Convalescent Plasma as Treatment for Subjects With Early COVID-19 Infection

COVID-19 Clinical Trial

Official title:

Phase II Randomized Study of Convalescent Plasma From Recovered COVID-19 Donors Collected by Plasmapheresis as Treatment for Subjects With Early COVID-19 Infection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04456413
• Other study ID #: Pro2020-0542
• Status: Terminated
• Phase: Phase 2
• Start date: November 6, 2020
• Est. completion date: May 4, 2021

Study information

• Verified date: September 2023
• Source: Hackensack Meridian Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

• This is a phase II randomized study of convalescent plasma for the treatment of non-immune individuals with COVID-19 infection at high risk of complications.

• Subjects will be considered as having completed the study after 2 months (+/- 5) days, unless consent withdrawal or death occurs first.

• Subjects will be randomized to receiving convalescent plasma or best supportive care.

• Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.

• The final analysis will be conducted once the last subject completes the 2-month visit or withdraws from the study.

Description:

Overall study design

• This is a phase II randomized study of convalescent plasma for the treatment of non-immune individuals with COVID-19 infection at high risk of complications.

• Subjects will be considered as having completed the study after 2 months (+/- 5) days, unless consent withdrawal or death occurs first.

• Subjects will be randomized to receiving convalescent plasma or best supportive care.

• Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.

• The final analysis will be conducted once the last subject completes the 2-month visit or withdraws from the study.

A total of 306 subjects will be recruited, 153 for each arm. If a patient in the best supportive care arm requires hospitalization, the patient will be eligible to receive convalescent plasma if requested and/or deemed medically appropriate by the admitting physician.

Overall study duration

• The study begins when the first subject (donor or recipient) signs the informed consent. The study will end once the last enrolled subject completes the study (likely a recipient).

• The expected duration of the study is approximately 12 months.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: May 4, 2021
• Est. primary completion date: April 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Donor Eligibility Criteria:

• Age 18-60

• A history of a positive nasopharyngeal swab for COVID-19 or a history of positive antibody titer test.

• At least 14 days from resolution of COVID-19-associated symptoms including fevers.

• A negative nasopharyngeal swab (or similar test) for COVID-19

• anti-SARS-CoV2 titers >1:500

• Adequate venous access for apheresis

• Meets donor eligibility criteria in accordance to Hackensack University Medical Center (HUMC) Collection Facility at the John Theurer Cancer Center (JTCC) if collecting at the JTCC, and all regulatory agencies as describes in SOP 800 01.

• Required testing of the donor and product must be performed in accordance to FDA regulations (21 CFR 610.40), and the donation must be found suitable (21 CFR 630.30)

Recipient Eligibility Criteria:

• Patient age >30 years old, newly diagnosed with a COVID-19 infection with onset of first symptoms < 96 hours.

• And least one other high-risk feature:

1. Age > 65

2. BMI 30 or above

3. Hypertension, defined as SBP above 140 or DBP above 90, or requiring medication for control.

4. Coronary artery disease (history, not ECG changes only)

5. Congestive heart failure

6. Peripheral vascular disease (includes aortic aneurysm >= 6 cm)

7. Cerebrovascular disease (history of CVA or TIA)

8. Dementia

9. Chronic pulmonary disease

10. Liver disease (such as portal hypertension, chronic hepatitis)

11. Diabetes (excludes diet-controlled alone)

12. Moderate or severe renal disease defined as having a GFR < 60 mL/min

13. Cancer (exclude if > 5 year in remission)

14. AIDS (not just HIV positive)

Recipient exclusion criteria:

• History of severe transfusion reaction to plasma products

• Need for oxygen supplementation

• Positive test for COVID-19 antibodies

• Chemotherapy-induced neutropenia (ANC < 0.5 x 103/mcL)

• Immunosuppressive medications except for prednisone (or steroid equivalent) > 10 mg daily.

• Performance status < 50 by KPS

• Pneumonia by radiographic evaluation

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• Convalescent Plasma
Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection

Other:
• Best Supportive Care
Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.

Locations

Country	Name	City	State
United States	Hackensack University Medical Center	Hackensack	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Hackensack Meridian Health	United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (22)

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma Product's Cytokine Level Assessment	Univariate test will be performed in terms of identifying the association between exploratory objective and the hospitalization rate, Mantel-Haenszel test for categorical variables, and t-test or its non-parametric version for the continuous variables based on the normalized of the data.	Day 0
Other	Plasma Product's Mannose-binding Lectin (MBL) Level Assessment		Day 0
Other	Plasma Product's Procalcitonin (PCT) Level Assessment		Day 0
Other	Plasma Product's C-reactive Protein (CRP) Level Assessment		Day 0
Other	Plasma Product's Human Neutrophil Lipocalin (HNL) Level Assessment		Day 0
Other	Plasma Product's Annexin V Level Assessment		Day 0
Other	Plasma Product's Surfactant Protein D (SP-D) Level Assessment		Day 0
Other	Plasma Product's microRNA Level Assessment		Day 0
Other	Plasma Product's Immunoglobulin Level Assessment		Day 0
Other	Patients' Cytokines Levels Assessment at +2 and +4 Weeks Post Randomization		2 Weeks and 4 Weeks
Other	Patients' Chemokines Levels Assessment at +2 and +4 Weeks Post Randomization		2 Weeks and 4 Weeks
Other	Rates of Adverse Events Associated With Convalescent Plasma Infusion.	Safety assessment will be performed on infusion day for the Treatment group (immediately post infusion), and for all patients on randomization day +3 and +7 days (by telephone, closest business day is acceptable), +2 weeks (+/- 3 days), +4 weeks (+/- 3 days).	Day 3 and 7, Weeks 2 and 4
Primary	Hospitalization Rate	The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test.	10 Days
Secondary	Time to Symptoms Resolution	The time to symptoms resolution is defined as the time in days from therapies initiation to the first documented symptoms resolution as assessed by a local site. Patients whose symptoms are not resolved, or result in death, or lost follow-up on the designed follow-up date, will be censored on that date.	2 Months
Secondary	Overall Survival Rate	Overall survival (OS) will be defined as Rate of death	2 Months
Secondary	Rate of Virologic Clearance by Nasopharyngeal Swab at 2 Weeks		2 Weeks
Secondary	Rate of Nasopharyngeal Swab Positivity in Donors		2 Months
Secondary	Rate of Donor Titers Level	Rate of Donor Titer Levels >1:1000	2 Months
Secondary	Impact of Donor Titers Level on Efficacy		2 Months
Secondary	Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months.		Prior to treatment, 2 Weeks, 4 Weeks, and 2 Months
Secondary	Rate of Virologic Clearance by Nasopharyngeal Swab at 4 Weeks		4 Weeks