This phase2/3 study will be conducted to evaluate the safety and efficacy of Meplazumab in addition to Standard of Care for the treatment of Corona Virus Disease(COVID) 19 in hospitalized adults
1. Rationale:
Meplazumab is a humanized anti-CD147 immunoglobulin 2 (IgG2) monoclonal antibody which
is expected to block the binding of the severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) spike protein to the human host-cell-expressed CD147, thereby blocking
entry of SARS-CoV-2 into human tissue. This expectation is based on in vitro functional
studies using Vero E6 cells infected with SARS-CoV-2 that demonstrated effective
meplazumab mediated virus gene copy number inhibition upwards of 90% as evaluated by
quantitative polymerase chain reaction. Meplazumab may also inhibit COVID-19 associated
cytokine storm syndrome based on inhibition of the pro inflammatory factor Cyclophilin A
host-cell CD147 interaction.
2. Overall Design:
This is a multicenter, seamless, randomized, third-party-blind, study to evaluate the
safety and efficacy of meplazumab for the treatment of COVID 19 in hospitalized adults
(≥18 years). Neither the subject nor the investigator shall be aware of the study drug
identity, as the study drug is dispensed by a third party (eg, a pharmacist or nurse).
Enrollment of subjects will be stopped once the total number of planned subjects have
completed the Stage 1 Day 29 visit procedures. Once the interim analysis of Stage 1
study data is complete and the Independent Data Monitoring Committee (IDMC) has
recommended the meplazumab dose that is safe and effective to carry forward into Stage
2, the study will resume subject enrollment. A summary of the key Stage 1 interim
analysis results will be sent to the relevant Health Authorities involved, if requested.
3. Number of Investigators and Study Centers:
There will be 15 to 20 Investigators, at 12 to 20 study centers globally, participating
in this study.
4. Number of Subjects:
Subjects will be screened 1 day before randomization. Stage 1: Approximately 168
subjects will be randomized and allocated 1:1:1:1 (42:42:42:42) to receive meplazumab
low dose, meplazumab medium dose, meplazumab high dose, or control. An interim analysis
will be conducted to select the optimal dose of meplazumab compared with the control
group based on response rates of clinical improvement at Day 29.
Stage 2: 276 more subjects will be randomized and allocated 1:1 (138:138) to receive
0.2mg/kg meplazumab or control. At interim analysis, primary endpoint, sample size
calculation for Stage 2 will be re evaluated based on the observed outcomes at Stage 1
and will be capped at 300 subjects total.
5. Treatment Groups and Duration:
Study duration for each subject will be 84±7 days from randomization in each stage.
Drug: Meplazumab for Injection
humanized antibody target CD147
Drug: Sterile normal saline (0.9%)
Sterile normal saline (0.9%)
Inclusion Criteria:
- Adults (≥18 years) with laboratory-confirmed SARS CoV 2 infection as determined by PCR
or other commercial or public health assay, which is FDA cleared or approved for
emergency use (test results must be obtained within 72 hours of Day
- A score of Grade 3 (hospitalized, requiring supplemental oxygen) or Grade 4
(hospitalized, on non-invasive ventilation or high flow oxygen devices) on the 6-point
ordinal scale.
- Willingness and ability to comply with study-related procedures and assessments.
- Ability to provide informed consent signed by study subject or legally authorized
representative.
- Male and/or female
a)Male subjects:
- A male subject must agree to use contraception as detailed in Appendix 12.3 of this
protocol during the treatment period and for at least 6 months, corresponding to time
needed to eliminate study treatment for both genotoxic and teratogenic study
treatments, after the last dose of study treatment.
b)Female subjects:
- A female subject is eligible to participate if she is not pregnant (see Appendix
12.3), not planning to get pregnant in the next 6 months, not breastfeeding, and at
least 1 of the following conditions applies:
i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 12.3. OR ii) A
WOCBP who agrees to follow the contraceptive guidance in Appendix 12.3 during the
treatment period and for at least 130 days, (5 terminal half lives and, for genotoxic
products, an additional 30 days, corresponding to time needed to eliminate study
treatment plus 30 days for study treatments with genotoxic potential) after the last
dose of study treatment.
Exclusion Criteria:
- Any physical examination findings, laboratory abnormality, and/or history of any
illness, that in the study Investigator's judgment, could jeopardize the safety of the
subject by their participation in the study.
- Subjects with evidence of critical COVID 19 illness, defined by at least 1 of the
following: respiratory failure; shock (defined by systolic blood pressure <90 mm Hg,
or diastolic blood pressure <60 mm Hg, or requiring vasopressors); or multi-organ
dysfunction/failure.
- Subjects requiring extracorporeal membrane oxygenation (ECMO).
- Stage 4 severe chronic kidney disease or requiring dialysis (ie, estimated glomerular
filtration rate(eGFR) mL/min/1.73 m2 < 30).
- Pregnant or breast feeding.
- Anticipated transfer to another hospital which is not a study site within 72 hours.
- Allergy to any study medication.
- Use of anticancer, antitransplant rejection, or immunomodulatory biological drug or
kinase inhibitor (eg, tocilizumab, sarilumab) or Janus kinase inhibitors (within 30
days of enrollment or 5 times the half-life [whichever is longer]).
- Chronic glucocorticosteroid use equivalent to daily oral prednisone >10 mg per day (10
mg oral prednisone every other day is allowed).
- Live (live-attenuated) vaccines are not permitted within 2 weeks prior to
randomization or during the study treatment and safety follow-up periods.
- Subjects participating in another clinical study. There will be a need for washout
with 5 half lives depending on the study treatment or 30 days since any previous
study, whichever is longer.
- Total bilirubin (TBL) >2 × upper limit of normal (ULN), or alanine aminotransferase
(ALT) >5 × ULN, or aspartate aminotransferase (AST) >5 × ULN, or alkaline phosphatase
>5 × ULN.
- Platelet <50×109/L, or hemoglobin <60g/L.
- Glomerular filtration rate <30 milliliter(mL)/min/1.73 m2, or serum creatinine
increased by 0.5 mg/dL within 7 days, or oliguria (<400 mL/24 hour), or anuria (<100
mL/24 hour).
- Any physical examination findings, laboratory abnormality, and/or history of any
illness, that in the study Investigator's judgment, could jeopardize the safety of the
subject by their participation in the study.
Pesquisare Saúde
Santo André, Sao Paulo, Brazil
Investigator: Wladmir Saporito
Contact: 551144322953
Xiaochun Chen
86-519-68889888
cxc@pmbp.cn
Shuangshuang Liu
86-519-68889888
lss@pmbp.cn