Study to Assess the Effect of Meplazumab on COVID-19
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|ClinicalTrials.gov Identifier: NCT04586153|
Recruitment Status : Not yet recruiting
First Posted : October 14, 2020
Last Update Posted : November 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Drug: Meplazumab for Injection Drug: Sterile normal saline (0.9%)||Phase 2 Phase 3|
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.
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.
Number of Investigators and Study Centers:
There will be 15 to 20 Investigators, at 12 to 20 study centers globally, participating in this study.
Number of Subjects:
Subjects will be screened 1 day before randomization. Stage 1: 216 subjects will be randomized and allocated 1:1:1:1 (54:54:54:54) 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: 240 more subjects will be randomized and allocated 2:1 (160:80) to receive either the optimal meplazumab dose determined after Stage 1, 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.
- Treatment Groups and Duration:
Study duration for each subject will be 84±7 days from randomization in each stage.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||456 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Multicenter, Seamless, Randomized, Third-Party-Blind, Clinical Trial to Evaluate the Safety and Efficacy of Meplazumab in Addition to Standard of Care for the Treatment of COVID-19 in Hospitalized Adults|
|Estimated Study Start Date :||December 30, 2020|
|Estimated Primary Completion Date :||April 28, 2021|
|Estimated Study Completion Date :||September 30, 2021|
This arm is combined with 3 groups, low dose, middle dose, and high dose. Low dose group: First dose: 0.12 mg/kg - Day 1; second dose: control - Day 8 Middle dose group: First dose: 0.2 mg/kg - Day 1; second dose: 0.2 mg/kg - Day 8 High dose group: First dose: 0.3 mg/kg - Day 1; second dose: 0.3 mg/kg - Day 8
Drug: Meplazumab for Injection
humanized antibody target CD147
Placebo Comparator: Placebo
First dose: control - Day 1; second dose: control - Day 8
Drug: Sterile normal saline (0.9%)
Sterile normal saline (0.9%)
- Time to sustained clinical improvement [ Time Frame: Day 1 through Day 29 ]
Of at least 2 points (from randomization) on a 6-point ordinal scale, (where sustained improvement is improvement without subsequent worsening), or live discharge from the hospital, whichever comes first.
The time to event endpoints, including time to sustained clinical improvement by Day 29 from treatment start date will be compared between the treatment arms stratifying for age group (age <65 years versus ≥65 years) and baseline severity grade, with death handled as competing risk, and the equivalence of cumulative incidence curve will be tested using the Gray's test at the 2-sided alpha level of 0.05. The unstratified cumulative incidence curve will be plotted for each treatment arm. Additionally, Cox regression model will be used to model the sub-distribution hazard ratio (HR) between treatment arms under the Fine and Gray's competing risk framework, with death handed as competing risk; the HR and its 95% Confidence Interval(CI) will be reported.
- Response rate [ Time Frame: Day 29 ]
As defined by a sustained improvement of 2 points on a 6-point ordinal scale
- Analysis of response rate Conduct between the selected dose group and control using Cochran-Mantel-Haenszel (CMH) statistic, stratifying for age group (age <65 years versus ≥65 years), and baseline severity grade, and additional stratification factors if any as determined after evaluation of Stage 1 data.
- Sensitivity analyses on the response rate Fit the response variable using logistic regression, including treatment, baseline, baseline and treatment interaction, age group (age <65 years versus ≥65 years), and age group and treatment interaction as fixed effects.
- Mortality [ Time Frame: Day 29 ]Analyze using the same Cochran-Mantel-Haenszel (CMH) test and logistic regression.
- Proportion of subjects alive and discharged without supplemental oxygen [ Time Frame: Day 29 ]Analyze using the same Cochran-Mantel-Haenszel (CMH) test and logistic regression.
- Response rate [ Time Frame: Day 2,8 and 15 ]as defined by an improvement of 2 points on a 6-point ordinal scale. Use the same Cochran-Mantel-Haenszel (CMH) test and logistic regression model as in the primary endpoint.
- Proportion of subjects alive and discharge without supplemental oxygen [ Time Frame: Day 15 and 57 ]Use the same Cochran-Mantel-Haenszel (CMH) test and logistic regression model as in the primary endpoint.
- Weight in kilogram [ Time Frame: Day1 and Day8 ]Weight will be obtained on days when investigator drug is administered
- Blood pressure in mmHg [ Time Frame: Day 1 through Day14, Day 15 and 29 ]Blood pressure will be obtained
- saturation in percentage [ Time Frame: Day 1 through Day14, Day 15 and 29 ]finger oxygen saturation will be obtained
- Temperature in ℃ [ Time Frame: Day 1 through Day14, Day 15 and 29 ]Temperature will be obtained
- 12-lead electrocardiograms (ECGs) [ Time Frame: Day 1 and 29 ]Using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals
- Virologic load [ Time Frame: Day 1, 3, 5, 8 and 9 or 10, 29 and 57 ]quantitative Polymerase Chain Reaction(PCR) for COVID 19 in nasopharyngeal swab
- Antidrug antibody (ADA) titers [ Time Frame: Day 1, 29, 57 and 84 ]Collection of blood samples for immunogenicity assessments # using validation Anti-body testing assay to test the presence of antidrug antibody
- Adverse events (AEs) of special interest [ Time Frame: 84 days (from first dose to the end of study) ]
disease-related secondary infection complications, hemolysis, Grade 4 (Common Terminology Criteria for Adverse Events V5 [CTCAE]) neutropenia and lymphopenia, and anaphylactic reactions defined by Clinical Criteria for Diagnosing Anaphylaxis(0); 20% decline in SpO2 between start and end of 1-hr study treatment infusion; ALT or AST >3 x ULN AND TBL >2 x ULN; Evidence of red blood cell (RBC) hemolysis as defined by 2 of the following 3 findings:
- Anemia that is not due to another obvious cause
- Increased reticulocyte count that is not explained by an obvious cause
- Signs of RBC destruction, such as increased lactate dehydrogenase (LDH), low haptoglobin ≤25 mg/dL, increased unconjugated bilirubin.
- Mortality [ Time Frame: Day 15 and 57 ]Use the same Cochran-Mantel-Haenszel (CMH) test and logistic regression model as in the primary endpoint.
- Time to sustained recovery [ Time Frame: Day 1 through Day 29 ]
as defined by first day on which 1 of the following 2 categories is achieved using the 6-point ordinal scale：
- Not hospitalized
- Hospitalized, not requiring supplemental oxygen
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04586153
|Contact: Xiaochun Chenfirstname.lastname@example.org|
|Contact: Shuangshuang Liuemail@example.com|