Primary Immune Thrombocytopenia
Conditions
Keywords
immune thrombocytopenia, sustained platelet count response, bleeding events
Brief summary
This is a randomized, double-blind placebo-controlled multicenter phase 3 trial to evaluate the efficacy and safety of ARGX-113 in participants with primary ITP.
Interventions
BIOLOGICALefgartigimod
Intravenous infusion of efgartigimod
OTHERPlacebo
Intravenous infusion of placebo
Sponsors
argenx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to understand the requirements of the trial, to provide written informed consent (including consent for the use and disclosure of research-related health information), and to comply with the trial protocol procedures (including required trial visits). * Male or female patient aged ≥18 years. * Confirmed ITP diagnosis, at least 3 months before randomization and according to the American Society of Hematology Criteria, and no known other etiology for thrombocytopenia. * Diagnosis supported by a response to a prior ITP therapy (other than thrombopoietin receptor agonists \[TPO-RAs\]), in the opinion of the investigator. * Mean platelet count of \<30×10E9/L from 2 counts: 1 platelet count collected during the screening period and the predose platelet count on the day of randomization. * At the start of the trial, the patient is either on concurrent ITP treatment(s) and has received at least 1 prior therapy for ITP in the past, or the patient is not on treatment for ITP but has received at least 2 prior treatments for ITP. Patients receiving permitted concurrent ITP treatment(s) at baseline, must have been stable in dose and frequency for at least 4 weeks prior to randomization. * Women of childbearing potential must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at baseline before trial medication (infusion) can be administered. * Women of childbearing potential should use a highly effective or acceptable method of contraception during the trial and for 90 days after the last administration of the IMP.
Exclusion criteria
* ITP/thrombocytopenia associated with another condition, eg, lymphoma, chronic lymphocytic leukemia, viral infection, hepatitis, induced or alloimmune thrombocytopenia, or thrombocytopenia associated with myeloid dysplasia. * Use of certain medications before the start of the studies (more details in the protocol) * Patients who have a history of malignancy, including malignant thymoma, or myeloproliferative or lymphoproliferative disorders, unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before screening. Patients with completely excised non-melanoma skin cancer (such as basal cell carcinoma or squamous cell carcinoma) or cervical carcinoma in situ would be permitted at any time. * Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments. * History of any major thrombotic or embolic event within 12 months prior to randomization. * History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia. * History of a recent or planned major surgery (that involves major organs eg, brain, heart, lung, liver, bladder, or gastrointestinal tract) within 4 weeks of randomization. * Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) * Clinical evidence of significant unstable or uncontrolled acute or chronic diseases other than ITPdespite appropriate treatments which could put the patient at undue risk. * Patients with known medical history of hypersensitivity to any of the ingredients of the IMP. * Patients who previously participated in a clinical trial with efgartigimod and have received at least 1 administration of the IMP. * Pregnant or lactating females. More details in the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Chronic ITP With a Sustained Platelet Count Response Defined as Achieving Platelet Counts of at Least 50×10^9/L for at Least 4 of the 6 Visits Between Week 19 and 24 of the Trial. | From Week 19 up to Week 24 | Percentage of participants with chronic ITP with a sustained platelet count response was defined as achieving platelet counts of at least 50 × 10\^9/L for at least 4 of the 6 visits between Week 19 and 24 of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Disease Control Defined as the Number of Cumulative Weeks Over the Planned 24-week Treatment Period With Platelet Counts of ≥50×10^9/L in the Chronic ITP Population | From Week 1 up to Week 24 | Extent of disease control, defined as the cumulative number of weeks over the planned 24-week treatment period with platelet counts of ≥50 × 10\^9/L in the chronic ITP population. |
| Percentage of Participants With a Sustained Platelet Count Response for at Least 4 of the 6 Visits Between Week 19 and 24 of the Study | From Week 19 up to Week 24 | Percentage of participants in the overall population (chronic and persistent ITP) with a sustained platelet count response, defined as achieving platelet counts of at least 50 × 10\^9/L for at least 4 of the 6 visits between weeks 19 and 24 of the study. |
| Incidence and Severity of the WHO-classified Bleeding Events | From Week 1 to Week 24 | Incidence of the World Health Organization (WHO)-classified bleeding events in the overall population. This secondary endpoint used the WHO-classified bleeding scale. Bleeding was the predominant clinical manifestation of ITP and was typically related to platelet count. Accordingly, measuring bleeding was important for monitoring this participant population. |
| Percentage of Participants in the Overall Population Achieving Platelet Counts of at Least 50×10^9/L for at Least 6 of the 8 Visits Between Week 17 and Week 24 | From Week 17 up to Week 24 | Percentage of participants in the overall population achieving platelet counts of at least 50 × 10\^9/L for at least 6 of the 8 visits between Week 17 and 24 of the study. |
Countries
Austria, Belgium, Bulgaria, Czechia, France, Georgia, Germany, Hungary, Italy, Japan, Netherlands, Poland, Russia, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 71 active sites that enrolled participants in 18 countries. Recruitment started on 09 December 2019.
Pre-assignment details
During the screening period (up to 2 weeks) the participant's eligibility for trial participation was evaluated. A total of 205 participants were screened, of which 74 participants were screen failures. 131 of 205 were enrolled and randomized at a ratio of 2:1 to receive efgartigimod or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Efgartigimod Participants receiving efgartigimod
efgartigimod: The participants entered a 24-week treatment period and were randomised to receive efgartigimod 10mg/kg intravenous (IV). The investigational medicinal product (IMP) infusion (efgartigimod) was administered weekly from visits 1 to 4, either weekly or every other week (q2w) from visits 5 to 16, and fixed on the dosing schedule of visit 16 (or the last visit at which IMP was administered) from visits 17 to 24 (ie, either weekly or q2w). | 86 |
| Placebo Participants receiving placebo
Placebo: The participants entered a 24-week treatment period and were randomized to receive placebo intravenous (IV). The placebo infusion was administered weekly from visits 1 to 4, either weekly or q2w from visits 5 to 16, and fixed on the dosing schedule of visit 16 (or the last visit at which placebo was administered) from visits 17 to 24 (ie, either weekly or q2w). | 45 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lack of Efficacy | 8 | 5 |
| Overall Study | Other | 0 | 3 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 3 |
Baseline characteristics
| Characteristic | Efgartigimod | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 13 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 75 Participants | 32 Participants | 107 Participants |
| Age, Continuous | 46.9 years STANDARD_DEVIATION 16.55 | 51.7 years STANDARD_DEVIATION 17.93 | 48.6 years STANDARD_DEVIATION 17.12 |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Japanese | 5 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 77 Participants | 40 Participants | 117 Participants |
| Race/Ethnicity, Customized Unknown or Not reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 80 Participants | 41 Participants | 121 Participants |
| Sex: Female, Male Female | 47 Participants | 24 Participants | 71 Participants |
| Sex: Female, Male Male | 39 Participants | 21 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 86 | 0 / 45 |
| other Total, other adverse events | 80 / 86 | 43 / 45 |
| serious Total, serious adverse events | 7 / 86 | 7 / 45 |
Outcome results
Primary
Percentage of Participants With Chronic ITP With a Sustained Platelet Count Response Defined as Achieving Platelet Counts of at Least 50×10^9/L for at Least 4 of the 6 Visits Between Week 19 and 24 of the Trial.
Percentage of participants with chronic ITP with a sustained platelet count response was defined as achieving platelet counts of at least 50 × 10\^9/L for at least 4 of the 6 visits between Week 19 and 24 of the study.
Time frame: From Week 19 up to Week 24
Population: Full Analysis Set-Chronic population: all randomized participants with chronic ITP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod | Percentage of Participants With Chronic ITP With a Sustained Platelet Count Response Defined as Achieving Platelet Counts of at Least 50×10^9/L for at Least 4 of the 6 Visits Between Week 19 and 24 of the Trial. | 21.8 Percentage of participants |
| Placebo | Percentage of Participants With Chronic ITP With a Sustained Platelet Count Response Defined as Achieving Platelet Counts of at Least 50×10^9/L for at Least 4 of the 6 Visits Between Week 19 and 24 of the Trial. | 5.0 Percentage of participants |
p-value: 0.031695% CI: [1.007, 43.591]Cochran-Mantel-Haenszel
Secondary
Extent of Disease Control Defined as the Number of Cumulative Weeks Over the Planned 24-week Treatment Period With Platelet Counts of ≥50×10^9/L in the Chronic ITP Population
Extent of disease control, defined as the cumulative number of weeks over the planned 24-week treatment period with platelet counts of ≥50 × 10\^9/L in the chronic ITP population.
Time frame: From Week 1 up to Week 24
Population: Full Analysis Set-Chronic population: all randomized participants with chronic ITP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod | Extent of Disease Control Defined as the Number of Cumulative Weeks Over the Planned 24-week Treatment Period With Platelet Counts of ≥50×10^9/L in the Chronic ITP Population | 2.00 Weeks |
| Placebo | Extent of Disease Control Defined as the Number of Cumulative Weeks Over the Planned 24-week Treatment Period With Platelet Counts of ≥50×10^9/L in the Chronic ITP Population | 0.00 Weeks |
p-value: 0.000995% CI: [0, 4]Wilcoxon (Mann-Whitney)
Secondary
Incidence and Severity of the WHO-classified Bleeding Events
Incidence of the World Health Organization (WHO)-classified bleeding events in the overall population. This secondary endpoint used the WHO-classified bleeding scale. Bleeding was the predominant clinical manifestation of ITP and was typically related to platelet count. Accordingly, measuring bleeding was important for monitoring this participant population.
Time frame: From Week 1 to Week 24
Population: Full Analysis Set: all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod | Incidence and Severity of the WHO-classified Bleeding Events | 4.0 bleeding events |
| Placebo | Incidence and Severity of the WHO-classified Bleeding Events | 5.0 bleeding events |
p-value: 0.828795% CI: [0.651, 1.41]Wald Test
Secondary
Percentage of Participants in the Overall Population Achieving Platelet Counts of at Least 50×10^9/L for at Least 6 of the 8 Visits Between Week 17 and Week 24
Percentage of participants in the overall population achieving platelet counts of at least 50 × 10\^9/L for at least 6 of the 8 visits between Week 17 and 24 of the study.
Time frame: From Week 17 up to Week 24
Population: Full Analysis Set: all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod | Percentage of Participants in the Overall Population Achieving Platelet Counts of at Least 50×10^9/L for at Least 6 of the 8 Visits Between Week 17 and Week 24 | 22.1 Percentage of participants |
| Placebo | Percentage of Participants in the Overall Population Achieving Platelet Counts of at Least 50×10^9/L for at Least 6 of the 8 Visits Between Week 17 and Week 24 | 6.7 Percentage of participants |
p-value: 0.026595% CI: [1.048, 22.865]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Sustained Platelet Count Response for at Least 4 of the 6 Visits Between Week 19 and 24 of the Study
Percentage of participants in the overall population (chronic and persistent ITP) with a sustained platelet count response, defined as achieving platelet counts of at least 50 × 10\^9/L for at least 4 of the 6 visits between weeks 19 and 24 of the study.
Time frame: From Week 19 up to Week 24
Population: Full Analysis Set: all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod | Percentage of Participants With a Sustained Platelet Count Response for at Least 4 of the 6 Visits Between Week 19 and 24 of the Study | 25.6 Percentage of participants |
| Placebo | Percentage of Participants With a Sustained Platelet Count Response for at Least 4 of the 6 Visits Between Week 19 and 24 of the Study | 6.7 Percentage of participants |
p-value: 0.010895% CI: [1.268, 26.268]Cochran-Mantel-Haenszel