.

A total of 28 participants were enrolled, 3 into Part 1 and 25 into Part 2, of which 26 participants were treated, 3 in Part 1 and 23 in Part 2.

Participant milestones

Participant milestones
Measure	Part 1: SHP674 Participants with ALL who were stratified into the standard risk (SR) or intermediate risk (IR) groups received total 3 doses of SHP674, 2500 international units per square meter (IU/m\^2) (if body surface area \[BSA\] ≥0.6 m\^2) or 82.5 international units per kilogram (IU/kg) (if BSA \<0.6 m\^2) intravenously (IV) on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period. Participants with ALL who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Overall Study STARTED	3	25
Overall Study Safety Analysis Set	3	23
Overall Study - Standard Risk(SR)/Intermediate Risk (IR)	3	21
Overall Study - Hihg Risk (HR)	0	1
Overall Study - Missing	0	1
Overall Study Full Analysis Set	0	23
Overall Study Immunogenicity Analysis Set	3	22
Overall Study Pharmacokinetic Analysis Set	3	23
Overall Study COMPLETED	2	20
Overall Study NOT COMPLETED	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: SHP674 Participants with ALL who were stratified into the standard risk (SR) or intermediate risk (IR) groups received total 3 doses of SHP674, 2500 international units per square meter (IU/m\^2) (if body surface area \[BSA\] ≥0.6 m\^2) or 82.5 international units per kilogram (IU/kg) (if BSA \<0.6 m\^2) intravenously (IV) on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period. Participants with ALL who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Overall Study Adverse Event	1	3
Overall Study Screen failures	0	1
Overall Study Enrolled but not treated	0	1

Baseline Characteristics

A Clinical Study of SHP674 (Pegaspargase) in Participants With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: SHP674 n=3 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 n=23 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.	Total n=26 Participants Total of all reporting groups
Age, Continuous	10.2 years STANDARD_DEVIATION 2.63 • n=93 Participants	6.7 years STANDARD_DEVIATION 4.79 • n=4 Participants	7.1 years STANDARD_DEVIATION 4.70 • n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	11 Participants n=4 Participants	13 Participants n=27 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	12 Participants n=4 Participants	13 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	3 Participants n=93 Participants	23 Participants n=4 Participants	26 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment Japan	3 participants n=93 Participants	23 participants n=4 Participants	26 participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 30 days after last dose of study drug (approximately 49 weeks)

Population: SAF (Safety Analysis Set) included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As pre-specified in the protocol, this outcome measure is analyzed only for Part 1.

Outcome measures

Outcome measures
Measure	Part 1: SHP674 n=3 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period TEAEs	3 Participants	—
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period SHP-674-Related TEAEs	3 Participants	—

PRIMARY outcome

Timeframe: 14 days after the first dose of SHP674

Population: FAS (Full Analysis Set) included all participants who were enrolled and received SHP674 in Part 2 of the study.

Outcome measures

Outcome measures
Measure	Part 1: SHP674 n=23 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674	100.0 participants Interval 85.2 to 100.0	—

SECONDARY outcome

Timeframe: Predose and 25 days post dose (Part 1 and Part 2)

Population: Immunogenicity analysis set (IMAS) included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study and had at least one evaluable post-dose sample. If the pre-dose sample was missing it was considered negative.

Outcome measures

Outcome measures
Measure	Part 1: SHP674 n=3 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 n=22 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2) Pre-existing ADA positive	0 Participants	4 Participants
Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2) Seroconversion upon tretament	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Predose and 25 days post dose (Part 1 and part 2)

Outcome measures

Outcome measures
Measure	Part 1: SHP674 n=3 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 n=22 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2) Pre-existing Anti-PEG positive	0 Participants	2 Participants
Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2) Seroconversion upon treatment	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 14 days after the first dose of SHP674

Population: SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As pre-specified in the protocol, this outcome measure is analyzed only for Part 1.

Outcome measures

Outcome measures
Measure	Part 1: SHP674 n=3 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674	100.0 percentage of participants Interval 29.2 to 100.0	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose, 5 min, 4 hours, 24 hours post dose), Days 2, 4, 11, 14, 18, 25 post dose

Population: FAS included all participants who were enrolled and received SHP674 in Part 2 of the study. Number analyzed indicates the number of participants analyzed at the specified timepoint.

Outcome measures

Outcome measures
Measure	Part 1: SHP674 n=23 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL: Day 1 (4 hours post dose)	0.0 percentage of participants Interval 0.0 to 14.8	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 1 (pre-dose)	0.0 percentage of participants Interval 0.0 to 14.8	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 1 (5 mins post dose)	100.0 percentage of participants Interval 84.6 to 100.0	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 1 (4 hours post dose)	100.0 percentage of participants Interval 85.2 to 100.0	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 1 (24 hours post dose)	100.0 percentage of participants Interval 85.2 to 100.0	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 2 post dose	100.0 percentage of participants Interval 85.2 to 100.0	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 4 post dose	100.0 percentage of participants Interval 85.2 to 100.0	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 11 post dose	100.0 percentage of participants Interval 85.2 to 100.0	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 14 post dose	100.0 percentage of participants Interval 85.2 to 100.0	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 18 post dose	95.5 percentage of participants Interval 77.2 to 99.9	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL ≥0.1 IU/mL: Day 25 post dose	50.0 percentage of participants Interval 28.2 to 71.8	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL : Day 1 (pre-dose)	100.0 percentage of participants Interval 85.2 to 100.0	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL: Day 1 (5 mins post dose)	0.0 percentage of participants Interval 0.0 to 15.4	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL: Day 1 (24 hours post dose)	0.0 percentage of participants Interval 0.0 to 14.8	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL: Day 2 post dose	0.0 percentage of participants Interval 0.0 to 14.8	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL: Day 4 post dose	0.0 percentage of participants Interval 0.0 to 14.8	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL: Day 11 post dose	0.0 percentage of participants Interval 0.0 to 14.8	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL: Day 14 post dose	0.0 percentage of participants Interval 0.0 to 14.8	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL: Day 18 post dose	4.5 percentage of participants Interval 0.1 to 22.8	—
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL <0.1 IU/mL: Day 25 post dose	50.0 percentage of participants Interval 28.2 to 71.8	—

SECONDARY outcome

Timeframe: 1 year after the start of study treatment (from first dose up to 12 months)

Population: The analysis was performed on the safety set analysis, defined as the set of all subjects who had received at least one dose of SHP674 in Part 1 or Part 2 of the study.

Survival rate is defined as the percentage of subjects who survived at 1 year after the start of study treatment.

Outcome measures

Outcome measures
Measure	Part 1: SHP674 n=3 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 n=23 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Survival Rate at 1 Year After the Start of Study Treatment	3 Participants	23 Participants

SECONDARY outcome

Timeframe: 1 year after the start of study treatment (from first dose up to 12 months)

Population: The analysis was performed on the safety set analysis, defined as the set of all subjects who had received at least one dose of SHP674 in Part 1 or Part 2 of the study.

Event-free survival rate is defined as percentage of subjects who did not experience any event and survived at 1 year after the start of study treatment.

Outcome measures

Outcome measures
Measure	Part 1: SHP674 n=3 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 n=23 Participants Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Event-free Survival Rate at 1 Year After the Start of Study Treatment	3 Participants	23 Participants

Adverse Events

Part 1: SHP674

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 2: SHP674

Serious events: 10 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: SHP674 n=3 participants at risk Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period.	Part 2: SHP674 n=23 participants at risk Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
General disorders Pyrexia	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Immune system disorders Haemophagocytic lymphohistiocytosis	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Infections and infestations Cellulitis	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Infections and infestations Device related infection	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Infections and infestations Gastroenteritis	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Infections and infestations Sepsis	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Infections and infestations Septic shock	33.3% 1/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	0.00% 0/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Injury, poisoning and procedural complications Anaphylactic transfusion reaction	33.3% 1/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	0.00% 0/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Investigations Platelet count decreased	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.
Nervous system disorders Posterior reversible encephalopathy syndrome	0.00% 0/3 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.	4.3% 1/23 • Parts 1 and 2: Up to 30 days after last dose of study drug (approximatively 117 weeks) SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As planned and pre-specified in protocol, the safety data was analyzed for Part 1 and Part 2 of study.

Other adverse events

Additional Information

Clinical Studies Department

Institut de Recherches Internationales Servier

Phone: +33 1 55 72 43 66

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding study results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER