ANTI-SARS-COV-2 POLYCLONAL HYPERIMMUNE GLOBULIN for COVID-19

Stratification factors

• Standard of care treatment stratum: whether a direct-acting antiviral (DAA) or other anti-SARS-CoV-2 agent was prescribed as part of SOC (stratum 1 = not prescribed; stratum 2 = prescribed)

Inclusion criteria

• {"criterion_text":"- Clinical risk based on age ≥ 55 years or an adult (age ≥ 18 years) with an immunosuppressed condition.\n- 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.\n- Within ≤5 days from symptom onset, if symptomatic from current SARS-CoV-2 infection.\n- 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).\n- Participant provides written informed consent prior to study procedures and understands and agrees to adhere to planned study procedures through Day 28."}

Exclusion criteria

• {"criterion_text":"- Asymptomatic and had prior symptoms from the current infection that have now resolved (for >24 hours).\n- 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.\n- Asymptomatic and has received a vaccination for COVID-19 (≥1 dose).\n- Undergoing evaluation for possible admission to hospital for medical management (this does not include evaluation of possible hospitalization for public health purposes).\n- 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).\n- 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).\n- 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.\n- History of hypersensitivity to blood, plasma or IVIG excipients.\n- Known IgA deficiency or anti-IgA antibodies.\n- Medical conditions for which receipt of a 300 mL volume of IV fluid from study treatment may pose specific risk to the patient (e.g., decompensated congestive heart failure)."}

Primary endpoints

• {"endpoint_text":"- Asymptomatic and no limitations in usual activity due to COVID-19","definition_or_measurement_approach":"Measured as a category on the clinical ordinal scale; primary comparison of clinical status after seven days using the ordinal scale (Day 7)."}
• {"endpoint_text":"- Mild COVID-19 illness or minor limitations to usual activity","definition_or_measurement_approach":"Measured as a category on the clinical ordinal scale; primary comparison of clinical status after seven days using the ordinal scale (Day 7)."}
• {"endpoint_text":"- Moderate COVID-19 illness and major limitations to usual activity","definition_or_measurement_approach":"Measured as a category on the clinical ordinal scale; primary comparison of clinical status after seven days using the ordinal scale (Day 7)."}
• {"endpoint_text":"- Severe COVID-19 or other serious disease manifestation","definition_or_measurement_approach":"Measured as a category on the clinical ordinal scale; primary comparison of clinical status after seven days using the ordinal scale (Day 7)."}
• {"endpoint_text":"- Critical illness from COVID-19 or Death","definition_or_measurement_approach":"Measured as a category on the clinical ordinal scale; primary comparison of clinical status after seven days using the ordinal scale (Day 7)."}

Secondary endpoints

• {"endpoint_text":"- All-cause hospitalization or death through 28 days.","definition_or_measurement_approach":"Event occurrence through Day 28 (hospitalization or death)."}
• {"endpoint_text":"- All-cause mortality through 28 days.","definition_or_measurement_approach":"Death from any cause through Day 28."}
• {"endpoint_text":"- Significant disease progression through 28 days, using a time to event analysis with outcome defined by fulfilling criteria for category 4 or 5 on the ordinal scale.","definition_or_measurement_approach":"Time-to-event analysis where event is meeting ordinal scale category 4 or 5 within 28 days."}
• {"endpoint_text":"- Distribution of ordinal scale outcome at Day 4, 14, and 28.","definition_or_measurement_approach":"Assessment of ordinal scale categories at Days 4, 14 and 28."}
• {"endpoint_text":"- The proportion of participants with any disease progression at Day 7, using a sliding dichotomous scale progression defined by a categorization on the ordinal scale that is worse than the status at entry.","definition_or_measurement_approach":"Proportion with worsening on ordinal scale relative to baseline at Day 7."}
• {"endpoint_text":"- The proportion of participants who progress to categories 3-5 on the clinical ordinal scale at Day 7 among participants in categories 1 or 2 of the ordinal scale at entry.","definition_or_measurement_approach":"Proportion of baseline category 1/2 participants who reach ordinal categories 3-5 by Day 7."}
• {"endpoint_text":"- The severity of progression during follow-up, defined by the worst health status achieved on the clinical ordinal scale at any point by Day 7, 14, and 28.","definition_or_measurement_approach":"Worst (maximum) ordinal scale status recorded through Days 7, 14 and 28."}
• {"endpoint_text":"- The proportion of participants that attain their pre-COVID health status without limitations in usual activity (i.e., category 1) at Day 7, 14, and 28.","definition_or_measurement_approach":"Proportion achieving ordinal category 1 (pre-COVID health status) at Days 7, 14 and 28."}
• {"endpoint_text":"- Change in quantitative measures of viral burden between Day 0 and Day 7, including serum antigen levels (e.g., nucleocapsid antigen) as well as by polymerase chain reaction (PCR) from nasal and saliva specimens.","definition_or_measurement_approach":"Change in viral load/serum antigen and PCR measures between Day 0 and Day 7."}
• {"endpoint_text":"- Change in SARS-CoV-2 antibody levels between Day 0 and Day 7, including subclasses and neutralizing titers.","definition_or_measurement_approach":"Change in antibody levels, subclasses and neutralizing titers from Day 0 to Day 7."}
• {"endpoint_text":"- Utilization of health care resources through 28 days, defined by the proportion of participants that had health care engagement for the purposes of medical evaluation and/or management of COVID-19 illness (e.g., via telehealth, clinic, urgent care, emergency room, or hospitalization).","definition_or_measurement_approach":"Proportion with any healthcare engagement for COVID-19 evaluation/management through 28 days."}
• {"endpoint_text":"- The severity of respiratory symptoms and dysfunction, as the worst status through 28 days, including: a) no respiratory symptoms, b) upper respiratory symptoms, c) lower respiratory symptoms without hypoxia, c) hypoxia requiring conventional oxygen supplementation by nasal canula, d) respiratory failure requiring high-flow oxygen delivery device or non-invasive ventilation, or e) respiratory failure requiring mechanical ventilation or extra-corporeal membrane oxygenation (ECMO).","definition_or_measurement_approach":"Worst respiratory symptom/dysfunction category recorded through Day 28 using specified categories."}
• {"endpoint_text":"- Hypoxemia through Day 7, as evaluated through participant assessments of saturation of oxygen (SpO2) levels. Comparisons between groups will consider differences in SpO2 levels as well as explore the frequency of levels that drop below clinical thresholds (e.g., <94% and <90% on room air for those without COPD or use of supplemental O2 prior to COVID-19).","definition_or_measurement_approach":"Participant-reported/assessed SpO2 levels through Day 7; group comparisons of mean/threshold frequencies (<94%, <90%)."}
• {"endpoint_text":"- Proportion of patients starting other treatments targeting COVID-19.","definition_or_measurement_approach":"Proportion initiating other COVID-19-targeted treatments during follow-up."}
• {"endpoint_text":"- Associations between changes in laboratory assessments from Day 0 to Day 7, and ordinal scale distribution and clinical outcomes over follow-up.","definition_or_measurement_approach":"Correlation/association analyses between laboratory changes (Day 0 to Day 7) and clinical ordinal outcomes over follow-up."}

Denmark

Earliest CTIS Part Ii Submission Date

05-03-2024

Latest Decision Or Authorization Date

10-12-2024

Processing Time Days

280

Number Of Sites

8

Number Of Participants

50

Greece

Earliest CTIS Part Ii Submission Date

05-03-2024

Latest Decision Or Authorization Date

17-12-2024

Processing Time Days

287

Number Of Sites

7

Number Of Participants

100

Spain

Earliest CTIS Part Ii Submission Date

05-03-2024

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

784

Number Of Sites

2

Number Of Participants

10

Primary sponsor

Full Name

University Of Minnesota

Organisation Type

Educational Institution

Country Of Registered Address

United States