Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Minnesota

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

11 Nov 2021 → ongoing

Decision date (initial)

2024-03-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

University of Minnesota

External identifiers

EU CT number

2023-508105-24-00

EudraCT number

2021-001663-24

ClinicalTrials.gov

NCT04910269

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Among outpatients with recently diagnosed SARS-CoV-2 infection to compare the safety and efficacy of a single infusion of hyperimmune immunoglobulin (hIVIG) versus placebo, each given with standard of care (SOC), on clinical status after seven days. Two hypotheses will be tested to address this primary objective, which compares the primary endpoint among two study populations: 1) participants where a direct-acting antiviral (DAA) or other anti-SARS-CoV-2 agent was not prescribed as part of SOC treatment (stratum 1, see Section 6.1); and 2) all randomized participants (stratum 1 and stratum 2 combined). Stratum 2 is defined by prescribed treatments in SOC that include: DAA or other anti-SARS-CoV2 agents that are recommended for use by established national or international COVID-19 treatment guidelines. The hIVIG treatment will be considered superior to placebo if either of the two hypotheses are rejected.

Secondary objectives 1

1. Secondary objectives, including subgroup analyses and safety outcomes, will be addressed for all randomized participants and for those in stratum 1 and stratum 2 separately.

Conditions and MedDRA coding

COVID-19

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Clinical risk based on age ≥ 55 years or an adult (age ≥ 18 years) with an immunosuppressed condition.
2. 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.
3. Within ≤5 days from symptom onset, if symptomatic from current SARS-CoV-2 infection.
4. 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).
5. Participant provides written informed consent prior to study procedures and understands and agrees to adhere to planned study procedures through Day 28.

Exclusion criteria 10

1. Asymptomatic and had prior symptoms from the current infection that have now resolved (for >24 hours).
2. Asymptomatic and has received a vaccination for COVID-19 (≥1 dose).
3. Undergoing evaluation for possible admission to hospital for medical management (this does not include evaluation of possible hospitalization for public health purposes).
4. 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).
5. 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).
6. 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.
7. History of hypersensitivity to blood, plasma or IVIG excipients.
8. Known IgA deficiency or anti-IgA antibodies.
9. 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).
10. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

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 major limitations to usual activity
4. Severe COVID-19 or other serious disease manifestation
5. Critical illness from COVID-19 or Death

Secondary endpoints 15

1. All-cause hospitalization or death through 28 days.
2. All-cause mortality through 28 days.
3. 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.
4. Distribution of ordinal scale outcome at Day 4, 14, and 28.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Change in SARS-CoV-2 antibody levels between Day 0 and Day 7, including subclasses and neutralizing titers.
11. 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).
12. 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).
13. 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).
14. Proportion of patients starting other treatments targeting COVID-19.
15. Associations between changes in laboratory assessments from Day 0 to Day 7, and ordinal scale distribution and clinical outcomes over follow-up.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Minnesota

Sponsor organisation

University Of Minnesota

Address

2221 University Avenue Southeast Suite 200

City

Minneapolis

Postcode

55414-3075

Country

United States

Scientific contact point

Organisation

University Of Minnesota

Contact name

Rebecca Schoenecker

Public contact point

Organisation

University Of Minnesota

Contact name

Rebecca Schoenecker

Locations

3 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications