Primary Immune Thrombocytopenia
Conditions
Keywords
ITP, UCB7665, Rozanolixizumab, Primary immune thrombocytopenia
Brief summary
The purpose of this study is to demonstrate the clinical efficacy of rozanolixizumab in maintenance treatment and assess safety and tolerability of rozanolixizumab in adult study participants with primary immune thrombocytopenia (ITP).
Interventions
DRUGRozanolixizumab
Study participants receive rozanolixizumab by subcutaneous infusion at pre-specified time points.
OTHERPlacebo
Study participants receive placebo by subcutaneous infusion at pre-specified time points.
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigators are blinded to the treatment code, they will see the platelet values.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Study participant must be ≥18 years of age at the time of the Screening Visit * Study participant has a diagnosis of persistent (\>3 months duration) or chronic (\>12 months duration) primary immune thrombocytopenia (ITP) at the Screening Visit * Study participant has a documented intolerance or insufficient response to two or more appropriate standard of care ITP treatments prior to Screening * Study participants must have prior history of a response to a previous ITP therapy * If taking allowed drugs, study participant must be on stable doses during defined time periods prior to Baseline (Day 1) * Study participant has a documented history of low platelet count (\<30×10\^9/L) prior to Screening * Study participant has a platelet count measurement at Screening and at Baseline (Day 1) with an average of the two \<30×10\^9/L and no single count may be \>35×10\^9/L (using local laboratories) * Study participant has a current or history of a peripheral blood smear consistent with ITP * Study participants may be male or female: 1. A male participant must agree to use contraception during the Treatment Period and for at least 3 months after the final dose of study treatment and refrain from donating sperm during this period 2. A female participant is eligible to participate if she is not pregnant as confirmed by a negative serum pregnancy test and not planning to get pregnant during the participation in the study, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the Treatment Period and for at least 3 months after the dose of study treatment
Exclusion criteria
* Participant has a history of arterial or venous thromboembolism (eg, stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism) within the 6 months prior to randomization or requires current anticoagulant treatment * Study participant has clinically significant bleeding that warrants immediate platelet adjustment (eg, menorrhagia with significant drop in hemoglobin) * Study participant has a known hypersensitivity to any components of the study medication or any other anti-neonatal Fc receptor (FcRn) medications * Study participant has evidence of a secondary cause of immune thrombocytopenia (clear association with other medical conditions, eg, untreated H. pylori infection, leukemia, lymphoma, common variable immunodeficiency, systemic lupus erythematosus, autoimmune thyroid disease or is drug induced), participant has a multiple immune cytopenia (eg, Evan's syndrome) * Study participant has a clinically relevant active infection (eg, sepsis, pneumonia, or abscess) in the opinion of the investigator, or had a serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to the first dose of investigational medicinal product (IMP) * Study participant with a known tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent tuberculosis infection (LTBI), or current/history of nontuberculous mycobacterial infection (NTMBI) * Study participant has a history of a major organ transplant or hematopoietic stem cell/marrow transplant * Study participant has experienced intracranial bleed in the last 6 months prior to the Screening Visit * Study participant has a history of coagulopathy disorders other than ITP * Study participant with current or medical history of immunoglobulin A (IgA) deficiency, or a measurement of IgA \<50 mg/dL at the Screening Visit * Study participant has undergone a splenectomy in the 2 years prior to the Baseline Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Durable Clinically Meaningful Platelet Response of ≥50x10^9/L, for at Least 8 Out of 12 Weeks During the Last 12 Weeks | During the last 12 weeks (Week 13 to Week 25) | Percentage of Participants With Durable Clinically Meaningful Platelet Response of ≥50×10\^9/L, for at least 8 out of 12 weeks during the last 12 weeks were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Clinically Meaningful Platelet Response (CMPR) of ≥50×10^9/L: Time From Starting Treatment to Achievement of First Response of ≥50×10^9/L | Time from starting treatment to achievement of first response of ≥50×10^9/L (up to Week 25) | Time from starting treatment to achievement of first Clinically Meaningful Platelet Response of ≥50×10\^9/L was defined as date of first clinically meaningful response - date of first treatment + 1. Median was calculated based upon the Kaplan-Meier estimate. |
| Percentage of Participants With Clinically Meaningful Platelet Response of ≥50×10^9/L by Day 8 | Baseline to Day 8 | Clinically meaningful platelet response was defined as platelet count of ≥50×10\^9/L. |
| Percentage of Participants With Response Defined as Platelet Count ≥30*10^9/L and at Least Doubling of Baseline, at Least 2 Separate Occasions at Two Adjacent Nominal Visits at Least 7 Days Apart, and Absence of Bleeding | From Baseline during Treatment Period (up to Week 25) | Response was defined as platelet count ≥30×10\^9/L and at least doubling of baseline, at least 2 separate occasions at two adjacent nominal visits at least 7 days apart, and absence of bleeding. |
| Cumulative Number of Weeks With Clinically Meaningful Platelet Response of ≥50×10^9/L Over the 24-week Treatment Period | Week 1 up to Week 25 | Total number of weeks with platelet counts ≥50×10\^9/L over the 24-week Treatment Period of the study (Week 1 to Week 25) were reported. |
| Change From Baseline to Week 25 in Primary Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) Symptoms Score | From Baseline during Treatment Period (up to Week 25) | The ITP-PAQ Version 1 is a 44 item disease-specific Health-Related Quality of Life questionnaire developed for use in adults with chronic ITP. It includes 10 scales, Four of the scales measure physical health: Symptoms (6 items), Bother (3 items), Fatigue (4 items), and Activity (2 items). Two of the scales measure emotional health: Fear (5 items) and Psychological (5 items) Health. The remaining four scales measure other aspects of quality of life (QOL): Work QOL (4 items), Social QOL (4 items), Women's Reproductive QOL (6 items) and Overall QOL (5 items). Each item is rated on a Likert-type scale containing 4 to 7 responses. All item scores are transformed to a 0 to 100 continuum and are weighted equally to derive individual scale scores and the total score (0-100) is calculated as per the formula: Sum of item scores within the scale/raw sum range\*100. Higher scores indicate better health status. |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | From Baseline to end of Safety Follow-Up Period (up to Week 31) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. TEAEs are defined as AEs starting after the time of first IMP administration up to and including 8 weeks (56 days) after the final dose. |
| Percentage of Participants With TEAEs Leading to Withdrawal of Investigational Medicinal Product (ie, Study Discontinuation) | From Baseline to end of Safety Follow-Up Period (up to Week 31) | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. TEAEs are defined as AEs starting after the time of first IMP administration up to and including 8 weeks (56 days) after the final dose. |
| Time to First Rescue Therapy | From Baseline to first rescue therapy (up to Week 25) | Time to first rescue therapy was defined as date of first rescue therapy use - date of first treatment + 1. Median was calculated based upon the Kaplan-Meier estimate. The probability of requiring rescue medication did not reach 0.5 so the KM median in the rozanolixizumab arm could not be estimated. |
Countries
Bulgaria, France, Georgia, Greece, Hungary, Italy, Japan, Moldova, Poland, Romania, Russia, South Korea, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study started to enroll study participants in Jan 2020 and terminated on April 2022.
Pre-assignment details
Participant Flow refers to the Randomized Set.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a fixed-unit starting dose of placebo sc infusion matched to rozanolixizumab Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of placebo sc infusion matched to rozanolixizumab Dose B every 2 weeks until Week 23. Participants were followed up to a maximum of Week 31. | 12 |
| Rozanolixizumab Participants received a fixed-unit starting dose of rozanolixizumab sc infusion equivalent to Dose A on Day 1. Following the initial dose, participants received a fixed-unit dose of rozanolixizumab sc infusion equivalent to Dose B every 2 weeks until Week 23. After protocol amendment 3, the starting dose was removed and the frequency of administration of the Dose B was changed to weekly. Participants were followed up to a maximum of Week 31. | 21 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administration of Rescue and concern about IMP | 0 | 1 |
| Overall Study | Adverse event, non-fatal | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Rozanolixizumab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 18 Participants | 28 Participants |
| Age, Continuous | 51.4 years STANDARD_DEVIATION 15.9 | 41.4 years STANDARD_DEVIATION 12.8 | 45.1 years STANDARD_DEVIATION 14.6 |
| Platelet count | 17.2 cells*10^9/L STANDARD_DEVIATION 11.3 | 17.0 cells*10^9/L STANDARD_DEVIATION 9.4 | 17.1 cells*10^9/L STANDARD_DEVIATION 9.9 |
| Race/Ethnicity, Customized Asian | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 12 Participants | 20 Participants | 32 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 16 Participants | 27 Participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Male | 1 Participants | 9 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 21 |
| other Total, other adverse events | 9 / 12 | 16 / 21 |
| serious Total, serious adverse events | 1 / 12 | 2 / 21 |
Outcome results
Primary
Percentage of Participants With Durable Clinically Meaningful Platelet Response of ≥50x10^9/L, for at Least 8 Out of 12 Weeks During the Last 12 Weeks
Percentage of Participants With Durable Clinically Meaningful Platelet Response of ≥50×10\^9/L, for at least 8 out of 12 weeks during the last 12 weeks were reported.
Time frame: During the last 12 weeks (Week 13 to Week 25)
Population: Randomized Set consisted of all enrolled study participants who were randomized. No formal analysis was carried out as the program was terminated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Durable Clinically Meaningful Platelet Response of ≥50x10^9/L, for at Least 8 Out of 12 Weeks During the Last 12 Weeks | 0 Percentage of participants |
| Rozanolixizumab | Percentage of Participants With Durable Clinically Meaningful Platelet Response of ≥50x10^9/L, for at Least 8 Out of 12 Weeks During the Last 12 Weeks | 19.0 Percentage of participants |
Secondary
Change From Baseline to Week 25 in Primary Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) Symptoms Score
The ITP-PAQ Version 1 is a 44 item disease-specific Health-Related Quality of Life questionnaire developed for use in adults with chronic ITP. It includes 10 scales, Four of the scales measure physical health: Symptoms (6 items), Bother (3 items), Fatigue (4 items), and Activity (2 items). Two of the scales measure emotional health: Fear (5 items) and Psychological (5 items) Health. The remaining four scales measure other aspects of quality of life (QOL): Work QOL (4 items), Social QOL (4 items), Women's Reproductive QOL (6 items) and Overall QOL (5 items). Each item is rated on a Likert-type scale containing 4 to 7 responses. All item scores are transformed to a 0 to 100 continuum and are weighted equally to derive individual scale scores and the total score (0-100) is calculated as per the formula: Sum of item scores within the scale/raw sum range\*100. Higher scores indicate better health status.
Time frame: From Baseline during Treatment Period (up to Week 25)
Population: Randomized Set consisted of all enrolled study participants who were randomized. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 25 in Primary Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) Symptoms Score | 6.9 units on a scale | Standard Deviation 13.8 |
| Rozanolixizumab | Change From Baseline to Week 25 in Primary Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) Symptoms Score | 5.5 units on a scale | Standard Deviation 9.2 |
Secondary
Cumulative Number of Weeks With Clinically Meaningful Platelet Response of ≥50×10^9/L Over the 24-week Treatment Period
Total number of weeks with platelet counts ≥50×10\^9/L over the 24-week Treatment Period of the study (Week 1 to Week 25) were reported.
Time frame: Week 1 up to Week 25
Population: Randomized Set consisted of all enrolled study participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Cumulative Number of Weeks With Clinically Meaningful Platelet Response of ≥50×10^9/L Over the 24-week Treatment Period | 0.0 Weeks |
| Rozanolixizumab | Cumulative Number of Weeks With Clinically Meaningful Platelet Response of ≥50×10^9/L Over the 24-week Treatment Period | 3.0 Weeks |
Secondary
Percentage of Participants With Clinically Meaningful Platelet Response of ≥50×10^9/L by Day 8
Clinically meaningful platelet response was defined as platelet count of ≥50×10\^9/L.
Time frame: Baseline to Day 8
Population: Randomized Set consisted of all enrolled study participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Clinically Meaningful Platelet Response of ≥50×10^9/L by Day 8 | 16.7 Percentage of participants |
| Rozanolixizumab | Percentage of Participants With Clinically Meaningful Platelet Response of ≥50×10^9/L by Day 8 | 52.4 Percentage of participants |
Secondary
Percentage of Participants With Response Defined as Platelet Count ≥30*10^9/L and at Least Doubling of Baseline, at Least 2 Separate Occasions at Two Adjacent Nominal Visits at Least 7 Days Apart, and Absence of Bleeding
Response was defined as platelet count ≥30×10\^9/L and at least doubling of baseline, at least 2 separate occasions at two adjacent nominal visits at least 7 days apart, and absence of bleeding.
Time frame: From Baseline during Treatment Period (up to Week 25)
Population: Randomized Set consisted of all enrolled study participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Response Defined as Platelet Count ≥30*10^9/L and at Least Doubling of Baseline, at Least 2 Separate Occasions at Two Adjacent Nominal Visits at Least 7 Days Apart, and Absence of Bleeding | 8.3 Percentage of participants |
| Rozanolixizumab | Percentage of Participants With Response Defined as Platelet Count ≥30*10^9/L and at Least Doubling of Baseline, at Least 2 Separate Occasions at Two Adjacent Nominal Visits at Least 7 Days Apart, and Absence of Bleeding | 33.3 Percentage of participants |
Secondary
Percentage of Participants With TEAEs Leading to Withdrawal of Investigational Medicinal Product (ie, Study Discontinuation)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. TEAEs are defined as AEs starting after the time of first IMP administration up to and including 8 weeks (56 days) after the final dose.
Time frame: From Baseline to end of Safety Follow-Up Period (up to Week 31)
Population: Safety set included all randomized study participants who received at least one dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With TEAEs Leading to Withdrawal of Investigational Medicinal Product (ie, Study Discontinuation) | 0 Percentage of participants |
| Rozanolixizumab | Percentage of Participants With TEAEs Leading to Withdrawal of Investigational Medicinal Product (ie, Study Discontinuation) | 4.8 Percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. TEAEs are defined as AEs starting after the time of first IMP administration up to and including 8 weeks (56 days) after the final dose.
Time frame: From Baseline to end of Safety Follow-Up Period (up to Week 31)
Population: Safety set included all randomized study participants who received at least one dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 75.0 Percentage of participants |
| Rozanolixizumab | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 85.7 Percentage of participants |
Secondary
Time to First Clinically Meaningful Platelet Response (CMPR) of ≥50×10^9/L: Time From Starting Treatment to Achievement of First Response of ≥50×10^9/L
Time from starting treatment to achievement of first Clinically Meaningful Platelet Response of ≥50×10\^9/L was defined as date of first clinically meaningful response - date of first treatment + 1. Median was calculated based upon the Kaplan-Meier estimate.
Time frame: Time from starting treatment to achievement of first response of ≥50×10^9/L (up to Week 25)
Population: Randomized Set consisted of all enrolled study participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Clinically Meaningful Platelet Response (CMPR) of ≥50×10^9/L: Time From Starting Treatment to Achievement of First Response of ≥50×10^9/L | 44.0 days |
| Rozanolixizumab | Time to First Clinically Meaningful Platelet Response (CMPR) of ≥50×10^9/L: Time From Starting Treatment to Achievement of First Response of ≥50×10^9/L | 8.0 days |
Secondary
Time to First Rescue Therapy
Time to first rescue therapy was defined as date of first rescue therapy use - date of first treatment + 1. Median was calculated based upon the Kaplan-Meier estimate. The probability of requiring rescue medication did not reach 0.5 so the KM median in the rozanolixizumab arm could not be estimated.
Time frame: From Baseline to first rescue therapy (up to Week 25)
Population: Randomized Set consisted of all enrolled study participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Rescue Therapy | 34.5 Days |
| Rozanolixizumab | Time to First Rescue Therapy | NA Days |