Clinical trial NCT05173441: Human COVID-19 Immunoglobulin (COVID-HIG) Therapy for COVID-19 Patients
Official title: A Randomized, Double-blind, Placebo-controlled Phase II Exploratory Clinical Trial to Evaluate the Efficacy and Safety of Human COVID-19 Immunoglobulin (pH4) for Intravenous Injection (COVID-HIG) in the Treatment of Patients With COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID-19
immunoglobulin
COVID-HIG
SARS-CoV-2
2019nCov
hyperimmune globulin
Coronavirus disease 2019
passive immunotherapy
therapeutic
Lead sponsor: Beijing Tiantan Biological Products Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: China National Biotec Group Company Limited
name: Beijing Tiantan Biological Products Co., Ltd.
First posted: 2021-12-30
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A randomized, double-blind, placebo-controlled phase II exploratory clinical trial to evaluate the efficacy and safety of Human COVID-19 immunoglobulin (pH4) for intravenous injection (COVID-HIG) in the treatment of patients with COVID-19.

Detailed description: Eligible adault patients with confirmed COVID-19 will be randomized 1:1:1 to receive intravenous injections of High-dose COVID-HIG, Low-dose COVID-HIG or Placebo ( 0.9% sodium chloride injection). Patients in each arm will receive continued standard of care (SOC) therapy. The primary efficacy end point is the median time to clinical improvement (defined as clinical improvement of at least 2 points from baseline on the 7-point ordinal scale) observed from 0 to 28 days after the first administration.

Eligibility criteria: Inclusion Criteria:

1. ≥18 and \<65 years of age when signing the ICF, male or femal.
2. Positive testing by virologic test (SARS-CoV-2 virus nucleic acid test,result of RT-PCR within 3 days are accpetable) before randomization.
3. COVID-19 related clinical symptoms (fever or respiratory symptoms, etc.) progresses before randomization.
4. Inpatients with moderate or severe COVID-19 (severity is graded by FDA standard).
5. With early warning signs for severe/critical cases, meet any of the following indicators: ①Progressive exacerbation of hypoxemia or respiratory distress; ②Deterioration of tissue oxygenation or progressive hyperlactatemia. ③ Rapid decrease in lymphocyte count or steady increase in inflammatory markers such as IL-6, CRP, and ferritin. ④Significant increase of D-dimer and other related indexes of coagulation function. ⑤Chest imaging showing rapid progression of lung lesions.
6. Randomization should be within 10 days of COVID-19 symptoms onset.
7. Subjects (including their partners) have no pregnancy plan and voluntarily take effective contraceptive measures from signing ICF to 3 months after he/she finished the trial.
8. Willing to comply with the requirements, and cooperate when collecting of nasopharyngeal swabs and venous blood for testing according to the protocol; and willing to complete the study.
9. Able to consent, and willing to sign the ICF.

Exclusion Criteria:

1. Asymptomatic infection, mild or critical COVID-19.
2. SP02 \< 93% under high-flow oxygen inhalation, or receiving of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
3. Reinfected subjects with historical confirmed COVID-19, detectable by SARS-CoV-2 serological test (nasopharyngeal SARS-CoV-2 RNA levels or serum antibody).
4. May be transferred to another hospital, that is not one of the trial sites, within 72 hours.
5. Meets one of the following high-risk factors: a) Pre-existing cardiovascular (including uncontrolled hypertension: SBP≥ 160 mmHg and/or DBP≥ 100 mmHg) and cerebrovascular diseases, chronic lung diseases (chronic obstructive pulmonary disease (COPD), moderate to severe asthma), diabetes (HbA1c \> 9.0%), chronic liver diseases, chronic kidney diseases, malignancies or other complicated diseases. b) Pre-existing Immunosuppression (such as AIDS, long-term use of corticosteroids or other immunosuppressive drugs that lead to a weakened immune function). c) Obesity: body mass index ≥ 35. d) Heavy smokers: ≥20 cigarettes per day on average.
6. History of allergic to IVIG, other plasma proteins or blood products, history of selective IgA deficiency with presence of anti-IgA antibodies.
7. Vaccinated in last 8 weeks, such as influenza, poliomyelitis, measles, rubella, mumps and varicella virus vaccines.
8. May worsen and progress to critical COVID-19 rapidly.
9. Useage of other antiviral drugs to treat SARS-CoV-2 (except the basic treatment specified in the protocol) before randomization.
10. History of major surgery (defined as life-threatening surgery, requiring general anesthesia and causing severe bleeding, including bone and joint surgery on elbow, shoulder, hip, knee, ankle and spine) within 8 weeks before screening (including 8 weeks), or plan to surgery during the trial, which may bring unacceptable risks to the subjects, evaluation by investigators.
11. ALT or AST \> 2 times of the normal range upper limit, or Ccr \< 60 ml/min.
12. D-dimer increased significantly (\> 1 mg/L); History of thromboembolism or coagulation diseases in last 1 year, such as acute coronary syndrome, cerebrovascular syndrome, pulmonary or deep vein thrombosis, etc.
13. Positive of virues makers ( positive of HBsAg, HCV-Ab, or Treponema pallidum specific antibody).
14. History of organ transplantation (such as heart, lung, liver, kidney, etc.
15. Pregnant or lactating female.
16. Other subjects who are not suitable to participate in the trial considered by the investigator, such as potential compliance problems, can not complete all the examinations and evaluations according to the protocol, mental illness, obvious mental disorders; Incapacity or cognitive ability caused by other reasons.
17. History of participated in other investigate drugs or medical devices clinical trials in last 1 month before signing ICF.

Primary outcomes:
measure: Time to clinical improvement
timeFrame: within 28 days
Secondary outcomes:
measure: Changes of 7-point ordinal scale for COVID-19 clinical improvement
timeFrame: 7 days, 14 days, and 28 days
measure: COVID-19-Related Symptoms
timeFrame: 1 day, 3 days, 5 days, 7 days and 14 days
measure: Discharge Status
timeFrame: 7 days, 14 days, and 28 days
measure: Length of hospital stay
timeFrame: within 28 days
measure: All-cause Mortality
timeFrame: within 28 days
measure: Negativization rate of SARS-CoV-2 nucleic acid
timeFrame: within 72 hrs (24 hrs, 48 hrs, 72 hrs), 7 days, 14 days, and 28 days
measure: Changes of leukocyte count, lymphocyte count, C-reactive protein, IL-6 and SARS-CoV-2 nucleic acid (quantitative)
timeFrame: 1 day, 3 days, 5days, 7 days, 14 days
measure: Treatment in ICU
timeFrame: within 28 days
measure: SARS-CoV-2 Neutralizing Antibody Level
timeFrame: 1 day, 3 days, 7 days, and 28 days
measure: Glucocorticoid therapy
timeFrame: within 28 days
measure: Rate of worsening
timeFrame: within 28 days
measure: Finger oxygen saturation
timeFrame: 1 day, 3 days, 5 days, 7 days, 14 days, and 28 days
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: Al Rahba Hospital
Study officials:
affiliation: Sheikh Khalifa Medical City, SEHA
name: Nawal Al Kaabi, MBBA
role: PRINCIPAL_INVESTIGATOR
References: