A Study to Evaluate the Efficacy and Safety of Efgartigimod PH20 Subcutaneous in Adult Patients With Primary Immune Thrombocytopenia
- Conditions
- Primary Immune Thrombocytopenia
- Interventions
- Biological: Efgartigimod PH20 SCOther: 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
Not provided
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).
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.
Trial Locations
- Locations (200)
Investigator site 0010036
🇺🇸Los Angeles, California, United States
Investigator site 0010040
🇺🇸Columbus, Ohio, United States
Investigator Site 0010115
🇺🇸Pittsburgh, Pennsylvania, United States
Investigator Site 0300009
🇬🇷Thessaloníki, Greece
Investigator Site 9720013
🇮🇱Ashkelon, Israel
Investigator Site 9720012
🇮🇱Haifa, Israel
Investigator Site 9720008
🇮🇱Jerusalem, Israel
Investigator Site 0520007
🇲🇽Mexico, Mexico
Investigator Site 0400006
🇷🇴Bucuresti, Romania
Investigator Site 0400016
🇷🇴Cluj-Napoca, Romania
Investigator Site 0400007
🇷🇴Craiova, Romania
Investigator Site 0070015
🇷🇺Syktyvkar, Russian Federation
Investigator Site 3810008
🇷🇸Kragujevac, Serbia
Investigator Site 9720011
🇮🇱Jerusalem, Israel
Investigator Site 9720009
🇮🇱Tel Aviv, Israel
Investigator Site 0860012
🇨🇳Nanchang, China
Investigator Site 9950007
🇬🇪Tbilisi, Georgia
Investigator Site 3530002
🇮🇪Dublin, Ireland
Investigator Site 3530001
🇮🇪Galway, Ireland
Investigator Site 0300008
🇬🇷Athens, Greece
Investigator Site 0300010
🇬🇷Athens, Greece
Investigator Site 9620002
🇯🇴Amman, Jordan
Investigator Site 0810023
🇯🇵Shimotsuke, Japan
Investigator Site 0480026
🇵🇱Nowy Sącz, Poland
Investigator Site 0400009
🇷🇴Bucuresti, Romania
Investigator Site 0660001
🇹🇭Bangkok Noi, Thailand
Investigator Site 0660005
🇹🇭Bangkok, Thailand
Investigator Site 2160006
🇹🇳Sfax, Tunisia
Investigator Site 0900014
🇹🇷Kocaeli, Turkey
Investigator Site 0900017
🇹🇷Tekirdağ, Turkey
Investigator Site 0860009
🇨🇳Kunming, China
Investigator Site 0860011
🇨🇳Zhengzhou, China
Investigator Site 0010102
🇺🇸Minneapolis, Minnesota, United States
Investigator Site 0610005
🇦🇺Westmead, Australia
Investigator Site 0860014
🇨🇳Shanxi, China
Investigator site 0010112
🇺🇸Chicago, Illinois, United States
Investigator Site 0010104
🇺🇸Weston, Florida, United States
Investigator Site 0610010
🇦🇺Clayton, Australia
Investigator Site 3590017
🇧🇬Plovdiv, Bulgaria
Investigator Site 0860055
🇨🇳Huizhou, China
Investigator Site 9950006
🇬🇪Tbilisi, Georgia
Investigator Site 0300007
🇬🇷Patra, Greece
Investigator Site 0330009
🇫🇷Créteil, France
Investigator site 0490008
🇩🇪Essen, Germany
Investigator Site 0390037
🇮🇹Alessandria, Italy
Investigator site 0390014
🇮🇹Milan, Italy
Investigator Site 0330018
🇫🇷Montpellier, France
Investigator Site 9950008
🇬🇪Tbilisi, Georgia
Investigator Site 0390041
🇮🇹Napoli, Italy
Investigator Site 0390015
🇮🇹Novara, Italy
Investigator Site 0340007
🇪🇸Barcelona, Spain
Investigator Site 9950019
🇬🇪Tbilisi, Georgia
Investigator Site 3530003
🇮🇪Dublin, Ireland
Investigator Site 0270003
🇿🇦Johannesburg, South Africa
Investigator Site 0490012
🇩🇪Gießen, Germany
Investigator Site 9720010
🇮🇱Haifa, Israel
Investigator Site 0390011
🇮🇹Reggio Calabria, Italy
Investigator Site 0390043
🇮🇹Ferrara, Italy
Investigator Site 0390045
🇮🇹Meldola, Italy
Investigator site 0390018
🇮🇹Reggio Emilia, Italy
Investigator Site 0810054
🇯🇵Kumamoto, Japan
Investigator Site 0810017
🇯🇵Saitama, Japan
Investigator Site 0810052
🇯🇵Tokyo, Japan
Investigator Site 0810048
🇯🇵Tsukuba, Japan
Investigator Site 0810012
🇯🇵Ōgaki, Japan
Investigator Site 0520004
🇲🇽Chihuahua, Mexico
Investigator Site 0820008
🇰🇷Seoul, Korea, Republic of
Investigator Site 0480037
🇵🇱Skorzewo, Poland
Investigator Site 0480039
🇵🇱Toruń, Poland
Investigator Site 3510006
🇵🇹Braga, Portugal
Investigator Site 0470002
🇳🇴Bergen, Norway
Investigator Site 0070038
🇷🇺Nizhny Novgorod, Russian Federation
Investigator Site 0070039
🇷🇺Smolensk, Russian Federation
Investigator Site 0640002
🇳🇿Palmerston North, New Zealand
Investigator Site 0640005
🇳🇿Christchurch, New Zealand
Investigator Site 0270005
🇿🇦George, South Africa
Investigator Site 0340006
🇪🇸Barcelona, Spain
Investigator Site 3510005
🇵🇹Lisboa, Portugal
Investigator Site 3510001
🇵🇹Porto, Portugal
Investigator Site 0400005
🇷🇴Bucharest, Romania
Investigator Site 0400012
🇷🇴Bucuresti, Romania
Investigator Site 0270004
🇿🇦Observatory, South Africa
Investigator Site 3510007
🇵🇹Lisboa, Portugal
Investigator Site 0070006
🇷🇺Kaluga, Russian Federation
Investigator Site 3810006
🇷🇸Belgrade, Serbia
Investigator Site 0340037
🇪🇸Madrid, Spain
Investigator site 0340013
🇪🇸Sevilla, Spain
Investigator Site 0270001
🇿🇦Pretoria, South Africa
Investigator Site 0340023
🇪🇸Barcelona, Spain
Investigator Site 0070012
🇷🇺Tula, Russian Federation
Investigator Site 0340024
🇪🇸Alava, Spain
Investigator Site 0340036
🇪🇸Sabadell, Spain
Investigator Site 0270002
🇿🇦Randburg, South Africa
Investigator Site 8860001
🇨🇳New Taipei City, Taiwan
Investigator Site 0900003
🇹🇷Ankara, Turkey
Investigator Site 0660008
🇹🇭Bangkok, Thailand
Investigator Site 0660009
🇹🇭Khon Kaen, Thailand
Investigator Site 0900006
🇹🇷Ankara, Turkey
Investigator Site 0900016
🇹🇷Edirne, Turkey
Investigator Site 0900004
🇹🇷İzmir, Turkey
Investigator Site 8860003
🇨🇳Taoyuan, Taiwan
Investigator Site 0660002
🇹🇭Bangkok, Thailand
Investigator Site 0900007
🇹🇷Adapazarı, Turkey
Investigator Site 0660003
🇹🇭Bangkok, Thailand
Investigator Site 0660006
🇹🇭Pathum Thani, Thailand
Investigator Site 2160001
🇹🇳Sousse, Tunisia
Investigator Site 0900019
🇹🇷Trabzon, Turkey
Investigator Site 2160002
🇹🇳Tunis, Tunisia
Investigator Site 0900015
🇹🇷Ankara, Turkey
Investigator Site 0900018
🇹🇷Malatya, Turkey
Investigator Site 0900009
🇹🇷Samsun, Turkey
Investigator Site 0900008
🇹🇷Ankara, Turkey
Investigator Site 0900013
🇹🇷Istanbul, Turkey
Investigator Site 0900010
🇹🇷Mersin, Turkey
Investigator site 0440011
🇬🇧Bradford, United Kingdom
Investigator Site 0440005
🇬🇧Coventry, United Kingdom
Investigator Site 0440008
🇬🇧London, United Kingdom
Investigator Site 0440041
🇬🇧London, United Kingdom
Investigator Site 0440014
🇬🇧Truro, United Kingdom
Investigator Site 0340022
🇪🇸Murcia, Spain
Investigator Site 0340004
🇪🇸Valencia, Spain
Investigator Site 0010116
🇺🇸Springdale, Arkansas, United States
Investigator Site 3590015
🇧🇬Sofia, Bulgaria
Investigator Site 0610001
🇦🇺Hobart, Australia
Investigator site 0010193
🇺🇸Chicago, Illinois, United States
Investigator Site 0010062
🇺🇸Fort Wayne, Indiana, United States
Investigator site 0010042
🇺🇸Iowa City, Iowa, United States
Investigator Site 0010079
🇺🇸Lisle, Illinois, United States
Investigator Site 0010083
🇺🇸Detroit, Michigan, United States
Investigator Site 0010095
🇺🇸Oklahoma City, Oklahoma, United States
Investigator Site 0540001
🇦🇷Buenos Aires, Argentina
Investigator Site 0540003
🇦🇷Córdoba, Argentina
Investigator Site 0610002
🇦🇺Box Hill, Australia
Investigator Site 0540004
🇦🇷Buenos Aires, Argentina
Investigator Site 0610009
🇦🇺Adelaide, Australia
Investigator Site 0610004
🇦🇺Bedford Park, Australia
Investigator Site 0610012
🇦🇺Garran, Australia
Investigator Site 0610003
🇦🇺West Perth, Australia
Investigator Site 0610011
🇦🇺Perth, Australia
Investigator Site 0560003
🇨🇱Viña Del Mar, Chile
Investigator Site 0860003
🇨🇳Beijing, China
Investigator Site 0860013
🇨🇳Beijing, China
Investigator Site 0560002
🇨🇱Santiago, Chile
Investigator Site 0560004
🇨🇱Temuco, Chile
Investigator Site 0860008
🇨🇳Bengbu, China
Investigator Site 0860015
🇨🇳Shenzhen, China
Investigator Site 0860010
🇨🇳Wuhan, China
Investigator Site 0860001
🇨🇳Tianjin, China
Investigator Site 0860006
🇨🇳Wenzhou, China
Investigator Site 0860005
🇨🇳Zhejiang, China
Investigator Site 0450005
🇩🇰Roskilde, Denmark
Investigator Site 0860058
🇨🇳Zhenjiang, China
Investigator Site 0860002
🇨🇳Wuxi, China
Investigator site 0860062
🇨🇳Zhenjiang, China
Investigator Site 9720007
🇮🇱Petach Tikva, Israel
Investigator Site 0390032
🇮🇹Milan, Italy
Investigator Site 0390044
🇮🇹Napoli, Italy
Investigator Site 0390035
🇮🇹Potenza, Italy
Investigator Site 0390046
🇮🇹Rome, Italy
Investigator Site 0390033
🇮🇹Terni, Italy
Investigator Site 0390036
🇮🇹Varese, Italy
Investigator Site 0810056
🇯🇵Chiba, Japan
Investigator Site 0810015
🇯🇵Hirakata, Japan
Investigator Site 0810010
🇯🇵Hiroshima, Japan
Investigator Site 0810053
🇯🇵Kanagawa, Japan
Investigator Site 0810051
🇯🇵Kitakyushu, Japan
Investigator Site 0810018
🇯🇵Maebashi, Japan
Investigator Site 0810057
🇯🇵Morioka, Japan
Investigator Site 0810016
🇯🇵Shibukawa, Japan
Investigator Site 0810044
🇯🇵Yamanashi, Japan
Investigator Site 0810039
🇯🇵Shinagawa-Ku, Japan
Investigator Site 9620001
🇯🇴Irbid, Jordan
Investigator Site 0820005
🇰🇷Seongnam, Korea, Republic of
Investigator Site 0810038
🇯🇵Tama, Japan
Investigator Site 0820003
🇰🇷Seoul, Korea, Republic of
Investigator Site 0820006
🇰🇷Seoul, Korea, Republic of
Investigator Site 0820004
🇰🇷Seoul, Korea, Republic of
Investigator Site 0820007
🇰🇷Seoul, Korea, Republic of
Investigator Site 0520002
🇲🇽Aguascalientes, Mexico
Investigator Site 0520003
🇲🇽Monterrey, Mexico
Investigator Site 0520001
🇲🇽Oaxaca, Mexico
Investigator Site 0480013
🇵🇱Katowice, Poland
Investigator Site 0640001
🇳🇿Auckland, New Zealand
Investigator Site 0470003
🇳🇴Oslo, Norway
Investigator Site 0480014
🇵🇱Lublin, Poland
Investigator Site 0480033
🇵🇱Warszawa, Poland
Investigator Site 3510003
🇵🇹Coimbra, Portugal
Investigator Site 3510002
🇵🇹Lisboa, Portugal
Investigator Site 3510004
🇵🇹Porto, Portugal
Investigator Site 0400011
🇷🇴Sibiu, Romania
Investigator Site 0400008
🇷🇴Târgu-Mureş, Romania
Investigator Site 0070040
🇷🇺Kirov, Russian Federation
Investigator Site 0010045
🇺🇸Washington, District of Columbia, United States
Investigator Site 9950009
🇬🇪Tbilisi, Georgia
Investigator Site 9950011
🇬🇪Tbilisi, Georgia
Investigator Site 0070037
🇷🇺Novosibirsk, Russian Federation
Investigator Site 0070024
🇷🇺Pyatigorsk, Russian Federation
Investigator Site 0070025
🇷🇺Saint Petersburg, Russian Federation
Investigator Site 0070026
🇷🇺Moscow, Russian Federation
Investigator Site 0660004
🇹🇭Chiang Mai, Thailand