A Study to Evaluate the Efficacy and Safety of Efgartigimod PH20 Subcutaneous in Adult Patients With Primary Immune Thrombocytopenia

Phase 3

Completed

Conditions: Primary Immune Thrombocytopenia

Interventions: Biological: Efgartigimod PH20 SC
Other: Placebo PH20 SC

Registration Number: NCT04687072

Lead Sponsor: argenx

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 207

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Efgartigimod PH20 SC	Efgartigimod PH20 SC	Patients receiving efgartigimod PH20 SC treatment
Placebo PH20 SC	Placebo PH20 SC	Patients receiving placebo PH20 SC treatment

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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.
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).
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.
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.

Trial Locations

Locations (200): Investigator Site 0010116
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Springdale, Arkansas, United States
Investigator site 0010036
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Los Angeles, California, United States
Investigator Site 0010045
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Washington, District of Columbia, United States
Investigator Site 0010104
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Weston, Florida, United States
Investigator site 0010112
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Chicago, Illinois, United States
Investigator site 0010193
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Chicago, Illinois, United States
Investigator Site 0010079
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Lisle, Illinois, United States
Investigator Site 0010062
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Fort Wayne, Indiana, United States
Investigator site 0010042
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Iowa City, Iowa, United States
Investigator Site 0010083
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Detroit, Michigan, United States
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Investigator Site 0010116
🇺🇸Springdale, Arkansas, United States