A Study of Rilzabrutinib in Adult Patients With Immune Thrombocytopenia (ITP)

The percentage of participants who achieved 2 or more consecutive platelet counts, separated by at least 5 days, of >=50,000/ microliter (μL) and an increase of platelet count of >=20,000/μL from baseline, by starting dose level and overall, without use of rescue medication in the 4 weeks prior to the latest elevated platelet count. 95% confidence interval (CI) was based on the Clopper-Pearson method. The average of the 2 screening results and the Cycle 1 Day 1 result were used as the baseline value.

The percentage of participants who achieved platelet counts >=50,000/μL on at least 8 out of the last 12 weeks of the 24-week treatment period without the use of rescue medication after 10 weeks of active treatment. 95% CI was based on the Clopper-Pearson exact method.

Adverse event (AE): any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of rilzabrutinib, whether or not considered related to rilzabrutinib. TEAEs: AEs that developed or worsened or became serious on or after the first dose administration of rilzabrutinib (Day 1). Any TEAEs are considered treatment-related TEAEs as per Investigator's evaluation of participant's circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an TEAE can be considered as related to the rilzabrutinib.

AE any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of rilzabrutinib, whether or not considered related to rilzabrutinib. TEAEs: AEs that developed or worsened or became serious during the treatment-emergent period, defined as any time after the first dose administration of rilzabrutinib (Day 1). Any TEAEs are considered treatment-related TEAEs as per Investigator's evaluation of participant's circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an TEAE can be considered as related to rilzabrutinib.

The percentage of weeks in which participants achieved platelet counts >=50,000/μL in the treatment period are summarized here.

The percentage of participants who had at least 4 out of the final 8 platelet counts >=50,000/μL are summarized here. The final 8 scheduled platelet counts are the measurements performed in the last 8 weeks of rilzabrutinib (depending on treatment duration, not necessarily from Week 19 to Week 24) in the treatment period. 95% CI was based on the Clopper-Pearson method.

Average of post Day 1 platelet count is equivalent to average of (average of each participant's post-Day 1 platelet counts), included platelet counts up to 1 day after the date of last dose of rilzabrutinib and excluded platelet counts on or after date of rescue, if applicable. The average of the 2 screening results and the Cycle 1 Day 1 result measured on different date were used as the baseline value.

The number of weeks in which participant achieved platelet counts >=50,000/μL in the treatment period are summarized here. The number of weeks is based on the number of scheduled weekly assessments, by study day.

The number of weeks in which participant achieved platelet counts >=30,000/μL in the treatment period are summarized here. The number of weeks is based on the number of scheduled weekly assessments, by study day.

Time to first platelet count >=50,000/μL during the treatment period in days was calculated as: (date of first occurrence of platelet count >=50,000/μL - date of first rilzabrutinib dosing) +1.

The number of weeks in which participant achieved platelet counts with thresholds as: >=50,000/μL or >=30,000/μL and doubling the baseline in the absence of rescue therapy (platelet counts will be censored for 4 weeks after the use of rescue medication, if given) are summarized here. Baseline is defined as the average of 3 platelet counts: 2 qualified screening platelet counts collected in electronic case report form (eCRF) and Week 1 (study day 1) platelet count.

Percentage of participants who achieved 2 or more consecutive platelet counts, separated by at least 5 days, of >=50,000/μL and an increase of platelet count of >=20,000/μL from baseline without use of rescue medication in the 4 weeks prior to the latest elevated platelet count are summarized here. Baseline is defined as the average of 3 platelet counts: 2 qualified screening platelet counts collected in eCRF and Week 1 (study day 1) platelet count. 95% CI was based on the Clopper-Pearson exact method.

The number of weeks in which participant achieved platelet counts >=30,000/μL and doubling the baseline in the absence of rescue therapy (platelet counts will be censored for 4 weeks after the use of rescue medication, if given) are summarized here. Baseline is defined as the average of 3 platelet counts: 2 qualified screening platelet counts collected in eCRF and Week 1 (study day 1) platelet count.

Rescue medication is defined as any therapy used to rescue a participant (1 of intravenous immunoglobulin [IVIG], high-dose steroids, platelet infusion or anti-D immunoglobulin infusion). Percentage of participants who received rescue medication are summarized here. 95% CI was based on the Clopper-Pearson exact method.

The IBLS is a bleeding assessment score. IBLS comprises of 11 sites for female and 10 sites for male, and each site is scored from 0 (none) to 2 (marked bleeding). The total overall score ranges from 0-22, with higher scores indicating higher presence of marked bleeding. For each participant, an IBLS score at each visit was calculated by taking the average across 11 items (10 for male and postmenopausal women) at 9 anatomical sites (8 for male and postmenopausal women). For each participant, a mean IBLS score was also calculated by taking the average across all post-baseline visits during the 24-week treatment period. IBLS average value ranges from 0 to 2. The smaller the IBLS average value is, the healthier the participants are. For change from baseline, negative value indicates an improvement. The baseline value is defined as the last available value before the first dose rilzabrutinib.

Rescue medication is defined as any therapy used to rescue a participant (1 of IVIG, high-dose steroids, platelet infusion or anti-D immunoglobulin infusion). The percentage of participants who received rescue medication for each dose level and overall are summarized here. 95% CI was based on the Clopper-Pearson method.

The percentage of participants with intensity grade 2 or higher bleeding event are summarized for each dose level and overall. The TEAEs with standardized medical dictionary for regulatory activities (MedDRA) query (SMQ) hemorrhages were medically determined for analysis of bleeding events. 95% CI was based on the Clopper-Pearson method.

The ITP-BAT scale comprises of 11 grades from 0 (none) to 2 (marked bleeding), with higher scores indicating higher presence of marked bleeding, assessed at 9 anatomical sites (skin, oral, epistaxis, gastrointestinal [GI], urinary, gynecological [GYN], pulmonary, intracranial hemorrhage [HEM], subconjunctival HEM) by history over the previous week (Hx). In addition, 2 sites (skin and oral), were also assessed by physical examination (PE). The 'worst ever' bleeding experienced at each site was graded using the same system. Here, 0 indicates none; 1 indicates 1-5 bruises and/or scattered petechiae and 2 indicates >5 bruises with size >2 centimeter (cm) and/or diffuse petechiae. Each participant summed up the transformed scores across all 11 sites per visit assessment. The total overall score ranges from 0-22 with the higher score indicating worst outcome.

Plasma samples were collected at specified timepoints to determine Cmax of rilzabrutinib.

Plasma samples were collected at specified timepoints to determine tmax of rilzabrutinib.

Plasma samples were collected at specified timepoints to determine AUClast of rilzabrutinib.

Plasma samples were collected at specified timepoints to determine AUCinf of rilzabrutinib.

Plasma samples were collected at specified timepoints to determine t1/2 of rilzabrutinib.

Plasma samples were collected at specified timepoints to determine Vz/F of rilzabrutinib.

Plasma samples were collected at specified timepoints to determine CL/F of rilzabrutinib.

Plasma samples were collected at specified timepoints for evaluation of rilzabrutinib pharmacokinetic (PK) concentrations.