Trial Outcomes & Findings for Adenosine 2A Agonist Lexiscan in Children and Adults With Sickle Cell Disease (NCT NCT01085201)
NCT ID: NCT01085201
Last Updated: 2014-03-07
Results Overview
Per protocol, Lexiscan was considered "safe" if well tolerated based on number of DLTs reported. Stage 1 of the study was a 3+3 dose escalation study. Three doses were tested: 0.24 mcg/kg/hr (dose level 0), 0.6 mcg/kg/hr (dose level 1), and 1.44 mcg/kg/hr (dose level 2). Dose escalation continued until 6 participants were treated at the maximum planned dose (dose level 2). We studied a total of 15 patients in Stage 1. In Stages 2 and 3, if at least 2/3 participants tolerated the dose, an additional 3 participants were studied. We studied 6 participants in each of stages 2 and 3. In stage 2b, Lexiscan was studied for a longer (48 hr) duration in 3 participants. In stage 4, Lexiscan was studied in 3 pediatric participants.
COMPLETED
PHASE1
39 participants
30 to 54 hours plus 30-day follow-up
2014-03-07
Participant Flow
Recruitment began on 4/19/10 and ceased completely on 3/26/13. In Stages 1, 2 and 2b, patients were recruited from the medical clinic. For Stages 3 and 4, in which subjects were treated during a pain crisis hospitalization, patients were first informed about the study in clinic, and reminded about the study after being admitted.
Patients who were assigned to Stages 1, 2 or 2b, in which subjects were studied at baseline (i.e. not in pain crisis), could be excluded if they experienced a pain crisis in the interim period between enrollment and their scheduled study date.
Participant milestones
| Measure |
Stage 1
12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2
24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2B
48-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 3
24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 4
24-hour infusion to children with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
18
|
7
|
5
|
6
|
3
|
|
Overall Study
COMPLETED
|
15
|
6
|
3
|
6
|
3
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
2
|
0
|
0
|
Reasons for withdrawal
| Measure |
Stage 1
12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2
24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2B
48-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 3
24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 4
24-hour infusion to children with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
|---|---|---|---|---|---|
|
Overall Study
Scheduling conflict
|
1
|
0
|
1
|
0
|
0
|
|
Overall Study
Unknown- no study drug
|
2
|
0
|
0
|
0
|
0
|
|
Overall Study
Fond ineligible after consent
|
0
|
1
|
1
|
0
|
0
|
Baseline Characteristics
Adenosine 2A Agonist Lexiscan in Children and Adults With Sickle Cell Disease
Baseline characteristics by cohort
| Measure |
Stage 1
n=15 Participants
12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2
n=6 Participants
24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2B
n=3 Participants
48-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 3
n=6 Participants
24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 4
n=3 Participants
24-hour infusion to children with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
30 Participants
n=10 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Age, Continuous
|
33.71 years
STANDARD_DEVIATION 10.49 • n=5 Participants
|
33.84 years
STANDARD_DEVIATION 8.75 • n=7 Participants
|
23.68 years
STANDARD_DEVIATION 5.05 • n=5 Participants
|
31.61 years
STANDARD_DEVIATION 6.42 • n=4 Participants
|
16.77 years
STANDARD_DEVIATION 0.89 • n=21 Participants
|
30.9 years
STANDARD_DEVIATION 9.86 • n=10 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
18 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
15 Participants
n=10 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
6 participants
n=7 Participants
|
3 participants
n=5 Participants
|
6 participants
n=4 Participants
|
3 participants
n=21 Participants
|
33 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: 30 to 54 hours plus 30-day follow-upPopulation: The number of participants was determined per protocol following a 3+3 design. In Stages 2b and 4, we received permission from the FDA, IRB, and DSMB to study only 3 subjects because we did not observe any prior DLT. One patient enrolled in Stage 2b withdrew consent during the infusion due to an unrelated toothache, and was excluded from analysis.
Per protocol, Lexiscan was considered "safe" if well tolerated based on number of DLTs reported. Stage 1 of the study was a 3+3 dose escalation study. Three doses were tested: 0.24 mcg/kg/hr (dose level 0), 0.6 mcg/kg/hr (dose level 1), and 1.44 mcg/kg/hr (dose level 2). Dose escalation continued until 6 participants were treated at the maximum planned dose (dose level 2). We studied a total of 15 patients in Stage 1. In Stages 2 and 3, if at least 2/3 participants tolerated the dose, an additional 3 participants were studied. We studied 6 participants in each of stages 2 and 3. In stage 2b, Lexiscan was studied for a longer (48 hr) duration in 3 participants. In stage 4, Lexiscan was studied in 3 pediatric participants.
Outcome measures
| Measure |
Stage 1 - Dose Levels 0, 1 and 2
n=15 Participants
12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2 - Dose Level 2
n=6 Participants
24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2B - Dose Level 2
n=3 Participants
48-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 3 - Dose Level 2
n=6 Participants
24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 4 - Dose Level 2
n=3 Participants
24-hour infusion to children with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
|---|---|---|---|---|---|
|
Dose Limiting Toxicities as a Measure of Whether Infusional Lexiscan is Safe in Individuals With SCD.
|
1 number of DLT
|
0 number of DLT
|
0 number of DLT
|
0 number of DLT
|
0 number of DLT
|
SECONDARY outcome
Timeframe: pre-drug to 54 hoursPopulation: The number of subjects was determined per protocol. Stage 1 was excluded as the goal was to determine the optimal markers for iNKT cells. Only 4 subjects were analyzed in Stage 2 because 24-hour samples were not obtained for 2 subjects. Stages 2b and 4 were not completely analyzed because these stages were completed early after studying 3 subjects.
Percentage of activated iNKT cells after receiving a 24-hour infusion of Lexiscan was compared to pre-drug. iNKT cell activation was evaluated using antibodies targeting the p65 subunit of nuclear factor-kappa B (phospho-NF-kB p65). Measures are given as percentage of change in phospho-NF-kB p65 activation in iNKT cells compared to pre-drug after a 24-hour infusion. iNKT cell activation in Stages 1, 2b, and 4 was not analyzed (see analysis population description).
Outcome measures
| Measure |
Stage 1 - Dose Levels 0, 1 and 2
12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2 - Dose Level 2
n=4 Participants
24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2B - Dose Level 2
48-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 3 - Dose Level 2
n=6 Participants
24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 4 - Dose Level 2
24-hour infusion to children with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
|---|---|---|---|---|---|
|
Percentage of Activated iNKT Cells and/or Activation Markers on iNKT Cells in Individuals With SCD.
|
—
|
-3 percentage of change in activation
Standard Deviation 0.30
|
—
|
-48 percentage of change in activation
Standard Deviation 0.30
|
—
|
SECONDARY outcome
Timeframe: pre-drug to 54 hoursPopulation: The number of participants was determined per protocol following a 3+3 design. Stages 1, 2 and 2b were excluded because this outcome measure is specific to the experience of a vaso-occlusive event, which was studied in Stages 3 and 4.
Pain was measured using a standardized pain scale. The scale is a 10-cm visual analogue scale (10 cm-long line printed on white paper), where 0 is no pain and 10 is maximum pain. Participants were asked to indicate their pain level by marking on the line prior to each blood draw.
Outcome measures
| Measure |
Stage 1 - Dose Levels 0, 1 and 2
12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2 - Dose Level 2
24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2B - Dose Level 2
48-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 3 - Dose Level 2
n=6 Participants
24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 4 - Dose Level 2
n=3 Participants
24-hour infusion to children with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
|---|---|---|---|---|---|
|
Pain Levels During a Vaso-occlusive Event in Children and Adults With SCD.
|
—
|
—
|
—
|
5.8 units on a scale
Standard Deviation 0.8
|
7.8 units on a scale
Standard Deviation 1.1
|
Adverse Events
Stage 1 - Dose Levels 0, 1 and 2
Stage 2 - Dose Level 2
Stage 2B - Dose Level 2
Stage 3 - Dose Level 2
Stage 4 - Dose Level 2
Serious adverse events
| Measure |
Stage 1 - Dose Levels 0, 1 and 2
n=15 participants at risk
12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2 - Dose Level 2
n=6 participants at risk
24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 2B - Dose Level 2
n=3 participants at risk
48-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 3 - Dose Level 2
n=6 participants at risk
24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
Stage 4 - Dose Level 2
n=3 participants at risk
24-hour infusion to children with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Lexiscan : Given as an infusion
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Sickle cell crisis with prolonged hospitalization - Grade 2
|
0.00%
0/15 • 3 years
|
16.7%
1/6 • Number of events 1 • 3 years
|
0.00%
0/3 • 3 years
|
0.00%
0/6 • 3 years
|
0.00%
0/3 • 3 years
|
|
Blood and lymphatic system disorders
Uncomplicated vaso-occlusive crisis requiring hospitalization - Grade 3
|
0.00%
0/15 • 3 years
|
16.7%
1/6 • Number of events 2 • 3 years
|
0.00%
0/3 • 3 years
|
16.7%
1/6 • Number of events 1 • 3 years
|
0.00%
0/3 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Rib pain, leading to hospitalization - Grade 3
|
0.00%
0/15 • 3 years
|
0.00%
0/6 • 3 years
|
0.00%
0/3 • 3 years
|
16.7%
1/6 • Number of events 1 • 3 years
|
0.00%
0/3 • 3 years
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place