Primary Immune Thrombocytopenia
Conditions
Brief summary
This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group trial to evaluate the efficacy, safety, and effect on QoL/PRO of efgartigimod PH20 SC treatment in adult patients with primary ITP.
Interventions
BIOLOGICALEfgartigimod PH20 SC
Subcutaneous injection with efgartigimod PH20 SC
OTHERPlacebo PH20 SC
Subcutaneous injection with placebo PH20 SC
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 and provide written informed consent, willing and able to comply with the trial protocol procedures * Is at least the local age of consent for clinical studies when signing the ICF. * Confirmed diagnosis of primary ITP made at least 3 months before randomization and based on the American Society of Hematology Criteria, and no known etiology for thrombocytopenia * Diagnosis supported by a response to a prior ITP therapy (other than TPO-RAs), in the opinion of the investigator * Mean platelet count of \<30×10E9/L from at least 3 documented, qualifying counts within the 3 preceding months where at least 2 of the qualifying counts must be taken during the screening period: 1 platelet count collected during the screening period and the predose platelet count on the day of randomization (visit 1). If the third count is not available from the 3 preceding months, this third platelet count can be obtained during the screening period. * A documented history of a platelet count of \<30×10E9/L before screening * At the start of the trial, the participant either takes concurrent ITP treatment(s) and has received at least 1 prior therapy for ITP in the past, or the participant does not take treatment for ITP (see note) but has received at least 2 prior treatments for ITP. Participants receiving permitted concurrent ITP treatment(s) at baseline must have been stable in dose and frequency for at least 4 weeks before randomization. Permitted concurrent ITP medications include corticosteroids, danazol, vinca alkaloids, oral immunosuppressants, dapsone, fostamatinib, and/or oral TPO-RAs. -Agree to use contraceptive measures consistent with local regulations and the protocol
Exclusion criteria
* Secondary ITP/thrombocytopenia associated with another condition, eg, lymphoma, chronic lymphocytic leukemia, viral infection, hepatitis, induced or alloimmune thrombocytopenia, thrombocytopenia associated with myeloid dysplasia, or hematopoietic stem cell transplant * Use of anticoagulants (eg, vitamin K antagonists, direct oral anticoagulants) within 4 weeks prior to randomization * Use of any transfusions within 4 weeks prior to randomization * Use of Ig (IV, SC, or intramuscular route) or plasmapheresis (PLEX) within 4 weeks prior to randomization * Use of romiplostim within 4 weeks prior to randomization * Undergone splenectomy less than 4 weeks prior to randomization * Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP * Use of any monoclonal antibody or Fc fusion proteins, other than those previously indicated, within 6 months before the first dose of the IMP (eg, anti-CD20) * At the screening visit, clinically significant laboratory abnormalities as follows: Hemoglobin ≤9 g/dL - OR - International normalized ratio \>1.5 or activated partial thromboplastin time \>1.5×upper limit of normal - OR - total IgG level \<6 g/L * History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of IMP. Participants with the following cancer can be included at any time: Adequately treated basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast or Incidental histological finding of prostate cancer (TNM stage T1a or T1b) * 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 (eg, myocardial infarction, stroke, deep venous thrombosis, or pulmonary embolism) within 5 years prior to randomization * History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia * Evidence of an active clinically significant bleeding of an organ or internal mucosal bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic procedure based on the investigator's judgment (eg, intracranial hemorrhage, pulmonary hemorrhage, bleeding with ongoing need for packed red blood cell transfusion) * Estimated high risk of a clinically significant bleeding of an organ or internal mucosal bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic procedure according to the investigator's judgment * Clinical evidence of other significant serious diseases, have had a recent major surgery, or who have any other condition in the opinion of the investigator, that could confound the results of the trial or put the participant at undue risk * Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B virus (HBV) that is indicative of an acute or chronic infection, unless associated with a negative HBV DNA test, Hepatitis C virus (HCV) based on HCV-antibody assay (unless associated with a negative HCV RNA test), Human immunodeficiency virus (HIV) based on test results that are associated with an acquired immunodeficiency syndrome (AIDS)-defining condition or a CD4 count ≤200 cells/mm3 * Known hypersensitivity reaction to efgartigimod, rHuPH20, or 1 of its excipients * Previously participated in a clinical trial with efgartigimod and have received at least 1 administration of the IMP * Pregnant or lactating or intends to become pregnant during the trial * Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening * Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of ITP or put the participant at undue risk * Clinical evidence of significant unstable or uncontrolled acute or chronic diseases other than ITP (eg, cardiovascular, pulmonary, hematologic, gastrointestinal, endocrine, hepatic, renal, neurological, malignancy, infectious diseases, uncontrolled diabetes) despite appropriate treatments which could put the participant at undue risk * Current or history of (ie, within 12 months of screening) alcohol, drug, or medication abuse * Received a live/live-attenuated vaccine less than 4 weeks before screening. The receipt of any inactivated, sub-unit, polysaccharide, or conjugate vaccine at any time before screening is not considered an exclusion criterion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Chronic Immune Thrombocytopenia (ITP) With a Sustained Platelet Count Response Between Weeks 19 and 24 | Up to 6 weeks (between Weeks 19 and 24) | A participant was considered a responder for this endpoint (i.e., had a sustained platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥4 of the 6 analysis visits between Weeks 19 and 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in the Overall Population (Chronic and Persistent ITP) With a Sustained Platelet Count Response Between Weeks 19 and 24 | Up to 6 weeks (between Weeks 19 and 24) | A participant was considered a responder for this endpoint (i.e., had a sustained platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥4 of the 6 analysis visits between Weeks 19 and 24. |
| Percentage of Participants in the Overall Population With Sustained Platelet Count Response Between Weeks 17 and 24 | Up to 8 weeks (between Weeks 17 and 24) | A participant was considered a responder for this endpoint (i.e., had a sustained platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥6 of the 8 analysis visits between weeks 17 and 24. |
| Percentage of Participants in the Overall Population Achieving Overall Platelet Count Response at Any Time During the 24-week Treatment Period | Up to 24 weeks | A participant was considered a responder for this endpoint (i.e., had an overall platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥4 analysis visits at any time during the 24-week treatment period. |
| Extent of Disease Control Until Week 12 in the Overall Population | Up to 12 weeks | Extent of disease control was defined as the number of cumulative weeks until Week 12 with platelet counts of ≥50×10\^9/L in the overall population. |
| Percentage of Participants in the Overall Population Achieving Overall Platelet Count Response at Any Time Until Week 12 | Up to 12 weeks | A participant was considered a responder for this endpoint (i.e., had an overall platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥4 analysis visits at any time until Week 12. |
| Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, Safety and Efficacy Follow-up Visit 1 (SEFU1) (up to Week 29), and SEFU2 (up to Week 33) | Change from Baseline at time point t = value at time point t - Baseline value. Baseline was defined as the last available value prior to first administration of the investigational medicinal product (IMP). |
| Time to Platelet Count Response in the Overall Population | Up to 24 weeks | Time to platelet count response, defined as the time to have 2 consecutive platelet counts of ≥50 × 10\^9/L via Kaplan-Meier estimates. |
| Extent of Disease Control Over the 24-Week Treatment Period in the Overall Population | Up to 24 weeks | Extent of disease control was defined as the number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥30×10\^9/L with at least ≥20×10\^9/L above Baseline in the overall population. |
| Extent of Disease Control Over the 24-Week Treatment Period in the Overall Population for Participants With Baseline Platelet Count of <15×10^9/L | Up to 24 weeks | Extent of disease control was defined as the number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥30×10\^9/L with at least ≥20×10\^9/L above Baseline in the overall population. |
| Number of the World Health Organization (WHO)-Classified Bleeding Events (Grade ≥1) in the Overall Population | Up to 24 weeks | Assessed using the WHO bleeding scale. The WHO bleeding scale is a five-point scale where Grade 0 = no bleeding; Grade 1 = petechial bleeding; Grade 2 = mild blood loss; Grade 3 = gross blood loss (requires transfusion); and Grade 4 = debilitating blood loss, associated with fatality. |
| Percentage of Participants With a Platelet Count International Working Group (IWG) Response | Up to 24 weeks | IWG complete response was defined as platelet counts of ≥100 × 10\^9/L and the absence of bleeding events (WHO Grading = 0 \[no bleeding\]) for at least 2 separate, consecutive analysis visits at least 7 days apart. IWG response was defined as platelet counts of ≥30 × 10\^9/L and a 2-fold increase of platelet count from Baseline and the absence of bleeding events (WHO grading = 0) for at least 2 separate, consecutive analysis visits that were at least 7 days apart. Initial response was defined as platelet counts of ≥30 × 10\^9/L and a 2-fold increase from the Baseline platelet count at analysis visit 5. |
| Extent of Disease Control Over the 24-Week Treatment Period in the Chronic ITP Population | Up to 24 weeks | Extent of disease control was 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. |
| Percentage of Participants for Whom Dose and/or Frequency of Concurrent ITP Therapies Have Increased at Week 12 or Later in the Overall Population | Up to 13 weeks (between Weeks 12 and 24) | A change in ITP therapy was defined as either an increase in the dose and/or frequency of a concurrent ITP therapy relative to Baseline or the initiation of a new concurrent ITP therapy. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 24 in the Overall Population | Baseline and Week 24 | The FACIT-fatigue scale is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during his/her usual daily activities over the past week. The level of fatigue was measured by recording item responses on a 5-point Likert scale ranging from 0 not at all to 4 very much. All items were summed to create a single fatigue score with a range from 0 to 52, where a higher FACIT-F score indicated more severe symptoms. A negative change score from Baseline indicated improvement in quality of life (QoL). |
| Change From Baseline in Functional Assessment of Cancer Therapy Questionnaire-Th6 (Fact-Th6) at Week 24 in the Overall Population | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | The FACT-Th6 uses a 5-level Likert scale (0=not at all to 4=very much), with participants rating their degree of concern in the past 7 days. The 6 selected items pertain to ability to do usual activities, worry about problems with bleeding or bruising, worry about the possibility of serious bleeding, avoidance of physical or social activity because of concern with bleeding or bruising and frustration due to the inability to carry out usual activities. All items were summed to create a single score with a range from 0 to 24, where a higher score indicated less severe symptoms. A positive change score from Baseline indicated improvement in QoL. |
| Change From Baseline in Short Form-36 (SF-36) at Week 24 in the Overall Population | Baseline and Week 24 | The SF-36 is a 36-item scale constructed to survey health-related QoL on 8 domains: limitations in physical activities due to health problems; limitations in social activities due to physical or emotional problems; limitations in usual role activities due to physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities due to emotional problems; vitality (energy and fatigue); and general health perceptions. The scores from the 8 domains were evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The summary component scores could range from 0 to 100, where a higher score indicated improvement in QoL. A positive change score from Baseline indicated improvement in QoL. |
| Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Up to 35 weeks | Anti-drug antibody (ADA) incidence was defined as the percentage of participants with treatment-induced or treatment boosted ADA (denominator: number of evaluable participants). ADA prevalence was defined as the percentage of participants with treatment-unaffected ADA, treatment-induced ADA or treatment-boosted ADA (denominator: number of evaluable participants). |
| Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Weeks 3, 7, 11, 15, 19, 23, 24, SEFU1 (up to Week 29), and SEFU2 (up to Week 33) | A titer was determined in the samples with a positive assay response. |
| Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population | Up to 35 weeks | Samples were tested for the presence of NAb against efgartigimod and/or rHuPH20 and titers for NAb against rHuPH20. NAb incidence is defined as the total percentage of participants with participant classification baseline negative-postbaseline positive and baseline positive-postbaseline positive. NAb prevalence is defined as the total percentage of participants with participant classification baseline negative-postbaseline positive, baseline positive-postbaseline positive, or baseline positive-postbaseline negative. |
| Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population | Predose on Weeks 1, 2, 3, 17, 19, 21, 23, and 24 | All pharmacokinetic (PK) samples were collected predose, on the day of IMP administration. |
| Percentage Change From Baseline in Total IgG in the Overall Population | Baseline and Weeks 1, 2, 3, 17, 19, 21, 23, and 24 | Samples were collected predose, on the day of IMP administration. |
| Number of Participants With Antiplatelet Antibodies in the Overall Population | Weeks 7, 15, 23, and 24 | The antiplatelet antibody was positive if optical density value \>0.129. |
| Rate of Receipt of Rescue Therapy (Rescue Per Participant Per Month) in the Overall Population | Up to 24 weeks | Rescue therapy was defined as an occurrence where the participant needed treatment with 1 or more rescue treatments. An occurrence was defined as a period of maximum 5 days where 1 or more rescue treatments were administered simultaneously or consecutively to the trial participant. The following rescue treatments were permitted: methylprednisolone, dexamethasone, prednisone, normal immunoglobulins, anti-D (Rho) immunoglobins, or platelet transfusions. |
Countries
Argentina, Australia, Bulgaria, Chile, China, Denmark, France, Georgia, Germany, Greece, Ireland, Israel, Italy, Japan, Jordan, Mexico, New Zealand, Norway, Poland, Portugal, Romania, Russia, Serbia, South Africa, South Korea, Spain, Taiwan, Thailand, Tunisia, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A regionally diverse participant population was enrolled (including but not limited to North America, East Asia, Europe, and the rest of world \[ROW\]). A total of 207 participants were randomized to IMP: 137 participants in the efgartigimod PH20 subcutaneous (SC) arm and 70 participants in the placebo PH20 SC arm.
Participants by arm
| Arm | Count |
|---|---|
| Efgartigimod PH20 SC Participants receiving efgartigimod PH20 SC treatment. | 137 |
| Placebo PH20 SC Participants receiving placebo PH20 SC treatment. | 70 |
| Total | 207 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Miscellaneous | 4 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Requires Prohibited Medication | 2 | 0 |
| Overall Study | Withdrawal of Consent | 11 | 6 |
Baseline characteristics
| Characteristic | Efgartigimod PH20 SC | Placebo PH20 SC | Total |
|---|---|---|---|
| Age, Continuous | 47.3 years STANDARD_DEVIATION 17.22 | 50.0 years STANDARD_DEVIATION 15.29 | 48.2 years STANDARD_DEVIATION 16.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 129 Participants | 68 Participants | 197 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 44 Participants | 18 Participants | 62 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 88 Participants | 49 Participants | 137 Participants |
| Sex: Female, Male Female | 88 Participants | 43 Participants | 131 Participants |
| Sex: Female, Male Male | 49 Participants | 27 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 137 | 0 / 70 |
| other Total, other adverse events | 130 / 137 | 65 / 70 |
| serious Total, serious adverse events | 14 / 137 | 10 / 70 |
Outcome results
Primary
Percentage of Participants With Chronic Immune Thrombocytopenia (ITP) With a Sustained Platelet Count Response Between Weeks 19 and 24
A participant was considered a responder for this endpoint (i.e., had a sustained platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥4 of the 6 analysis visits between Weeks 19 and 24.
Time frame: Up to 6 weeks (between Weeks 19 and 24)
Population: Full Analysis Set (FAS)-Chronic: Participants from the FAS (all randomized participants) including only participants with chronic ITP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | Percentage of Participants With Chronic Immune Thrombocytopenia (ITP) With a Sustained Platelet Count Response Between Weeks 19 and 24 | 13.7 percentage of participants |
| Placebo PH20 SC | Percentage of Participants With Chronic Immune Thrombocytopenia (ITP) With a Sustained Platelet Count Response Between Weeks 19 and 24 | 16.2 percentage of participants |
p-value: 0.508195% CI: [-14.7, 7]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy Questionnaire-Th6 (Fact-Th6) at Week 24 in the Overall Population
The FACT-Th6 uses a 5-level Likert scale (0=not at all to 4=very much), with participants rating their degree of concern in the past 7 days. The 6 selected items pertain to ability to do usual activities, worry about problems with bleeding or bruising, worry about the possibility of serious bleeding, avoidance of physical or social activity because of concern with bleeding or bruising and frustration due to the inability to carry out usual activities. All items were summed to create a single score with a range from 0 to 24, where a higher score indicated less severe symptoms. A positive change score from Baseline indicated improvement in QoL.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Population: FAS: All randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Efgartigimod PH20 SC | Change From Baseline in Functional Assessment of Cancer Therapy Questionnaire-Th6 (Fact-Th6) at Week 24 in the Overall Population | 0.225 score on a scale | Standard Error 0.36 |
| Placebo PH20 SC | Change From Baseline in Functional Assessment of Cancer Therapy Questionnaire-Th6 (Fact-Th6) at Week 24 in the Overall Population | 0.359 score on a scale | Standard Error 0.498 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 24 in the Overall Population
The FACIT-fatigue scale is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during his/her usual daily activities over the past week. The level of fatigue was measured by recording item responses on a 5-point Likert scale ranging from 0 not at all to 4 very much. All items were summed to create a single fatigue score with a range from 0 to 52, where a higher FACIT-F score indicated more severe symptoms. A negative change score from Baseline indicated improvement in quality of life (QoL).
Time frame: Baseline and Week 24
Population: FAS: All randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Efgartigimod PH20 SC | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 24 in the Overall Population | -0.025 score on a scale | Standard Error 0.712 |
| Placebo PH20 SC | Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) at Week 24 in the Overall Population | 0.741 score on a scale | Standard Error 0.985 |
Secondary
Change From Baseline in Short Form-36 (SF-36) at Week 24 in the Overall Population
The SF-36 is a 36-item scale constructed to survey health-related QoL on 8 domains: limitations in physical activities due to health problems; limitations in social activities due to physical or emotional problems; limitations in usual role activities due to physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities due to emotional problems; vitality (energy and fatigue); and general health perceptions. The scores from the 8 domains were evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The summary component scores could range from 0 to 100, where a higher score indicated improvement in QoL. A positive change score from Baseline indicated improvement in QoL.
Time frame: Baseline and Week 24
Population: FAS: All randomized participants.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Change From Baseline in Short Form-36 (SF-36) at Week 24 in the Overall Population | Week 24: Mental Component | 1.215 score on a scale | Standard Error 0.62 |
| Efgartigimod PH20 SC | Change From Baseline in Short Form-36 (SF-36) at Week 24 in the Overall Population | Week 24: Physical Component | -0.848 score on a scale | Standard Error 0.525 |
| Placebo PH20 SC | Change From Baseline in Short Form-36 (SF-36) at Week 24 in the Overall Population | Week 24: Mental Component | 0.957 score on a scale | Standard Error 0.841 |
| Placebo PH20 SC | Change From Baseline in Short Form-36 (SF-36) at Week 24 in the Overall Population | Week 24: Physical Component | -0.850 score on a scale | Standard Error 0.712 |
Secondary
Extent of Disease Control Over the 24-Week Treatment Period in the Chronic ITP Population
Extent of disease control was 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.
Time frame: Up to 24 weeks
Population: FAS-Chronic: Participants from the FAS (all randomized participants) including only participants with chronic ITP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod PH20 SC | Extent of Disease Control Over the 24-Week Treatment Period in the Chronic ITP Population | 0.5 weeks |
| Placebo PH20 SC | Extent of Disease Control Over the 24-Week Treatment Period in the Chronic ITP Population | 0.0 weeks |
p-value: 0.492595% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Extent of Disease Control Over the 24-Week Treatment Period in the Overall Population
Extent of disease control was defined as the number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥30×10\^9/L with at least ≥20×10\^9/L above Baseline in the overall population.
Time frame: Up to 24 weeks
Population: FAS: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod PH20 SC | Extent of Disease Control Over the 24-Week Treatment Period in the Overall Population | 1.0 weeks |
| Placebo PH20 SC | Extent of Disease Control Over the 24-Week Treatment Period in the Overall Population | 1.0 weeks |
p-value: 0.292995% CI: [0, 1]Wilcoxon (Mann-Whitney)
Secondary
Extent of Disease Control Over the 24-Week Treatment Period in the Overall Population for Participants With Baseline Platelet Count of <15×10^9/L
Extent of disease control was defined as the number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥30×10\^9/L with at least ≥20×10\^9/L above Baseline in the overall population.
Time frame: Up to 24 weeks
Population: FAS: All randomized participants with Baseline Platelet Count of \<15×10\^9/L.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod PH20 SC | Extent of Disease Control Over the 24-Week Treatment Period in the Overall Population for Participants With Baseline Platelet Count of <15×10^9/L | 1.0 weeks |
| Placebo PH20 SC | Extent of Disease Control Over the 24-Week Treatment Period in the Overall Population for Participants With Baseline Platelet Count of <15×10^9/L | 0.0 weeks |
p-value: 0.147595% CI: [0, 1]Wilcoxon (Mann-Whitney)
Secondary
Extent of Disease Control Until Week 12 in the Overall Population
Extent of disease control was defined as the number of cumulative weeks until Week 12 with platelet counts of ≥50×10\^9/L in the overall population.
Time frame: Up to 12 weeks
Population: FAS: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod PH20 SC | Extent of Disease Control Until Week 12 in the Overall Population | 0.00 weeks |
| Placebo PH20 SC | Extent of Disease Control Until Week 12 in the Overall Population | 0.00 weeks |
p-value: 0.72695% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population
Anti-drug antibody (ADA) incidence was defined as the percentage of participants with treatment-induced or treatment boosted ADA (denominator: number of evaluable participants). ADA prevalence was defined as the percentage of participants with treatment-unaffected ADA, treatment-induced ADA or treatment-boosted ADA (denominator: number of evaluable participants).
Time frame: Up to 35 weeks
Population: SAF: All participants who received at least 1 dose or part of a dose including only antibody-evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Efgartigimod PH20 SC | Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Incidence of Antibodies to Efgartigimod | 5.1 percentage of participants |
| Efgartigimod PH20 SC | Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Prevalence of Antibodies to Efgartigimod | 16.2 percentage of participants |
| Efgartigimod PH20 SC | Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Incidence of Antibodies to rHuPH20 | 41.2 percentage of participants |
| Efgartigimod PH20 SC | Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Prevalence of Antibodies to rHuPH20 | 50.0 percentage of participants |
| Placebo PH20 SC | Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Prevalence of Antibodies to rHuPH20 | 31.4 percentage of participants |
| Placebo PH20 SC | Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Incidence of Antibodies to Efgartigimod | 2.9 percentage of participants |
| Placebo PH20 SC | Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Incidence of Antibodies to rHuPH20 | 20.0 percentage of participants |
| Placebo PH20 SC | Incidence and Prevalence of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Prevalence of Antibodies to Efgartigimod | 7.1 percentage of participants |
Secondary
Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population
Samples were tested for the presence of NAb against efgartigimod and/or rHuPH20 and titers for NAb against rHuPH20. NAb incidence is defined as the total percentage of participants with participant classification baseline negative-postbaseline positive and baseline positive-postbaseline positive. NAb prevalence is defined as the total percentage of participants with participant classification baseline negative-postbaseline positive, baseline positive-postbaseline positive, or baseline positive-postbaseline negative.
Time frame: Up to 35 weeks
Population: SAF: All participants who received at least 1 dose or part of a dose with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Efgartigimod PH20 SC | Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population | Incidence of NAb to Efgartigimod | 0.7 percentage of participants |
| Efgartigimod PH20 SC | Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population | Prevalence of NAb to Efgartigimod | 5.1 percentage of participants |
| Efgartigimod PH20 SC | Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population | Incidence of NAb to rHuPH20 | 0.0 percentage of participants |
| Efgartigimod PH20 SC | Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population | Prevalence of NAb to rHuPH20 | 0.0 percentage of participants |
| Placebo PH20 SC | Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population | Prevalence of NAb to rHuPH20 | 0.0 percentage of participants |
| Placebo PH20 SC | Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population | Incidence of NAb to Efgartigimod | 0.0 percentage of participants |
| Placebo PH20 SC | Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population | Incidence of NAb to rHuPH20 | 0.0 percentage of participants |
| Placebo PH20 SC | Incidence and Prevalence of Neutralizing Antibodies (NAb) to Efgartigimod and/or rHuPH20 in the Overall Population | Prevalence of NAb to Efgartigimod | 0.0 percentage of participants |
Secondary
Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population
Change from Baseline at time point t = value at time point t - Baseline value. Baseline was defined as the last available value prior to first administration of the investigational medicinal product (IMP).
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, Safety and Efficacy Follow-up Visit 1 (SEFU1) (up to Week 29), and SEFU2 (up to Week 33)
Population: FAS: All randomized participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 3 | 17.07 platelets x10^9/L | Standard Deviation 39.855 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 14 | 23.60 platelets x10^9/L | Standard Deviation 47.521 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 8 | 21.77 platelets x10^9/L | Standard Deviation 52.308 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 15 | 21.30 platelets x10^9/L | Standard Deviation 45.776 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 5 | 18.14 platelets x10^9/L | Standard Deviation 54.335 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 16 | 30.32 platelets x10^9/L | Standard Deviation 71.553 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 9 | 19.90 platelets x10^9/L | Standard Deviation 54.542 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 17 | 25.12 platelets x10^9/L | Standard Deviation 54.747 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 2 | 16.62 platelets x10^9/L | Standard Deviation 49.408 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 18 | 28.54 platelets x10^9/L | Standard Deviation 53.115 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 10 | 21.73 platelets x10^9/L | Standard Deviation 47.685 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 19 | 33.86 platelets x10^9/L | Standard Deviation 59.323 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 6 | 34.61 platelets x10^9/L | Standard Deviation 112.204 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 20 | 30.87 platelets x10^9/L | Standard Deviation 55.342 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 11 | 20.13 platelets x10^9/L | Standard Deviation 42.193 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 21 | 30.04 platelets x10^9/L | Standard Deviation 61.438 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 22 | 33.26 platelets x10^9/L | Standard Deviation 61.558 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 4 | 12.39 platelets x10^9/L | Standard Deviation 37.886 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 23 | 29.51 platelets x10^9/L | Standard Deviation 53.437 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 12 | 21.02 platelets x10^9/L | Standard Deviation 43.882 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 24 | 25.51 platelets x10^9/L | Standard Deviation 52.203 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 7 | 28.25 platelets x10^9/L | Standard Deviation 107.932 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | SEFU1 | 40.44 platelets x10^9/L | Standard Deviation 64.86 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 13 | 22.29 platelets x10^9/L | Standard Deviation 44.654 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | SEFU2 | 30.00 platelets x10^9/L | Standard Deviation 35.011 |
| Efgartigimod PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 1 | 13.84 platelets x10^9/L | Standard Deviation 41.15 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | SEFU2 | 56.25 platelets x10^9/L | Standard Deviation 85.206 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 1 | 8.82 platelets x10^9/L | Standard Deviation 34.355 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 2 | 23.54 platelets x10^9/L | Standard Deviation 85.005 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 3 | 19.22 platelets x10^9/L | Standard Deviation 71.947 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 4 | 9.31 platelets x10^9/L | Standard Deviation 26.813 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 5 | 12.24 platelets x10^9/L | Standard Deviation 30.059 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 6 | 16.35 platelets x10^9/L | Standard Deviation 40.891 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 7 | 13.46 platelets x10^9/L | Standard Deviation 41.876 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 8 | 16.57 platelets x10^9/L | Standard Deviation 42.508 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 9 | 20.42 platelets x10^9/L | Standard Deviation 53.488 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 10 | 15.42 platelets x10^9/L | Standard Deviation 33.119 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 11 | 14.54 platelets x10^9/L | Standard Deviation 25.588 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 12 | 22.28 platelets x10^9/L | Standard Deviation 56.173 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 13 | 15.51 platelets x10^9/L | Standard Deviation 37.651 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 14 | 24.04 platelets x10^9/L | Standard Deviation 55.678 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 15 | 28.05 platelets x10^9/L | Standard Deviation 67.897 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 16 | 23.09 platelets x10^9/L | Standard Deviation 46.154 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 17 | 30.05 platelets x10^9/L | Standard Deviation 56.581 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 18 | 31.64 platelets x10^9/L | Standard Deviation 57.309 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 19 | 37.26 platelets x10^9/L | Standard Deviation 68.832 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 20 | 25.85 platelets x10^9/L | Standard Deviation 48.409 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 21 | 26.23 platelets x10^9/L | Standard Deviation 50.323 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 22 | 29.23 platelets x10^9/L | Standard Deviation 55.175 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 23 | 24.89 platelets x10^9/L | Standard Deviation 41.103 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | Week 24 | 24.91 platelets x10^9/L | Standard Deviation 42.972 |
| Placebo PH20 SC | Mean Change From Baseline in Platelet Count at Each Visit in the Overall Population | SEFU1 | 48.70 platelets x10^9/L | — |
Secondary
Number of Participants With Antiplatelet Antibodies in the Overall Population
The antiplatelet antibody was positive if optical density value \>0.129.
Time frame: Weeks 7, 15, 23, and 24
Population: PD Analysis Set: Safety analysis set including participants with at least one serum post dose PD measurement and tested positive for antiplatelet antibodies at Baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Efgartigimod PH20 SC | Number of Participants With Antiplatelet Antibodies in the Overall Population | Week 7 | 20 Participants |
| Efgartigimod PH20 SC | Number of Participants With Antiplatelet Antibodies in the Overall Population | Week 15 | 18 Participants |
| Efgartigimod PH20 SC | Number of Participants With Antiplatelet Antibodies in the Overall Population | Week 23 | 17 Participants |
| Efgartigimod PH20 SC | Number of Participants With Antiplatelet Antibodies in the Overall Population | Week 24 | 19 Participants |
| Placebo PH20 SC | Number of Participants With Antiplatelet Antibodies in the Overall Population | Week 24 | 8 Participants |
| Placebo PH20 SC | Number of Participants With Antiplatelet Antibodies in the Overall Population | Week 7 | 10 Participants |
| Placebo PH20 SC | Number of Participants With Antiplatelet Antibodies in the Overall Population | Week 23 | 9 Participants |
| Placebo PH20 SC | Number of Participants With Antiplatelet Antibodies in the Overall Population | Week 15 | 10 Participants |
Secondary
Number of the World Health Organization (WHO)-Classified Bleeding Events (Grade ≥1) in the Overall Population
Assessed using the WHO bleeding scale. The WHO bleeding scale is a five-point scale where Grade 0 = no bleeding; Grade 1 = petechial bleeding; Grade 2 = mild blood loss; Grade 3 = gross blood loss (requires transfusion); and Grade 4 = debilitating blood loss, associated with fatality.
Time frame: Up to 24 weeks
Population: FAS: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod PH20 SC | Number of the World Health Organization (WHO)-Classified Bleeding Events (Grade ≥1) in the Overall Population | 9.0 bleeding events |
| Placebo PH20 SC | Number of the World Health Organization (WHO)-Classified Bleeding Events (Grade ≥1) in the Overall Population | 10.0 bleeding events |
Comparison: WHO Classified Bleeding Event Grade ≥1p-value: 0.767795% CI: [-2, 2]Wilcoxon (Mann-Whitney)
Secondary
Percentage Change From Baseline in Total IgG in the Overall Population
Samples were collected predose, on the day of IMP administration.
Time frame: Baseline and Weeks 1, 2, 3, 17, 19, 21, 23, and 24
Population: Pharmacodynamic (PD) Analysis Set: Safety analysis set including participants with at least one serum post dose PD measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 17 | -64.76 percentage of total IgG | Standard Deviation 11.478 |
| Efgartigimod PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 2 | -50.68 percentage of total IgG | Standard Deviation 34.973 |
| Efgartigimod PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 19 | -60.98 percentage of total IgG | Standard Deviation 26.46 |
| Efgartigimod PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 1 | -33.64 percentage of total IgG | Standard Deviation 26.018 |
| Efgartigimod PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 23 | -62.45 percentage of total IgG | Standard Deviation 20.286 |
| Efgartigimod PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 3 | -56.80 percentage of total IgG | Standard Deviation 39.133 |
| Efgartigimod PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 24 | -61.97 percentage of total IgG | Standard Deviation 18.2 |
| Efgartigimod PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 21 | -62.38 percentage of total IgG | Standard Deviation 15.176 |
| Placebo PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 24 | -0.36 percentage of total IgG | Standard Deviation 17.408 |
| Placebo PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 1 | 0.60 percentage of total IgG | Standard Deviation 14.065 |
| Placebo PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 2 | 10.31 percentage of total IgG | Standard Deviation 44.858 |
| Placebo PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 3 | 4.97 percentage of total IgG | Standard Deviation 28.484 |
| Placebo PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 17 | 1.27 percentage of total IgG | Standard Deviation 16.749 |
| Placebo PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 21 | 4.62 percentage of total IgG | Standard Deviation 25.406 |
| Placebo PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 23 | 2.45 percentage of total IgG | Standard Deviation 21.271 |
| Placebo PH20 SC | Percentage Change From Baseline in Total IgG in the Overall Population | Week 19 | 9.28 percentage of total IgG | Standard Deviation 44.989 |
Secondary
Percentage of Participants for Whom Dose and/or Frequency of Concurrent ITP Therapies Have Increased at Week 12 or Later in the Overall Population
A change in ITP therapy was defined as either an increase in the dose and/or frequency of a concurrent ITP therapy relative to Baseline or the initiation of a new concurrent ITP therapy.
Time frame: Up to 13 weeks (between Weeks 12 and 24)
Population: FAS: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | Percentage of Participants for Whom Dose and/or Frequency of Concurrent ITP Therapies Have Increased at Week 12 or Later in the Overall Population | 11.7 percentage of participants |
| Placebo PH20 SC | Percentage of Participants for Whom Dose and/or Frequency of Concurrent ITP Therapies Have Increased at Week 12 or Later in the Overall Population | 15.7 percentage of participants |
95% CI: [-15.6, 5.7]
Secondary
Percentage of Participants in the Overall Population Achieving Overall Platelet Count Response at Any Time During the 24-week Treatment Period
A participant was considered a responder for this endpoint (i.e., had an overall platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥4 analysis visits at any time during the 24-week treatment period.
Time frame: Up to 24 weeks
Population: FAS: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | Percentage of Participants in the Overall Population Achieving Overall Platelet Count Response at Any Time During the 24-week Treatment Period | 29.9 percentage of participants |
| Placebo PH20 SC | Percentage of Participants in the Overall Population Achieving Overall Platelet Count Response at Any Time During the 24-week Treatment Period | 25.7 percentage of participants |
95% CI: [-9.3, 16.8]
Secondary
Percentage of Participants in the Overall Population Achieving Overall Platelet Count Response at Any Time Until Week 12
A participant was considered a responder for this endpoint (i.e., had an overall platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥4 analysis visits at any time until Week 12.
Time frame: Up to 12 weeks
Population: FAS: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | Percentage of Participants in the Overall Population Achieving Overall Platelet Count Response at Any Time Until Week 12 | 18.2 percentage of participants |
| Placebo PH20 SC | Percentage of Participants in the Overall Population Achieving Overall Platelet Count Response at Any Time Until Week 12 | 15.7 percentage of participants |
95% CI: [-9.6, 13]
Secondary
Percentage of Participants in the Overall Population (Chronic and Persistent ITP) With a Sustained Platelet Count Response Between Weeks 19 and 24
A participant was considered a responder for this endpoint (i.e., had a sustained platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥4 of the 6 analysis visits between Weeks 19 and 24.
Time frame: Up to 6 weeks (between Weeks 19 and 24)
Population: FAS: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | Percentage of Participants in the Overall Population (Chronic and Persistent ITP) With a Sustained Platelet Count Response Between Weeks 19 and 24 | 16.1 percentage of participants |
| Placebo PH20 SC | Percentage of Participants in the Overall Population (Chronic and Persistent ITP) With a Sustained Platelet Count Response Between Weeks 19 and 24 | 15.7 percentage of participants |
p-value: 0.931495% CI: [-11.7, 10]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in the Overall Population With Sustained Platelet Count Response Between Weeks 17 and 24
A participant was considered a responder for this endpoint (i.e., had a sustained platelet count response) if the participant had platelet counts of ≥50 × 10\^9/L for ≥6 of the 8 analysis visits between weeks 17 and 24.
Time frame: Up to 8 weeks (between Weeks 17 and 24)
Population: FAS: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efgartigimod PH20 SC | Percentage of Participants in the Overall Population With Sustained Platelet Count Response Between Weeks 17 and 24 | 12.4 percentage of participants |
| Placebo PH20 SC | Percentage of Participants in the Overall Population With Sustained Platelet Count Response Between Weeks 17 and 24 | 14.3 percentage of participants |
p-value: 0.737995% CI: [-12.4, 8.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Platelet Count International Working Group (IWG) Response
IWG complete response was defined as platelet counts of ≥100 × 10\^9/L and the absence of bleeding events (WHO Grading = 0 \[no bleeding\]) for at least 2 separate, consecutive analysis visits at least 7 days apart. IWG response was defined as platelet counts of ≥30 × 10\^9/L and a 2-fold increase of platelet count from Baseline and the absence of bleeding events (WHO grading = 0) for at least 2 separate, consecutive analysis visits that were at least 7 days apart. Initial response was defined as platelet counts of ≥30 × 10\^9/L and a 2-fold increase from the Baseline platelet count at analysis visit 5.
Time frame: Up to 24 weeks
Population: FAS: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Efgartigimod PH20 SC | Percentage of Participants With a Platelet Count International Working Group (IWG) Response | IWG Complete Response | 10.2 percentage of participants |
| Efgartigimod PH20 SC | Percentage of Participants With a Platelet Count International Working Group (IWG) Response | IWG Response | 28.5 percentage of participants |
| Efgartigimod PH20 SC | Percentage of Participants With a Platelet Count International Working Group (IWG) Response | Initial Response | 19.7 percentage of participants |
| Placebo PH20 SC | Percentage of Participants With a Platelet Count International Working Group (IWG) Response | IWG Complete Response | 11.4 percentage of participants |
| Placebo PH20 SC | Percentage of Participants With a Platelet Count International Working Group (IWG) Response | IWG Response | 20.0 percentage of participants |
| Placebo PH20 SC | Percentage of Participants With a Platelet Count International Working Group (IWG) Response | Initial Response | 17.1 percentage of participants |
Comparison: IWG Complete Response95% CI: [-11.8, 7.3]
Comparison: IWG Response95% CI: [-4.6, 20.2]
Comparison: Initial Response95% CI: [-9.7, 13.3]
Secondary
Rate of Receipt of Rescue Therapy (Rescue Per Participant Per Month) in the Overall Population
Rescue therapy was defined as an occurrence where the participant needed treatment with 1 or more rescue treatments. An occurrence was defined as a period of maximum 5 days where 1 or more rescue treatments were administered simultaneously or consecutively to the trial participant. The following rescue treatments were permitted: methylprednisolone, dexamethasone, prednisone, normal immunoglobulins, anti-D (Rho) immunoglobins, or platelet transfusions.
Time frame: Up to 24 weeks
Population: FAS: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efgartigimod PH20 SC | Rate of Receipt of Rescue Therapy (Rescue Per Participant Per Month) in the Overall Population | 0.25 rescues per participant per month | Standard Deviation 0.553 |
| Placebo PH20 SC | Rate of Receipt of Rescue Therapy (Rescue Per Participant Per Month) in the Overall Population | 0.17 rescues per participant per month | Standard Deviation 0.363 |
Secondary
Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population
All pharmacokinetic (PK) samples were collected predose, on the day of IMP administration.
Time frame: Predose on Weeks 1, 2, 3, 17, 19, 21, 23, and 24
Population: PK Analysis Set: Safety analysis set excluding placebo participants and including participants with at least one serum post dose PK measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population | Week 1 | 13.2 μg/mL | Standard Deviation 6.46 |
| Efgartigimod PH20 SC | Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population | Week 2 | 16.6 μg/mL | Standard Deviation 8.17 |
| Efgartigimod PH20 SC | Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population | Week 3 | 17.0 μg/mL | Standard Deviation 7.95 |
| Efgartigimod PH20 SC | Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population | Week 17 | 15.1 μg/mL | Standard Deviation 8.54 |
| Efgartigimod PH20 SC | Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population | Week 19 | 15.4 μg/mL | Standard Deviation 7.43 |
| Efgartigimod PH20 SC | Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population | Week 21 | 15.1 μg/mL | Standard Deviation 8.86 |
| Efgartigimod PH20 SC | Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population | Week 23 | 14.9 μg/mL | Standard Deviation 7.79 |
| Efgartigimod PH20 SC | Serum Efgartigimod Trough Concentration (Ctrough) in the Overall Population | Week 24 | 14.7 μg/mL | Standard Deviation 8.1 |
Secondary
Time to Platelet Count Response in the Overall Population
Time to platelet count response, defined as the time to have 2 consecutive platelet counts of ≥50 × 10\^9/L via Kaplan-Meier estimates.
Time frame: Up to 24 weeks
Population: FAS: All randomized participants. Participants with no occurrence of platelet count response, early discontinuation of treatment, or dose and/or frequency of concurrent ITP therapy increased or a new ITP therapy were censored. If multiple censoring conditions apply, the earliest censoring date is considered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod PH20 SC | Time to Platelet Count Response in the Overall Population | NA days |
| Placebo PH20 SC | Time to Platelet Count Response in the Overall Population | NA days |
Secondary
Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population
A titer was determined in the samples with a positive assay response.
Time frame: Weeks 3, 7, 11, 15, 19, 23, 24, SEFU1 (up to Week 29), and SEFU2 (up to Week 33)
Population: SAF: All participants who received at least 1 dose or part of a dose with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 7: ADA Against Efgartigimod Titer | 1.0 titer | — |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 11: ADA Against rHuPH20 Titer | 2204.8 titer | Standard Deviation 1297.43 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | SEFU1: ADA Against Efgartigimod Titer | 2.5 titer | Standard Deviation 1.5 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 15: ADA Against rHuPH20 Titer | 3209.3 titer | Standard Deviation 1325.96 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | SEFU2: ADA Against Efgartigimod Titer | 17.0 titer | Standard Deviation 15 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 19: ADA Against rHuPH20 Titer | 3742.7 titer | Standard Deviation 1414.15 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 3: ADA Against rHuPH20 Titer | 12.7 titer | Standard Deviation 2.53 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 23: ADA Against rHuPH20 Titer | 5936.6 titer | Standard Deviation 2180.33 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 24: ADA Against Efgartigimod Titer | 16.3 titer | Standard Deviation 8.95 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 24: ADA Against rHuPH20 Titer | 4731.3 titer | Standard Deviation 1898.96 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 7: ADA Against rHuPH20 Titer | 645.9 titer | Standard Deviation 314.79 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | SEFU1: ADA Against rHuPH20 Titer | 5122.5 titer | Standard Deviation 5117.5 |
| Efgartigimod PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | SEFU2: ADA Against rHuPH20 Titer | 5160.0 titer | Standard Deviation 5080 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 7: ADA Against rHuPH20 Titer | 14.4 titer | Standard Deviation 4.27 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 7: ADA Against Efgartigimod Titer | 11.3 titer | Standard Deviation 10.33 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 11: ADA Against Efgartigimod Titer | 6.3 titer | Standard Deviation 4.84 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 15: ADA Against Efgartigimod Titer | 8.5 titer | Standard Deviation 7.5 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 23: ADA Against Efgartigimod Titer | 2.0 titer | — |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 24: ADA Against Efgartigimod Titer | 1.0 titer | Standard Deviation 0 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 3: ADA Against rHuPH20 Titer | 14.1 titer | Standard Deviation 3.15 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 3: ADA Against Efgartigimod Titer | 16.5 titer | Standard Deviation 15.5 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 11: ADA Against rHuPH20 Titer | 11.4 titer | Standard Deviation 2.37 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 15: ADA Against rHuPH20 Titer | 15.7 titer | Standard Deviation 2.02 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 19: ADA Against rHuPH20 Titer | 49.1 titer | Standard Deviation 27.87 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 23: ADA Against rHuPH20 Titer | 58.3 titer | Standard Deviation 27.83 |
| Placebo PH20 SC | Titers of Antibodies to Efgartigimod and/or rHuPH20 in the Overall Population | Week 24: ADA Against rHuPH20 Titer | 69.1 titer | Standard Deviation 26.6 |