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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
Sponsor:
Information provided by (Responsible Party):
Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd

Brief Summary:
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

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Meplazumab for Injection Drug: Sterile normal saline (0.9%) Phase 2 Phase 3

Detailed Description:
  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: 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.

  5. Treatment Groups and Duration:

Study duration for each subject will be 84±7 days from randomization in each stage.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 456 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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

Arm Intervention/treatment
Experimental: Meplzaumb
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%)




Primary Outcome Measures :
  1. 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.


  2. Response rate [ Time Frame: Day 29 ]

    As defined by a sustained improvement of 2 points on a 6-point ordinal scale

    1. 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.
    2. 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.

  3. Mortality [ Time Frame: Day 29 ]
    Analyze using the same Cochran-Mantel-Haenszel (CMH) test and logistic regression.

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Weight in kilogram [ Time Frame: Day1 and Day8 ]
    Weight will be obtained on days when investigator drug is administered

  4. Blood pressure in mmHg [ Time Frame: Day 1 through Day14, Day 15 and 29 ]
    Blood pressure will be obtained

  5. saturation in percentage [ Time Frame: Day 1 through Day14, Day 15 and 29 ]
    finger oxygen saturation will be obtained

  6. Temperature in ℃ [ Time Frame: Day 1 through Day14, Day 15 and 29 ]
    Temperature will be obtained

  7. 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

  8. 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

  9. 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

  10. 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:

    1. Anemia that is not due to another obvious cause
    2. Increased reticulocyte count that is not explained by an obvious cause
    3. Signs of RBC destruction, such as increased lactate dehydrogenase (LDH), low haptoglobin ≤25 mg/dL, increased unconjugated bilirubin.

  11. Mortality [ Time Frame: Day 15 and 57 ]
    Use the same Cochran-Mantel-Haenszel (CMH) test and logistic regression model as in the primary endpoint.

  12. 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:

    1. Not hospitalized
    2. Hospitalized, not requiring supplemental oxygen



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

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


Contacts
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Contact: Xiaochun Chen 86-519-68889888 cxc@pmbp.cn
Contact: Shuangshuang Liu 86-519-68889888 lss@pmbp.cn

Sponsors and Collaborators
Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
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Responsible Party: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
ClinicalTrials.gov Identifier: NCT04586153    
Other Study ID Numbers: MPZ-II-02
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No