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JBT-101 in Systemic Lupus Erythematosus (SLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03093402
Recruitment Status : Recruiting
First Posted : March 28, 2017
Last Update Posted : March 10, 2020
Sponsor:
Collaborators:
Corbus Pharmaceuticals Inc.
Autoimmunity Centers of Excellence
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE February 21, 2017
First Posted Date  ICMJE March 28, 2017
Last Update Posted Date March 10, 2020
Actual Study Start Date  ICMJE December 21, 2017
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2017)
Change from Baseline in the 7-Day Average of the Maximum Daily NRS-Pain Score at Day 84 [ Time Frame: Baseline (Day 1), Day 84 (Visit 5, Last Day of Treatment) ]
The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. Participants will be asked to report their maximum daily pain using the NRS-Pain. Participants will call into an interactive voice response e diary system (IVRS) and record the number that best reflects their maximum amount of pain experienced in the last 24 hours. Participants will be asked to call at the same time each day, preferably before bedtime. Baseline: Pre-treatment; Day 84: Last Day (Visit 5) of a 12-week course of assigned treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2017)
  • Change from Baseline in the 7-day Average of the Maximum NRS-Pain Score Prior to Study Visits [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    The numeric rating scale for pain (NRS-Pain) consists of an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). A rating of 1-3 is considered mild pain; 4-6, moderate pain; and 7-10, severe pain. The percent change in the 7-day average of the maximum NRS-Pain scores prior to study Visit 1 (Baseline), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84) and Visit 6 (Day 112) will be assessed.
  • Change from Baseline in Active Lupus Musculoskeletal Disease Activity - BILAG-2004 [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in active Systemic Lupus Erythematosus (SLE) musculoskeletal disease activity over time will be assessed based on the musculoskeletal domain of the British Isles Lupus Activity Group (BILAG) 2004.
  • Change from Baseline in Lupus Disease Activity - SELENA-SLEDAI Score [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in active lupus activity over time will be assessed based on the SELENA SLEDAI score. The Safety of Estrogen in Lupus National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is a validated tool for assessing SLE disease activity.
  • Change from Baseline in Lupus Disease Activity - Total BILAG-2004 Score [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in active lupus over time will be evaluated based on the total BILAG-2004 score. The BILAG-2004* is a validated index for assessing SLE disease activity. The BILAG-2004 includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems. * BILAG-2004: British Isles Lupus Assessment Group 2004.
  • Change from Baseline in Lupus Disease Activity -Physician's Global Assessment (PGA) Score [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in active lupus over time will be based on the total PGA score.
  • Change from Baseline in Lupus Disease Activity- Patient Global Assessment Score [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in active lupus over time will be based on the total Patient Global Assessment score.
  • Change from Baseline in State of Health- PROMIS-29 Short Form Score [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Short Form (Version 2.0) will be used to assess trends over time in this state of health measure.
  • Change from Baseline in State of Health -PROMIS-Applied Cognition General Concerns Score [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112)] ]
    The Patient-Reported Outcomes Measurement Information System (PROMIS) Applied Cognition General Concerns (Version 1.0) scale will be used to assess trends over time in this health measure.
  • Treatment Satisfaction After Twelve Weeks of Assigned Treatment [ Time Frame: Visit 5 (Day 84 - Last Day of Treatment) ]
    At the end of 12 weeks of treatment, the participant and their physician will complete separately a survey asking what treatment assignment they believe they received (e.g., JBT-101, placebo, or cannot tell), whether the participant received benefit from their assigned treatment and whether the participant or their physician would choose the treatment received.
  • Number of Grade 3 or Higher Treatment-emergent Adverse Events (TEAS) During Treatment Phase of Study [ Time Frame: Day 1 after initiation of study intervention through Day 112 ]
    The number of TEAS will be identified by monitoring participant-reported AEs, vital signs, medical history, physical exams, blood and urine safety tests, 12-lead electrocardiograms, and the Addiction Research Center Inventory-Marijuana (ARCI-M). TEAS are defined as AEs that, in the opinion of the blinded/masked site investigator, are " possibly", "probably" or "definitely" related to the assigned study treatment. Unless noted otherwise, grading will be defined by the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
  • Change from Baseline in Disease Activity Using the SLE Responder Index (SRI) [ Time Frame: (Baseline, Day 1-prior to treatment initiation), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in Systemic Lupus Erythematosus (SLE) disease activity over time will be assessed using the SRI. The SRI is a validated SLE disease activity instrument used to detect clinically meaningful improvement of disease in SLE clinical trials. The SRI is a composite instrument comprised of the SELENA-SLE Disease Activity Index [SELENA-SLEDAI], Physician Global Assessment (PGA) and British Isles Lupus Assessment Group (BILAG) 2004.
  • SLE Disease Flares by Severity Using the SELENA-SLEDAI Flare Index (SFI) [ Time Frame: Baseline, (Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    The SFI instrument will be used to define disease flare(s) and severity over time.
  • Change from Baseline in Active Musculoskeletal Disease Defined by the Presence or Absence of Arthritis Using the SELENA-SLEDAI [ Time Frame: Baseline (Day 1-prior to treatment initiation), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    The validated SELENA-SLEDAI* tool will be used to assess trends over time in active musculoskeletal disease activity based on presence or absence of arthritis. * Safety of Estrogens in Lupus Erythematosus:National Assessment Version of the Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI]
  • Change from Baseline in Swollen Joint Count [ Time Frame: Baseline, (Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in active musculoskeletal disease activity over time will be assessed using the physician-assessed swollen joint count assessments.
  • Change from Baseline in Tender Joint Count [ Time Frame: Baseline, (Day 1), Visit 3 (Day 28), Visit 4 (Day 56), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in active musculoskeletal disease activity over time will be assessed using the physician-assessed tender joint count assessments.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 22, 2017)
  • Change from Baseline in Disease Activity Using C-Reactive Protein [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Serum C-reactive protein (CRP) will be used as a biomarker of active SLE disease-associated inflammation.
  • Change in Serum Pro-Inflammatory Cytokine Levels [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in pro-inflammatory serum cytokines over time (e.g., IFN alpha, IFN gamma, IL-6, TNF alpha, IL-1beta, etc.) will be assessed by ELISA assay.
  • Change in pro-inflammatory cytokine expression in peripheral blood mononuclear cells (PBMCs) pre- and post-TLR stimulation [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in pro-inflammatory cytokines over time will be evaluated by in vitro assays prior to and after toll-like receptor (TLR) stimulation using CpG and Gardiquimod.
  • Percentage of Participants with Type 1 IFN Gene Expression Signature [ Time Frame: Visit 1 (Baseline, Day 1), Visit 3 (Day 28), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    Trends in the presence of Type 1 interferon (IFN) alpha gene expression over time using total RNA from whole blood will be evaluated.
  • Change from Baseline in Plasma Metabolipidomic Profile [ Time Frame: Visit 1 (Baseline, Day 1), Visit 2 (Day 14), Visit 3 (Day 28) and Visit 5 (Day 84 - Last Day of Treatment) ]
    Trends in levels of bioactive lipids (e.g., lipoxin A4, anti- and pro-inflammatory eicosanoids, etc.) in plasma over time will be assessed.
  • Change from Baseline in JBT-101 Plasma Concentrations [ Time Frame: Visit 1 (Baseline, Day 1), Visit 2 (Day 14), Visit 3 (Day 28) and Visit 5 (Day 84 - Last Day of Treatment) ]
    Trends in JBT-101 plasma concentrations over time will be assessed.
  • Change from Baseline in JBT-101 Metabolites [ Time Frame: Visit 1 (Baseline, Day 1), Visit 2 (Day 14), Visit 3 (Day 28) and Visit 5 (Day 84 - Last Day of Treatment) ]
    Trends in the presence of JBT-101 metabolites over time will be assessed.
  • EXPLORATORY: Change from Baseline in Participant Fibromyalgia Symptom Score [ Time Frame: Visit 1 (Baseline, Day 1), Visit 5 (Day 84 - Last Day of Treatment) and Visit 6 (Day 112) ]
    The presence and severity of fibromyalgia will be assessed over time using the Fibromyalgia Symptom Scale instrument.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE JBT-101 in Systemic Lupus Erythematosus (SLE)
Official Title  ICMJE A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter Study to Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic Lupus Erythematosus (ALE09)
Brief Summary

The objective of this study is to evaluate the efficacy, safety, and tolerability of JBT-101 (also known as lenabasum) in systemic lupus erythematosus (SLE).

  • One hundred adults with active joint disease and at least moderate pain will be enrolled in this study to evaluate treatment of their systemic lupus erythematosus (SLE) with JBT-101. JBT-101 is a synthetic endocannabinoid receptor type 2 (CB2) agonist and an activator of the body's normal processes, to resolve innate immune responses without immunosuppression.
  • Participants will receive 2 doses of JBT-101 by mouth (three groups of varying doses) or, placebo, for 84 days and will continue to be followed for an additional 28 days. Participant visits to assess endpoints occur on Day 1, then every 2 weeks twice, then every 4 weeks three times, for a total of six visits.
  • The change in maximum daily pain Numerical Rating Scale (NRS) score from Baseline (Visit 1) will be assessed at every visit.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Systemic Lupus Erythematosus
  • SLE
  • Lupus
Intervention  ICMJE
  • Drug: JBT-101
    Participants will self-administer JBT-101 by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.
    Other Names:
    • lenabasum
    • anabasum
    • resunab
    • ajulemic acid
    • CT-3
    • IP751
    • CPL7075
  • Drug: Placebo
    Participants will self-administer JBT-101 placebo by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.
    Other Names:
    • JBT-101 placebo
    • lenabasum placebo
Study Arms  ICMJE
  • Experimental: JBT-101: 5 mg Twice Daily
    Eligible subjects will receive assigned study treatment of JBT-101 5 mg administered twice daily.
    Intervention: Drug: JBT-101
  • Experimental: JBT-101: 20 mg & Placebo
    Eligible subjects will receive assigned study treatment of JBT-101 20 mg (A.M. Study Product) and 20 mg Placebo (P.M. Study Product).
    Interventions:
    • Drug: JBT-101
    • Drug: Placebo
  • Experimental: JBT-101: 20 mg Twice Daily
    Eligible subjects will receive assigned study treatment of JBT-101 20 mg (A.M. Study Product) and JBT-101 20 mg (P.M. Study Product).
    Intervention: Drug: JBT-101
  • Placebo Comparator: Placebo + Placebo
    Eligible subjects will receive assigned study treatment of Placebo (A.M.) and Placebo (P.M.) for (JBT-101).
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 22, 2017)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Fulfills the updated American College of Rheumatology (ACR) 1982 Revised Criteria for the Classification of Systemic Lupus Erythematosus;
  • At least 3 months of treatment with an anti-malarial drug such as hydroxychloroquine or a history of intolerance, contraindication, or unwillingness to take an anti-malarial drug;
  • Meets the Safety of Estrogen in Lupus: National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) definition of arthritis (Petri et al., 1999) or mild/moderate arthritis or tendonitis scored as a BILAG B on the updated BILAG 2004;
  • Seven-day average of maximum of daily pain Numerical Rating Scale (NRS) scores ≥ 4 out of 10;
  • Overlap with polymyositis, systemic sclerosis, Sjögren's syndrome, or rheumatoid arthritis is allowed, if, in the site investigator's judgment, the predominant clinical features are those of Systemic Lupus Erythematosus (SLE);
  • Not expected by the site investigator to require a change in potential disease- modifying treatments for SLE from Screening through Visit 6 (Day 112);
  • Willing to not start nor stop any Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or potential disease-modifying medications or supplements for SLE from Screening through Visit 6 (Day 112), unless a change is recommended by the site investigator or other treating physicians;
  • Willing not to use any legal or illegal cannabinoids, including Food and Drug Administration (FDA)-approved cannabinoids or cannabinoid-mimic drugs, or any illegal substance of abuse from Screening through Visit 6 (Day 112);
  • If a woman of child-bearing potential, willing to use one of the highly effective (failure rate < 1% per year) birth control method from Screening through Visit 6 (Day 112) or for 28 ± 3 days after the last dose of study product; and
  • Willing to follow instructions, complete study procedures and attend study visits as required by this protocol.

Exclusion Criteria:

  • Severe or unstable Systemic lupus erythematosus (SLE), such as any one of the following:

    • A British Isles Lupus Activity Group (BILAG) A score in one or more BILAG domains at Screening;
    • Treatment with any intraarticular, intravenous, or intramuscular systemic corticosteroids within 14 days of Screening;
    • Treatment with oral prednisone > 10 mg per day or > 20 mg every other day (or equivalent dose of another corticosteroid) within 14 days of Screening;
    • Increased dose of systemic corticosteroids in the 14 days prior to Screening;
    • Treatment with cyclophosphamide or anti-TNFalpha biologic agents within 3 months before Visit 1 (Day 1);
    • Treatment with B cell-depleting monoclonal antibodies (rituximab, Ocrelizumab, anti-CD22) within 6 months before Visit 1 (Day 1);
    • Treatment with methotrexate, mycophenolate, azathioprine, leflunomide, cyclosporine, belimumab, tacrolimus, or any other immunosuppressive agent not included in 2b.-d. above, when the dose of that immunosuppressive agent has increased within 3 months before Visit 1. Concurrent treatment with any of these medications is allowed as long as the doses have been stable for at least 3 months before Visit 1 (Day 1); or
    • Actively listed on an organ transplantation list or have received an organ transplant other than a corneal transplant.
  • Significant diseases or conditions other than SLE that may influence response to the study product or safety, such as:

    • Active bacterial or viral infection requiring systemic antibiotic or anti-viral treatment within 14 days before Visit 1 (Day 1);
    • Acute or chronic hepatitis B or C infection;
    • Human immunodeficiency infection (HIV);
    • History of active tuberculosis or positive tuberculosis skin or blood test without: 1) completing a course of appropriate treatment; or ) having received at least one month of appropriate treatment prior to Visit 1 (Day 1) and continuing to receive appropriate treatment during the study;
    • No elective surgery should be planned from Visit 1 (Day 1) through Visit 6 (Day 112); or
    • A history of cancer except basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy greater than one year before Visit 1 (Day 1).
    • Significant heart disease as defined by:

      • Uncontrollable congestive heart failure, unstable angina, unstable atherosclerotic cardiovascular disease, significant arrhythmia requiring chronic therapy, pulmonary arterial hypertension with dyspnea, disability rated as New York heart Association Grade III or higher, severe systemic hypertension or severe peripheral vascular disease;
      • Marked baseline prolongation of QT/QTc interval (i.e. repeated demonstration of a QTc interval ≥ 450 msec for males and ≥470 msec for females);
      • History of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT/QTc syndrome); or
      • Clinically significant confirmed abnormality, as determined by the site investigator or qualified designee, on 12-lead Electrocardiogram (ECG) at Screening or Visit 1 (Day 1) before dosing.
  • History of chronic pain requiring treatment with narcotic analgesia for more than 14 days total within 6 months of baseline. This does not include self-limited pain associated with identifiable events such as surgery;
  • Current evidence of alcohol abuse (defined as 4 or more drinks per day on at least 4 days of the week) or history of abuse of illegal and/or legally prescribed drugs such as barbiturates, benzodiazepines, amphetamines, cocaine, or opioids during the 1 year prior to Screening;
  • Currently pregnant, breast-feeding, or lactating;
  • Any investigational agent within 30 days or five therapeutic half-lives of that agent whichever is longer, before Visit 1 (Day 1);
  • Any of the following values for laboratory tests at Screening:

    • A positive pregnancy test (also at Visit 1);
    • A newly positive QuantiFERON(R) blood test for tuberculosis, without: 1) completing a course of appropriate treatment; or ) having received at least one month of appropriate treatment prior to Visit 1 and continuing to receive appropriate treatment during the study. If the subject has a previous documented positive tuberculosis skin, then this testing does not need to be repeated. If the subject has a documented negative test result within the last year, testing does not need to be repeated, at the discretion of the site investigator.
    • Hemoglobin < 8 g/dL;
    • Neutrophils < 1.0 x 10^9/L;
    • Platelets < 75 x 10^9/L;
    • Estimated Glomerular Filtration Rate (eGFR) < 50 ml/min according to Cockcroft-Gault equation;
    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase > 2.0 x upper limit of normal; or
    • Total bilirubin ≥ 1.5 x upper limit of normal.
  • Any other conditions that, in the opinion of the site investigator, are clinically significant and may put the subject at greater safety risk, influence response to study product, or interfere with study assessments. When in doubt, the site investigator or qualified designee should discuss the situation with the Protocol Chairs.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03093402
Other Study ID Numbers  ICMJE DAIT ALE09
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The plan is to share data in ImmPort [https://immport.niaid.nih.gov/ ], a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts, upon completion of the study.
Time Frame: After completion of the study.
Access Criteria: Data is available to the public once Individual Participant-Level data is posted to ImmPort.
URL: http://www.immport.org/
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • Corbus Pharmaceuticals Inc.
  • Autoimmunity Centers of Excellence
Investigators  ICMJE
Study Chair: Meggan Mackay, M.D., M.S. The Feinstein Institute for Medical Research
Study Chair: Robert B. Zurier, M.D. The Feinstein Institute for Medical Research
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP