An International Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Outpatients in Early Stages of COVID-19
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 741
- 试验地点
- 91
- 主要终点
- Clinical Status
研究概览
简要总结
The primary objective of the Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC) (INSIGHT 012) trial is to compare the safety and efficacy of a single infusion of anti-COVID-19 hyperimmune intravenous immunoglobulin (hIVIG) versus placebo among adults with recently diagnosed severe acute respiratory syndrome - coronavirus 2 (SARS-CoV2) infection who do not require hospitalization. The primary endpoint of this double-blind randomized trial is a five-category ordinal outcome that assesses the participant's clinical status seven days after the infusion of hIVIG or placebo.
- Asymptomatic and no limitations in usual activity due to COVID-19
- Mild COVID-19 illness or minor limitations to usual activity
- Moderate COVID-19 illness and with major limitations to usual activity
- Severe COVID-19 or serious disease manifestation from COVID-19
- Critical illness from COVID-19 or Death
Two strata of participants will be identified for analysis purposes. Stratum 2 will be participants who receive direct-acting antivirals (DAAs) or other anti-SARS-CoV2 agents that are approved/available and recommended for use as part of standard of care (SOC), estimated to be about 20% of participants. Stratum 1 will be participants who do not receive this agents, estimated to be about 80% of participants.
详细描述
The primary objective will be addressed by testing two hypotheses aimed at assessing whether hIVIG + standard of care (SOC) is superior to placebo + SOC for the primary ordinal endpoint at Day 7. These hypotheses will be tested for the following two groups: a) among all randomized participants (stratum 1 and 2), and b) among only participants enrolled in stratum 1. For the primary analysis, overall type 1 error will be controlled at 5% by using a 2-sided significance level of 0.035 for each hypothesis. This significance level was obtained using the correlation between the test statistics for the proportional log odds ratio for all randomized participants and for this log odds ratio for those in stratum 1. This correlation was determined to be 0.895. With this approach hIVIG will be considered superior to placebo if either of the two hypotheses is rejected.
Participants will be randomized to a single infusion of an hIVIG product or placebo in a 1:1 allocation. Randomization will be stratified by study site pharmacy and the two SOC strata.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Clinical risk based on age ≥ 55 years or an adult (age ≥ 18 years) with an immunosuppressed condition.
- •Positive test for SARS-CoV-2 within ≤5 days (if >1 test, the first positive is within ≤5 days). Tests may include an institutional-based nucleic acid amplification test (NAAT), or any protocol-approved rapid test.
- •Within ≤5 days from symptom onset, if symptomatic from current SARS-CoV-2 infection.
- •Agrees to not participate in another clinical trial for the treatment or management of SARS-CoV-2 infection through Day 7, or until hospitalized or significant disease progression if prior to Day 7 (defined by ordinal category 4 or 5).
- •Participant provides written informed consent prior to study procedures, and understands and agrees to adhere to planned study procedures through Day
- •Ongoing immunosuppressive condition or immunosuppressive treatment, includes:
- •Steroids equivalent to prednisone > 10 mg/day for at least the last 28 days
- •Rheumatologic or autoimmune disorder treated with a biologic or non-biologic immunosuppressive therapy
- •Antirejection medicine after solid organ or stem cell transplantation
- •Cancer treatment with systemic chemotherapy, biologic and/or cell-based therapy in the last 12 months
- •Primary or acquired severe B- or T-lymphocyte immune dysfunction
- •HIV infection
- •Splenectomy or functional asplenia
排除标准
- •Asymptomatic and had prior symptoms from the current infection that have now resolved (for >24 hours).
- •Asymptomatic and has received a vaccination for COVID-19 (≥1 dose).
- •Undergoing evaluation for possible admission to hospital for medical management (this does not include evaluation of possible hospitalization for public health purposes).
- •Evidence of pneumonia and/or hypoxia due to COVID-19 (NOTE: chest imaging is not required, but if available it should not show new infiltrates suggestive of pneumonia; hypoxia is defined by new oxygen supplementation or increase above pre-illness level).
- •Prior receipt of immunoglobulin product or passive immune therapy for SARS-CoV-2 in the past 90 days (i.e., convalescent plasma, SARS-CoV-2 monoclonal antibodies, or any IVIG).
- •Any of the following thrombotic or procoagulant conditions or disorders:
- •acute coronary syndrome, cerebrovascular syndrome, pulmonary embolism, or deep venous thrombosis within 28 days of randomization.
- •prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antiphospholipid syndrome, or a deficiency in antithrombin III, protein C, or protein S.
- •History of hypersensitivity to blood, plasma or IVIG excipients.
- •Known immunoglobulin A (IgA) deficiency or anti-IgA antibodies.
- •In the opinion of the investigator, any condition for which participation would not be in the best interest of the participant or that could prevent or confound protocol assessments.
研究组 & 干预措施
Treatment Group
Participants in this group will receive the investigational treatment in addition to standard of care.
干预措施: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) (Biological)
Placebo Group
Participants in this group will receive a placebo in addition to standard of care.
干预措施: Placebo (Other)
结局指标
主要结局
Clinical Status
时间窗: 7 days
The primary outcome is to compare the safety and efficacy of a single infusion of hIVIG versus placebo on clinical status after seven days. Outcome will be reported as the percent of participants who fall into each of 5 clinical status categories as defined below. 1. Asymptomatic and no limitations in usual activity due to COVID-19 2. Mild COVID-19 illness or minor limitations to usual activity 3. Moderate COVID-19 illness and with major limitations to usual activity 4. Severe COVID-19 or serious disease manifestation from COVID-19 5. Critical illness from COVID-19 or Death
次要结局
- All-cause mortality through 28 days.(28 days)
- Ordinal Scale Distribution(4, 14, 28 days)
- Worst Status Through 28 Days(28 days)
- Significant Disease Progression(28 days)
- Disease Progression Through 7 Days(7 days)
- Significant Disease Progression Through 7 Days(7 days)
- Activity Limitations at Follow-up(7, 14, 28 days)
- Change in Viral Burden from Serum Antigen(7 days)
- Change in Viral Burden from PCR(7 days)
- Change in SARS-CoV-2 Antibody Concentration(7 days)
- Additional COVID-19 Treatment(28 days)
- All-cause hospitalization or death through 28 days.(28 days)
- Healthcare Utilization at Follow-up(28 days)
- Disease Progression at Follow-up(7, 14, 28 days)
- Hypoxemia Through Day 7(7 days)