Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC)

Tahapan Penelitian : Awal
Sponsor:
Mitra Pelaksana:
INA-RESPOND; RSUD Dr. Soetomo; RSU Kab Tangerang & RSUPN Dr.Cipto Mangunkusumo
No Registry
INA-N9A8PM2
Tanggal Input Registry : 10-12-2020

21-12-2020
The primary objective is to compare the clinical status of participants in the hIVIG + SOC and placebo + SOC groups on Day 7 using an ordinal outcome with 7 mutually exclusive categories. On Day 7, the worst of the 7 categories the participant was in that day will constitute the primary outcome. The 7 categories are: 7. Death 6. End-organ failure 5. Life-threatening end-organ dysfunction 4. Serious end-organ dysfunction 3. Moderate end-organ dysfunction 2. Limiting symptoms due to COVID-19 1. No limiting symptoms due to COVID-19
SOC over the 28 days follow-up period for outcomes listed below. Because there is no established endpoint for evaluating the clinical efficacy of treatments for COVID-19, other clinically relevant outcomes, including outcomes used in other COVID-19 treatment trials, will be recorded. Thus, the randomized groups can be compared for multiple outcomes, and results can be compared or combined with other trials. Many of the endpoints used in other trials are ordinal outcomes or are defined based on a dichotomy of an ordinal outcome and assessed at a single follow-up time point or as a time-to-event outcome. 1. All-cause mortality through Day 28. 2. The primary ordinal outcome on Days 3, 5, 14 and 28. 3. Change in National Early Warning Score (NEWS) (from baseline at Day 4. Time to the 3 least favorable categories of the primary outcome measure. 5. Time to the 2 most favorable categories of the primary outcome measure. SOC over the 28 days follow-up period for outcomes listed below. Because there is no established endpoint for evaluating the clinical efficacy of treatments for COVID-19, other clinically relevant outcomes, including outcomes used in other COVID-19 treatment trials, will be recorded. Thus, the randomized groups can be compared for multiple outcomes, and results can be compared or combined with other trials. Many of the endpoints used in other trials are ordinal outcomes or are defined based on a dichotomy of an ordinal outcome and assessed at a single follow-up time point or as a time-to-event outcome. 1. All-cause mortality through Day 28. 2. The primary ordinal outcome on Days 3, 5, 14 and 28. 3. Change in National Early Warning Score (NEWS) (from baseline at Day 4. Time to the 3 least favorable categories of the primary outcome measure. 5. Time to the 2 most favorable categories of the primary outcome measure. 6. Hospitalization status (a binary outcome, alive and discharged from the hospital to home or rehabilitation versus dead or hospitalized) at Days 7, 14 and 28. 7. Time to discharge (this is similar to the recovery outcome used in the ACTT-1 trial40) 8. Days alive outside of a hospital through Day 28 9. Pulmonary only components of the primary outcome measure at Days 3, 5, 7, 14 and 28 10. Thrombotic components of the primary outcome measure (stroke, myocardial infarction, venous and arterial thrombosis or embolism, plus disseminated intravascular coagulation) at Days 3, 5, 7, 14, and 28. 11. Outcomes assessed in other treatment trials of COVID-19 for hospitalized participants in order to facilitate cross trial comparisons and overviews, e.g., 6-, 7- and 8- category ordinal scales at days 7, 14 and 28; and binary outcomes defined by improvement or worsening based on the primary ordinal outcome and ordinal outcomes used in other trials. 12. Clinical organ dysfunction defined by new onset of any one or more of the following conditions (or requirement for the following therapies) through Day 28. 13. Safety and tolerability will be assessed using outcomes described above (e.g., mortality and thrombotic outcomes) and also assessed by the following outcomes: a. A composite of incident grade 3 and 4 events (not limited to a laboratory abnormality), SAEs (see Section10.1.2), or death through Day 7 (primary safety endpoint) b. Infusion reactions of any grade severity during the infusion and 2 hours post-infusion, and percentage of participants for whom the infusion was interrupted or stopped prior to completion c. SAEs or deaths through Day 28 d. Prevalence of adverse events of any grade on Days 1, 3, 7 and 28. 14. Change in immunoglobulin levels (IgG, IgG subclasses, IgM, IgA) and neutralizing antibody titers from baseline to Days 1, 2, 3, 7, 28 and 90. 15. The primary endpoint by duration of symptoms at study entry. This is a key subgroup analysis. For those with shorter duration of time since symptom onset, the treatment effect is hypothesized to be greater than among participants who have had symptoms for a longer period of time. This hypothesis assumes that disease progression among those with longer duration of symptoms at study entry will be primarily determined by organ damage that has already occurred instead of ongoing viral replication. In addition, it is assumed that the natural antibody response to SARS-CoV-2 infection is likely to be greater at entry for those with longer symptom duration, and this would diminish the treatment difference between the hIVIG and placebo groups over the week following infusion. Given the inclusion criteria of ≤ 12 days, we anticipate the upper quartile will be 8-10 days (75% of participants will have symptom duration < 8 to 10 days). In ACCT-1, a more severely ill target population than studied here, there was no limit to the duration of symptoms and the median was 9 days (interquartile range, 6 to 12).40 The quartile definitions for duration of symptoms will be determined following the completion of enrollment, and will be stated in the data analysis plan. 16. The primary endpoint for other subgroups defined by the characteristics measured at baseline will also be assessed.
 
Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC)
An International Multicenter, Adaptive, Randomized Double-Blind, Placebo-Controlled Trial of the Safety, Tolerability and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Hospitalized Patients at Onset of Clinical Progression of COVID-19
Eksperimental
• Drug: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) • Other: Placebo • Drug: Remdesivir
500
 

Inclusion Criteria:

1.SARS-CoV-2 infection documented by PCR or other nucleic acid test (NAT) within 3 days prior to randomization OR documented by NAT more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection 2.Symptomatic COVID-19 disease 3.Duration of symptoms attributable to COVID-19 ≤ 12 days 4.Requiring inpatient hospital medical care for clinical manifestations of COVID-19 (admission for public health or quarantine only is not included) 5.Age ≥ 18 years 6.Willingness to abstain from participation in other COVID-19 treatment trials until after study Day 7 7.Provision of informed consent by participant or legally authorized representative

Exclusion Criteria:

1.Prior receipt of SARS-CoV-2 hIVIG or convalescent plasma from a person who recovered from COVID-19 at any time 2.Prior receipt of standard IVIG (not hyperimmune to SARS-CoV-2) within 45 days 3.Current or predicted imminent (within 24 hours) requirement for any of the following: •Invasive ventilation •Non-invasive ventilation •Extracorporeal membrane oxygenation •Mechanical circulatory support •Continuous vasopressor therapy 4.History of allergy to IVIG or plasma products 5.History of selective IgA deficiency with documented presence of anti-IgA antibodies 6.Any medical conditions for which receipt of the required volume of intravenous fluid may be dangerous to the patient 7.Any of the following thrombotic or procoagulant disorders: •Acute coronary syndromes, cerebrovascular syndromes and pulmonary or deep venous thrombosis within 28 days of randomization •History of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome 8.Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments
 
No. LB.02.01/2/KE.633/2020 tertanggal 9 November 2020
On process
No. RG.01.061.3.12.20.41 Tertanggal 8 December 2020
INSIGHT-013 ITAC
Dr. Muhammad Karyana, M.Kes