Trial Outcomes & Findings for Treatment of Hemoglobin SC Disease With Hydroxyurea (NCT NCT02336373)

NCT ID: NCT02336373

Last Updated: 2020-09-09

Results Overview

Mean change in PedsQL™ Sickle Cell Disease Module version 3.0 score after achieving MTD compared with baseline. PedsQL™ Sickle Cell Disease Module version 3.0 scores are on a 100 point scale ranging from 0 to 100 with higher values indicating better quality of life. PedsQL: pediatric qulaity of life

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 32 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2020-09-09

Participant Flow

Participant milestones

Measure	Hydroxurea Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores
Overall Study STARTED	32
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Measure	Hydroxurea Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores
Overall Study Protocol closed early	4
Overall Study Physician Decision	14

Baseline Characteristics

Treatment of Hemoglobin SC Disease With Hydroxyurea

Baseline characteristics by cohort

Measure	Hydroxyurea n=32 Participants hydroxyurea (HU) at 10 mg/kg daily
Age, Categorical <=18 years	32 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	11 years STANDARD_DEVIATION 3.5 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	31 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants
PedsQLTM 3.0 SCD Module score	54.9 units on a scale STANDARD_DEVIATION 20.4 • n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Participants who achieved MTD of hydroxyureq per protocol with observed PEDSQL scores at 6-months and baseline (study entry).

Mean change in PedsQL™ Sickle Cell Disease Module version 3.0 score after achieving MTD compared with baseline.

PedsQL™ Sickle Cell Disease Module version 3.0 scores are on a 100 point scale ranging from 0 to 100 with higher values indicating better quality of life.

PedsQL: pediatric qulaity of life

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in PedsQL SCDM

5.7 Score on PedsQL 3.0 SCD Module Standard Deviation 15.5

SECONDARY outcome

Timeframe: up to 7 months

Change in hematocrit to viscosity ratio (HVR) at 45s-1 at follow-up versus baseline. This is a measure of oxygen carrying capacity, as a higher hematocrit with lower viscosity indicates ability to deliver oxygen without slowed blood flow due to high viscosity or blood thickness. Higher values are associated with improvement.

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in HVR at 45s-1

0.083 au Standard Deviation 0.72

SECONDARY outcome

Timeframe: up to 7 months

Change in hematocrit viscosity ratio at 225s

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in HVR at 225s-1

0.11 au Standard Deviation 0.83

SECONDARY outcome

Timeframe: up to 7 months

Change in percent dense red blood cells

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

DRBC

1.93 percentage of dense red blood cells Standard Deviation 20.6

SECONDARY outcome

Timeframe: up to 7 months

Change in fetal hemaglobin

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in HbF

-0.47 percent Standard Deviation 0.94

SECONDARY outcome

Timeframe: up to 7 months

Change in mean corpuscular volume

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in MCV

-6.2 fL Standard Deviation 2.3

SECONDARY outcome

Timeframe: up to 7 months

Change in mean corpuscular hemoglobin concentration

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in MCHC

0.33 percent Standard Deviation 0.43

SECONDARY outcome

Timeframe: up to 7 months

Change in hemoglobin

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in Hb

-0.62 percent Standard Deviation 0.59

SECONDARY outcome

Timeframe: up to 7 months

Change in absolute reticulocyte count

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in ARC

0.01 10^3 cells/uL Standard Deviation 0.025

SECONDARY outcome

Timeframe: up to 7 months

Change in absolute neutrophil count

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in ANC

-0.24 10^3 cells/uL Standard Deviation 0.82

SECONDARY outcome

Timeframe: up to 7 months

Change in lactate dehydrogenase

Outcome measures

Measure

Hydroxurea n=6 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in LDH

-21.7 percent Standard Deviation 52.48

SECONDARY outcome

Timeframe: up to 7 months

Change in unconjugated bilirubin levels

Outcome measures

Measure

Hydroxurea n=5 Participants Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase. hydroxyurea: Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores

Change in UB Levels

-0.1 percent Standard Deviation 0.28

Adverse Events

Hydroxurea

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Vivien Sheehan, MD, PhD

Baylor College of Medicine

Phone: (832) 824-4459

Email: vxsheeha@txch.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place