A Phase 2 Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Efficacy and Safety of Efgartigimod IV in Adult Patients With Post-COVID-19 Postural Orthostatic Tachycardia Syndrome (POTS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- argenx
- 入组人数
- 53
- 试验地点
- 11
- 主要终点
- Change From Baseline to Week 24 in the COMPASS 31 (2-week Recall Version)
研究概览
简要总结
The study aims to investigate the safety, tolerability, efficacy, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of efgartigimod compared to placebo in participants with post-COVID-19 postural orthostatic tachycardia syndrome (POTS) (post-COVID-19 POTS).
详细描述
The study aims to investigate the safety, tolerability, efficacy, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of efgartigimod compared to placebo in participants with post-COVID-19 postural orthostatic tachycardia syndrome (POTS) (post-COVID-19 POTS). Efgartigimod may be a viable treatment option for individuals diagnosed with post-COVID-19 POTS because it has been shown to reduce IgG levels, including IgG autoantibodies, which may underlie some of the autonomic disease manifestations in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Reached the age of consent when signing the informed consent form
- •Capable of providing signed informed consent and complying with protocol requirements
- •Diagnosed with new-onset POTS post-COVID-19 established by the following:
- •History of COVID-19 based on a previous positive test result from either laboratory-confirmed COVID-19 test (eg, a PCR test) or non-laboratory-confirmed COVID-19 test (eg, rapid antigen test); this positive result may be either documented or patient-reported
- •Tilt table or orthostatic vital sign measurements during screening consistent with consensus criteria: sustained HR increase of ≥30 bpm within 10 min of standing or head up tilt (≥40 bpm for individuals aged 18 to 19 years) and/or HR reaching >120 bpm within 10 min; absence of sustained 20 mmHg decrease in systolic blood pressure (SBP)
- •Ongoing symptoms of POTS confirmed by the investigator with at least 3 symptoms in each of the following areas lasting longer than 12 weeks after either diagnosis of COVID-19 or after hospital discharge for COVID-19:
- •i. Vasomotor symptoms: fatigue, orthostatic intolerance, brain fog, exertional dyspnea, difficulty with concentration, venous pooling, and exercise intolerance ii. Sympathetic over-compensation symptoms: palpitation, heat intolerance, nausea with or without vomiting, insomnia, anxiety, lack of appetite, chest pain, and diaphoresis
- •COMPASS 31 ≥35 at screening
- •Agree to use contraceptives consistent with local regulations regarding the methods of contraception for those participating in clinical studies and the following:
- •Male participants: No male contraception is required Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before receiving IMP. Contraceptive requirements.
- •Body mass index (BMI) <35 kg/m2
排除标准
- •Diagnosis of or receiving treatment for the following conditions before COVID-19: peripheral neuropathy, POTS, myalgic encephalomyelitis encephalitis/chronic fatigue syndrome, Ehlers Danlos syndrome confirmed by genetic testing, autonomic neuropathy, multiple sclerosis, stroke, spinal cord injury, or any known lesions in the central nervous system by imaging or neurological exam
- •History of or currently being treated for clinically significant ongoing cardiac arrythmia, heart failure, myocarditis, pulmonary embolism requiring anticoagulation, pulmonary fibrosis, or critical illness-related polyneuropathy or myopathy
- •Known autoimmune disease that, in the investigator's judgment, would interfere with an accurate assessment of clinical symptoms of post-COVID-19 POTS or puts the participant at undue risk
- •Known HIV disease or common variable immunodeficiency
- •History of malignancy unless considered cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of IMP. Adequately-treated participants with the following cancers may be included at any time:
- •Basal cell or squamous cell skin cancer
- •Carcinoma in situ of the cervix
- •Carcinoma in situ of the breast
- •Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
- •Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection or positive SARS-CoV-2 PCR test at screening
- •Positive serum test at screening for an active infection with any of the following:
- •Hepatitis B virus (HBV) that is indicative of an acute or chronic infection, unless associated with a negative HB surface antigen (HBsAg) or negative HBV DNA test
- •Hepatitis C virus (HCV) based on HCV antibody assay unless a negative RNA test is available
- •A medical condition that could confound the results of the study or put the participant at undue risk in the investigator's judgment
- •Clinically significant disease, recent major surgery (within 3 months of screening), or intends to have surgery during the study; or any other condition that in the opinion of the investigator could confound the results of the study or put the participant at undue risk
- •Total IgG <4 g/L at screening
- •Received within 12 weeks or 5 half-lives (whichever is longer) before screening an investigational product
- •Received within 12 weeks before screening either intravenous immunoglobulin (Ig) IV or SC or plasmapheresis/plasma exchange (PLEX)
- •Received a live or live-attenuated vaccine less than 4 weeks before screening
- •Known hypersensitivity to IMP or 1 of its excipients
- •Previously participated in an efgartigimod clinical study and received at least 1 dose of IMP
- •Currently participating in another interventional clinical study
- •History (within 12 months of screening) of or current alcohol, drug, or medication abuse
- •Pregnant or lactating or intends to become pregnant during the study
- •Unwilling to remain on a stable regimen of medications during the study
- •Unwilling to avoid initiation of new physical rehabilitation or other physician-prescribed exercise programs during the 24-week treatment period
研究组 & 干预措施
Efgartigimod
Receive efgartigimod IV 10mg/kg during weekly infusions during a treatment period of 24 weeks
干预措施: Efgartigimod (Drug)
Placebo
Receive a matching placebo during weekly infusions during a treatment period of 24 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to Week 24 in the COMPASS 31 (2-week Recall Version)
时间窗: Baseline (Day 1) and Week 24
Composite Autonomic Symptom Score (COMPASS) 31 modified version (2-week recall) is a self-rated questionnaire to evaluate the severity and distribution of autonomic symptoms in various autonomic nerve disorders. It consists of 31 questions in 6 weighted domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal {GI}-mixed upper and diarrhea, bladder, and pupillomotor). A weighted total score of 0 (mild) to 100 (severe) was determined by adding a maximum raw score for each domain. Higher scores indicated a more severe degree of autonomic symptoms.
Change From Baseline to Week 24 in the MaPS
时间窗: Baseline (Day 1) and Week 24
The Malmö POTS Symptom Score (MaPS) score is a dedicated POTS symptom scoring questionnaire. The score consists of 12 questions that assess symptom burden related (tachycardia, palpitations, dizziness, presyncope) and unrelated to orthostatic intolerance (GI symptoms, insomnia, concentration difficulties). Participants graded their symptoms for the past 7 days using a visual analog scale ranging from 0 (no symptoms) to 10 (worst possible). The total score was calculated by summing up the items/individual items and range was 0 to 120 points, with higher scores indicating more severe symptoms.
Number of Participants With TEAEs and TESAEs
时间窗: From the first dose of study drug (Day 1) up to 60 days post last dose of study drug, up to 236 days
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or any other medically important event. Treatment-emergent adverse events (TEAEs) were defined as AEs with onset on or after the first administration of study drug up to and including 60 days after the last study drug administration.
次要结局
- Percentage of Participants With Improved PGI-S at Week 24(Baseline (Day 1) and Week 24)
- Percentage of Participants With Improved in PGI-C at Week 24(Baseline (Day 1) and Week 24)
- Change From Baseline to Week 24 in the PROMIS Fatigue Short Form 8a(Baseline (Day 1) and Week 24)
- Change From Baseline to Week 24 in the PROMIS Cognitive Function Short Form 6a(Baseline (Day 1) and Week 24)
- Percent Change From Baseline in Total IgG Levels at Week 24(Baseline (Day 1) and Week 24)
- Serum Concentration of Efgartigimod(Pre-dose and post-dose at Baseline (Day 1), Weeks 1, 4, 12 and at Week 24)
- Number of Participants With ADAs Against Efgartigimod(Up to Week 24)