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CompletedNCT04379271Updated Nov 13, 2024Results posted

A Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator's Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19 (COVID-19)

A Phase 2/3 interventional study of IMU-838 and Placebo in COVID-19, sponsored by Immunic AG. Completed at 4 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-13.

Sponsored by Immunic AG · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
234
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

At present there is no approved drug treatment for Covid-19. In this study we plan to investigate if an experimental drug called IMU-838 (vidofludimus calcium) can improve your symptoms, prevent worsening that would initiate further treatments such as ventilation, and can lower your virus number if given in addition to your doctor's choice of standard therapy. We will also test if IMU-838 has any side effects and measure the level of IMU 838 in your blood.

Experimental drug means that it is not yet authorized for marketing in your country. To date approximately 600 individuals have received IMU-838 (or a drug similar to IMU-838 that contains the same active substance as IMU-838) in research studies.

Read the detailed description

The trial consists of a Phase 2 proof-of-concept phase (Part 1) with the option to extend enrollment (without interruption) to Phase 3 (Expansion Phase, Part 2).

This trial is a multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to evaluate the safety and efficacy of IMU-838 as addition to investigator's choice of SoC treatment in patients with COVID-19. Eligible patients will be centrally randomized 1:1 to twice-daily (BID) oral 22.5 mg IMU-838 (45 mg/day + SoC) or placebo (+ SoC). Randomization will be stratified by age (\< or >=65 years) and antiviral therapy (no antivirals, Hydroxychloroquine and Chloroquine, all other antivirals).

Adaptive sequential trial design and overall trial design

The trial uses an adaptive sequential design. An IDMC will review unblinded data and provide the Sponsor with recommendations regarding modifications of sample size and trial conduct.

A 1st interim analysis (IA1) will be performed after approximately 200 patients have completed the trial (either as scheduled or prematurely), while enrollment continues. If no activity of IMU 838 is observed by the IDMC in this IA, further patient enrollment will be stopped, and a final analysis of Part 1 will be performed (FA1). It is expected that the final analysis of Part 1 will include approximately 230 patients. If the IA1 results indicate activity of IMU-838 in COVID-19, the trial may be extended to Part 2 with a revised sample size derived by the IDMC based on IA1 results and with possible other trial adjustments. If the trial is extended into Part 2, a 2nd IA (IA2) is planned after approximately two-thirds of patients (based on the overall global sample size [Part 1 and Part 2 combined]) have been enrolled to potentially adjust sample size and other trial features if needed. The final analysis of the trial (FA2) will then be done after all patients have completed Part 2.

In addition, an early interim safety analysis will be performed and evaluated by the IDMC after 30 patients have been enrolled to assess unblinded safety data. Further safety analyses can be initiated at any time by the IDMC or Sponsor when new safety signals are identified within this or other trials of IMU-838.

Screening

Patients can be screened for a maximum of 2 days (from Day -2 to Day 0) and eligible patients will be randomized on Day 0 and treated with IMP + SoC for 14 days. It is encouraged to screen potential participants immediately at the day of hospitalization (including informed consent, assessment of inclusion/exclusion criteria, screening laboratory tests all done locally, assessment of clinical and blood gas criteria) and randomize patients on the same day (Day 0). To assess eligibility criteria, existing local laboratory values obtained within 48 hours of randomization can also be used, except for testing of positive status of SARS-CoV-2 infection where a 4-day window is allowed.

IMP administration should start as quickly as possible after randomization and first IMP intended to be given in the evening of the screening day (Day 0).

Blinded Treatment period (Day 0 to Day 13) and Day 14 (end-of-treatment)

The first dose of IMP (2 tablets) should always be given on Day 0 (allowed range for first dose: 12:00 noon on Day 0 to 02:00 a.m.). All further IMP doses are 1 tablet each in the morning and evening. Information about the status and patient care are continuously obtained and documented once or twice daily.

After the last IMP dose in the evening of Day 13, the end-of-treatment assessments will be done on Day 14. Blood sampling for IMU-838 trough values must be performed in the morning around the time the morning dose was usually taken by the respective patient. Patients may then continue to receive SoC without any further restrictions on concomitant medications as during the 14-day BT period .

Day 28 Visit (EoS)

The patient should return for the final trial visit on Day 28 (EoS). If IMP is prematurely discontinued for any reason, the EoS visit should always be conducted on Day 28 and no earlier EoS should be performed. If patients withdraw from IMP prematurely, they should be encouraged to allow the EoS visit as part of the follow-up. If the patient dies during the trial, the investigator should indicate that this visit was not performed. However, even if no EoS visit was performed, information about patient status should be reported on the EoS page in the case report form. If the patient refuses any EoS visit or the patient is lost to follow-up, it is permissive in this trial that the investigator contacts the patient, the family of the patient or the referring physician by phone or email to obtain status of life information, or is able to search in registers or publicly available information for such status of life information.

02

Conditions studied

  • COVID-19

Browse trials for

03

In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 234 is above the median of 100 across 4,098 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

Immunic AG is the lead sponsor of 7 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or female patients at least 18 years old (may be extended to include also children 12 years or older after the 1st interim analysis)

  2. Admitted to the hospital or other medical in-patient treatment facility for treatment of COVID-19 The hospitalization needs to be for medical reasons (treatment of COVID-19 disease) and cannot be for social reasons or due to housing insecurity.

    For US sites only: If the investigator would commonly hospitalize the patient but for healthcare resource reasons decides to treat the patient in a specially designed out-patient setting, then such patients are also allowed to enter the trial (please note that in this case the patient would be counted as clinical status category 3). The investigator then must assure that the patient has at least a twice daily assessment by qualified trial personnel and all laboratory assessments can be adequately performed as per protocol. The Sponsor reserves the right to discontinue this option via administrative letter if such assurances cannot be met by any site.

  3. SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) test in a nasopharyngeal, oropharyngeal or respiratory sample at ≤4 days before randomization

  4. Moderate COVID-19 disease defined as fulfilling clinical status category 3 or 4 on the WHO 9-point ordinal scale [21]:

    • Category 3: Hospitalized (see note above for US only), virus-positive, no oxygen therapy with the following conditions:
    • The hospitalization needs to be for medical reasons (treatment of COVID-19 disease) and cannot be for social reasons or due to housing insecurity
    • Category 4: Hospitalized, virus-positive, oxygen by mask or nasal prongs (excluding high-flow oxygen therapy) with the following conditions:
    • Peripheral capillary oxyhemoglobin saturation (SpO2) >92% at maximum of 6 liters oxygen flow per minute
    • Stable respiratory rate ≤30 breaths/min at maximum of 6 liters oxygen flow per minute
  5. Presence of at least 1 symptom characteristic for COVID-19 disease i.e., fever, cough or respiratory distress
  6. Willingness and ability to comply with the protocol
  7. Written informed consent given prior to any trial-related procedure

  8. For women of childbearing potential: Application of a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly) together with a barrier method between trial consent and 30 days after the last intake of the IMP.

    Highly effective forms of birth control are those with a failure rate less than 1% per year and include:

    • oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation
    • oral, injectable, or implantable progestogen-only hormonal contraceptives associated with inhibition of ovulation
    • intrauterine device or intrauterine hormone-releasing system
    • bilateral tubal occlusion
    • vasectomized partner (i.e., the patient's male partner underwent effective surgical sterilization before the female patient entered the clinical trial and is the sole sexual partner of the female patient during the clinical trial)
    • sexual abstinence (acceptable only if it is the patient's usual form of birth control/lifestyle choice; periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are no acceptable methods of contraception)

    Barrier methods of contraception include:

    • Condom
    • Occlusive cap (diaphragm or cervical/vault caps) with spermicidal gel/film/cream/suppository

  9. Male patients must agree not to father a child or to donate sperm starting at Screening, throughout the clinical trial and for 30 days after the last intake of the IMP. Male patients must also

    • abstain from sexual intercourse with a female partner (acceptable only if it is the patient's usual form of birth control/lifestyle choice), or
    • use adequate barrier contraception during treatment with the IMP and until at least 30 days after the last intake of the IMP, and
    • if they have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined in inclusion criterion 8
    • if they have a pregnant partner, they must use condoms while taking the IMP to avoid exposure of the fetus to the IMP

Exclusion criteria

Exclusion Criteria:

Underlying disease-related exclusion criteria

  1. Involvement in the trial is not in the patient's best interest according to the investigator's decision, including the presence of any condition that would, in the assessment of the investigator, not allow the protocol to be followed safely Note: The investigator should particularly consider exclusion of patients at increased risk for serious or fatal AEs in case of worsening of the pulmonary perfusion. This includes, but is not limited to, pre-existing pulmonary hypertension, severe chronic respiratory disease, severely increased risk for thromboembolic complications and moderate to severe left ventricular ejection fraction (LVEF) dysfunction. In addition, other known risk factors of highest risk of mortality in COVID-19 patients should be considered.
  2. Presence of respiratory failure, shock, and/or combined failure of other organs that requires ICU monitoring in the near foreseeable future
  3. Critical patients whose expected survival time \<48-72 hours

  4. Presence of the following laboratory values at screening:

    • White blood cell count (WBC) \<1.0 x 109/L
    • Platelet count \<100,000/mm³ (\<100 x 109/L)
    • Total bilirubin>2 x ULN
    • Alanine aminotransferase (ALT) or gamma glutamyl transferase (GGT) >5 x ULN
  5. Participation in any other interventional clinical trial
  6. Hospitalization primarily for other reasons than COVID-19 (including primarily for concomitant conditions during ongoing SARS-CoV-2 infection)
  7. Anticipated transport to a different hospital or institution, in particular when such transport is anticipated for pending ECMO or RRT treatment
  8. Clinical suspicion of a bacterial superinfection at Screening IMP-related exclusion criteria
  9. Patients who cannot take drugs orally
  10. Allergic or hypersensitive to the IMP or any of the ingredients

  11. Use of the following concomitant medications is prohibited from Screening to end of treatment with IMP in this trial (up to Day 14) if not indicated otherwise in this protocol:

    • Concurrent use of any mycophenolate mofetil or of methotrexate exceeding 17.5 mg weekly
    • Any medication known to significantly increase urinary elimination of uric acid, in particular lesinurad (Zurampic™) as well as uricosuric drugs such as probenecid
    • Current treatments for any malignancy, in particular irinotecan, paclitaxel, tretinoin, bosutinib, sorafenib, enasidenib, erlotinib, regorafenib, pazopanib and nilotinib
    • Any drug significantly restricting water diuresis, in particular vasopressin and vasopressin analogs
    • Use of rosuvastatin at daily doses higher than 10 mg
    • Arbidol and Colchicine
    • Any use of other DHODH inhibitors, including teriflunomide (Aubagio™) or leflunomide (Arava™)
    • Chloroquine and Hydroxychloroquine during the entire trial unless taken for indicated use before entering the trial
  12. Use of any investigational product within 8 weeks or 5x the respective half-life before the date of informed consent, whichever is longer, and throughout the duration of the trial General exclusion criteria
  13. Patients who have a "do not intubate" or "do not resuscitate" order (unless the patient waives in writing this order and will allow intubation for the duration of the trial period)
  14. Patients with end-stage liver disease (Child Pugh C score)
  15. History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (New York Heart Association [NYHA] class 3 or 4) Note: NYHA class 3: Cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. NYHA class 4: Cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
  16. Legal incapacity, limited legal capacity, or any other condition that makes the patient unable to provide consent for the trial
  17. Pregnant or breastfeeding
  18. An employee of an investigator or Sponsor or an immediate relative of an investigator or Sponsor
  19. Patients institutionalized due to judicial order
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
234 participants (actual)

Study arms

  • Experimental
    IMU-838

    twice-daily (BID) oral 22.5 mg IMU-838 (45 mg/day + SoC)

    Drug: IMU-838

  • Placebo comparator
    Placebo

    twice-daily (BID) oral placebo (+ SoC)

    Other: Placebo

Interventions

  • DrugIMU-838

    Tablets will be taken BID with a glass of water (if possible); one tablet each in the morning (15 to 50 min before a meal if applicable), and in the evening (2 hours after any meal if applicable). If the patient is intubated for ventilation, IMP is to be given via a gastric tube. The tablet has no coating and a homogeneous content and can be crushed into smaller pieces (if necessary) for dosing via gastric tube.

    Also known as: vidofludimus calcium

  • OtherPlacebo

    Matching placebo, twice-daily administration BID as described for the test product, identical number of tablets as given for IMU-838

06

What researchers measure

Primary outcomes

  1. Proportion of Patients Without Any Need for INV Until EoS

    Number of Participants Stratified as those With and Without the Need for INV Until End-of-study (EoS). For this outcome a worst case approach was used in which patients who were lost to follow-up or who discontinued the trial on or before Day 13 due to any other reason than death and discontinued with a last observed WHO clinical status no lower than that at Screening, and patients who died were considered as patients requiring INV.

    Time frame: Throughout the Study (Day 0 to Day 28)

Secondary outcomes

  1. Days in ICU Department

    Duration of ICU Treatment Until EoS for Only Patients Who Were Admitted to the ICU During the Trial.

    Time frame: Throughout the Study (Day 0 to Day 28 )

  2. All Cause Mortality (ITT Approach)

    28-day All-cause Mortality (including lost to follow-up): 'all-cause-mortality' includes all confirmed deaths and patients who discontinued the trial before Day 28 and for whom no outcome (alive or dead) could be determined at EoS; 'actual death' includes only those patients for which a fatal outcome was confirmed by Day 28.

    Time frame: Throughout the Study (Day 0 to Day 28 )

  3. Time to Clinical Improvement

    Defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the Modified WHO Ordinal Scale for Clinical Status (Modified WHO Ordinal Scale for Clinical Status), or live discharge from hospital without oxygen supplementation, whichever comes first. The 50% Kaplan-Meier quartile (median) of actual values per treatment arm is provided as outcome of this variable below.

    Time frame: Throughout the Study (Day 0 to Day 28)

  4. Days of Hospitalization

    Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)cacy:

    Time frame: Throughout the Study (Day 0 to Day 28 )

  5. Patients Free of Renal-replacement Therapy (RRT)* Until EoS

    Number of Patients Both for All Patients and Surviving Patients Free of Renal-replacement Therapy (RRT)\* Until EoS

    Time frame: Throughout the Study (Day 0 to Day 28 )

  6. Patients Required ECMO Until EoS

    Number and Percentage of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)\* until EoS.

    Time frame: Throughout the Study (Day 0 to Day 28 )

  7. Patients Free of INV Until Day 14*

    Number and persentage of patients free of INV until Day 14\*

    Time frame: Throughout the Study (Day 0 to Day 14 )

  8. Patients Free of RRT

    Percentage of patients free of RRT until Day 14\*

    Time frame: Day 0 to Day 14

  9. Number of Patients Free of ECMO

    Number of patients free of ECMO until Day 14.

    Time frame: Day 0 to Day 14

  10. Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1

    Numbers of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1( Modified WHO Ordinal Scale for Clinical Status)on Days 6, 14, and 28, where score 0 means no clinical or virological evidence of infection and score 8 is the worth outcome ( mens death).

    Time frame: on Days 6, 14, and 28

  11. Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)

    Percentage of Patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28.

    Time frame: on Days 6, 14, and 28

  12. Patients With Clinical Recovery

    Percentage of Patients With Clinical Recovery: Axillary Temp \<= 36.6 °C, or Oral Temp \<= 37.2 °C, or Rectal or Tympanic Temp \<= 37.8 °C and Respiratory Frequency \<= 24 Times/Min Without O2 Inhalation and O2 Saturation \>= 98% Without O2 Inhalation

    Time frame: Throughout the Study (Day 0 to Day 28 )

  13. Patients With Clinical Recovery

    Percentage of Patients With Clinical Recovery Oxygen Saturation ≥98% Without Oxygen Inhalation

    Time frame: Throughout the Study (Day 0 to Day 28 )

  14. Patients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation

    Percentage of patients with clinical improvement, defined as the time from first dose of IMP to an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first (Modified WHO Ordinal Scale for Clinical Status, where score 0 - for patient with no clinical or virological evidence of infections, score 9 - the worth scenario- death)

    Time frame: Throughout the Study (Day 0 to Day 28 )

  15. Percentage of Participants With WHO Status<=2

    Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

    Time frame: on Days 6, 14, and 28

  16. Duration of INV

    Duration of INV throughout the study. If no entry on the respective CRF page exists, the duration is set to 0 days for patients who performed Day 28 visit. Patients without Day 28 visit and without any entry on the respective CRF page are excluded from analysis.

    Time frame: Throughout the Study (Day 0 to Day 28 )

  17. Days on ECMO

    Duration of ECMO in days (duration set to 0 for those who did not require ECMO). No participants required ECMO.

    Time frame: Throughout the Study (Day 0 to Day 28)

  18. Days on RRT

    Duration of RRT in days (duration set to 0 for those who did not require RRT).No participants required RRT.

    Time frame: Throughout the Study (Day 0 to Day 28)

  19. Days of Auxiliary Oxygen Therapy

    Duration of auxiliary oxygen therapy (including all types of oxygen therapy)

    Time frame: Throughout the Study (Day 0 to Day 28)

  20. Days of Hospitalization

    Duration of hospitalization for survivors

    Time frame: Throughout the Study (Day 0 to Day 28)

  21. Participants With ICU Admission

    Percentage of Participants with ICU Admission at different time point

    Time frame: on Days 6, 14, and 28

  22. Probability of Death

    Probability of death derived from Kaplan Meier analyses

    Time frame: Throughout the Study (Day 0 to Day 28)

  23. Days to INV

    Time to first prescription of invasive ventilation (INV). The time to first prescription of INV, only patients with actual INV or prescription for INV are considered.

    Time frame: Throughout the Study (Day 0 to Day 28)

  24. Days to RRT

    Time to first prescription of RRT

    Time frame: Throughout the Study (Day 0 to Day 28)

  25. Days to ECMO

    Time to first prescription of ECMO

    Time frame: Throughout the Study (Day 0 to Day 28)

  26. Days to INV, RRT and ECMO

    Time to first prescription of INV, RRT, and ECMO. The time to first prescription of INV, only patients with actual INV or prescription for INV are considered.

    Time frame: Throughout the Study (Day 0 to Day 28)

  27. Probability of ICU Admission

    Overall probability of ICU admission derived from Kaplan Meier analyses.

    Time frame: Throughout the Study (Day 0 to Day 28)

  28. Cumulative Dose

    Cumulative Dose of Vasoactive Therapies and Days With Vasoactive Therapies (Daily Until Day 14)

    Time frame: Day 0 to day 14

  29. Time to Clinical Recovery

    Time of first assessments of parameters contributing to clinical recovery

    Time frame: Throughout the Study (Day 0 to EoS [Day 27 up to Day 42])

  30. Plasma Levels of IMU-838

    Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28

    Time frame: on Days 0, 1, 2, 3, 6, 14, and 28

  31. Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes

    Kaplan-Meier analyses were used to investigate a potential relationship between trough plasma levels of IMU-838 and time to clinical improvement and time to clinical recovery. Estimates of the clinical outcomes were evaluated separately for patients within each of the four quartiles of IMU-838 trough levels at Day 14.

    Time frame: Trough levels at Day 14; Clinical outcome: Day 0 to EoS (EoS = Day 27 up to Day 42)

  32. Number of Participants With Adverse Events (AEs) and Serious AEs

    Adverse events (AEs) and serious AEs. AEs-Hypertriglyceridemia,Increased glycosylated hemoglobin, Headache, Thrombocytosis, Hyperglycemia, AEs reported in ≥ 2.0% of patients in any treatment group included anemia, bradycardia, sinus bradycardia, tachycardia, pyrexia, hepatocellular injury, hematuria, hypertension and hypertensive crisis. SAEs- deep vein thrombosis,COVID-19 pneumonia, patient death.

    Time frame: Throughout the Study (Day 0 to Day 28)

  33. Vital Signs: Height

    Safety Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Time frame: at Baseline

  34. Vital Signs: Weight

    Safety Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Time frame: at Baseline

  35. Vital Signs: Body Temperature (ºC)

    Safety Body temperature can be measured axillary, oral, rectal or tympanic, but should be always measured by the same method for a patient. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Time frame: at Baseline

  36. Albumin Concentration at Various Time Points

    Clinical laboratory parameters: blood chemistry (Albumin concentration at various time points)

    Time frame: Throughout the Study (Day 0 to Day 28)

  37. Hematocrit Ratio at Various Time Points

    Clinical laboratory parameters: hematology- Hematocrit ratio at various time points

    Time frame: Throughout the Study (Day 0 to Day 28)

  38. Urine Creatinine at Various Time Points

    Clinical laboratory parameters: urinalysis- Urine creatinine at various time points

    Time frame: Throughout the Study (Day 0 to Day 28)

  39. Temperature

    Temperature data at different time point.

    Time frame: Throughout the Study (Day 0 to Day 28)

  40. D-dimer

    Disease markers

    Time frame: Throughout the Study (Day 0 to Day 28)

  41. Lactate Dehydrogenase (LDH)

    Blood levels of disease markers

    Time frame: Throughout the Study (Day 0 to Day 28)

  42. C-reactive Protein

    Blood levels of disease markers

    Time frame: Throughout the Study (Day 0 to Day 28)

  43. Troponin I

    Bood levels of disease markers

    Time frame: Throughout the Study (Day 0 to Day 28)

  44. Procalcitonin

    Blood levels of disease markers

    Time frame: Throughout the Study (Day 0 to Day 28)

  45. Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6

    Kaplan-Meier analyses were used to investigate a potential relationship between blood levels of D-Dimer and time to clinical improvement. Estimates of the clinical outcome were evaluated separately for patients within each of the four quartiles of D-Dimer levels at Day 6.

    Time frame: D-Dimer levels at Day 6; Clinical outcome: Day 0 to EoS (EoS = Day 27 up to Day 42)

  46. Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points

    Virologic markers: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples: changing of SARS-CoV-2 Viral Load in patients on Days 6,14,28

    Time frame: Throughout the Study (Day 0 to Day 28)

  47. Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples

    Virologic markers :Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Time course of SARS-CoV-2 viral load

    Time frame: Throughout the Study (Day 0 to Day 28)

  48. Number of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart

    Virologic markers: Qualitative Virologic Clearance in Spontaneous Sputum and Nasopharyngeal Swab Samples (= 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart)

    Time frame: Throughout the Study (Day 0 to Day 28)

  49. Rate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test

    Virologic markers: conversion to a negative SARS-CoV-2 (qualitative) test on Day 28.

    Time frame: on Day 28

  50. Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test

    Virologic markers : Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test Throughout the study. Only patients with viral load measured from nasopharyngeal swab and results provided by the central laboratory (Covance) were included.Conversion to a negative SARS-CoV-2 status is only assumed if a negative test is confirmed by all available subsequent assessments. This means for Day 28/early termination visit no confirmation is needed. If no conversion to a negative status is documented, patients will be censored for survival analysis at the time of the last documented positive test result.

    Time frame: Throughout the Study (Day 0 to Day 28)

  51. Interleukin (IL)-17

    The profiles of immune system biomarkers

    Time frame: Day 0, 6, 14 and Day 28

  52. Interleukin (IL)-1ß

    The profiles of immune system biomarkers

    Time frame: Day 0, 6, 14 and Day 28

  53. Interleukin (IL)-6

    The profiles of immune system biomarkers

    Time frame: Day 0, 6, 14 and 28

  54. Interferon Gamma (IFNγ)

    The profiles of immune system biomarkers

    Time frame: Day 0, 6, 14 and 28

  55. Tumor Necrosis Factor Alpha

    The profiles of immune system biomarkers

    Time frame: Day 0, 6, 14 and 28

  56. Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2

    Proportion of patients with IgA and/or IgG antibodies against SARS-CoV-2on at different time point

    Time frame: Day 6, 14 and 28

07

Results

Posted Nov 13, 2024

Participant flow

Participant flow — Overall Study
MilestoneIMU-838Placebo
Started110110
Completed9397
Not completed1713

Outcome measures

PrimaryProportion of Patients Without Any Need for INV Until EoS

Number of Participants Stratified as those With and Without the Need for INV Until End-of-study (EoS). For this outcome a worst case approach was used in which patients who were lost to follow-up or who discontinued the trial on or before Day 13 due to any other reason than death and discontinued with a last observed WHO clinical status no lower than that at Screening, and patients who died were considered as patients requiring INV.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Count of participants · Participants
Proportion of Patients Without Any Need for INV Until EoS
ParticipantsIMU-838Placebo
No INV needed98101
INV needed129
SecondaryDays in ICU Department

Duration of ICU Treatment Until EoS for Only Patients Who Were Admitted to the ICU During the Trial.

Time frame:
Throughout the Study (Day 0 to Day 28 )
Reported as:
Mean · days
Days in ICU Department
daysIMU-838Placebo
Days in ICU Department2.54 ± 7.242.33 ± 7.24
SecondaryAll Cause Mortality (ITT Approach)

28-day All-cause Mortality (including lost to follow-up): 'all-cause-mortality' includes all confirmed deaths and patients who discontinued the trial before Day 28 and for whom no outcome (alive or dead) could be determined at EoS; 'actual death' includes only those patients for which a fatal outcome was confirmed by Day 28.

Time frame:
Throughout the Study (Day 0 to Day 28 )
Reported as:
Count of participants · Participants
All Cause Mortality (ITT Approach)
ParticipantsIMU-838Placebo
actual death22
28 days all cause mortality (including lost to follow-up)98
SecondaryTime to Clinical Improvement

Defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the Modified WHO Ordinal Scale for Clinical Status (Modified WHO Ordinal Scale for Clinical Status), or live discharge from hospital without oxygen supplementation, whichever comes first. The 50% Kaplan-Meier quartile (median) of actual values per treatment arm is provided as outcome of this variable below.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Median · days
Time to Clinical Improvement
daysIMU-838Placebo
Time to Clinical Improvement13.70 (13.70 to 13.80)13.80 (13.70 to 13.80)
SecondaryDays of Hospitalization

Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)cacy:

Time frame:
Throughout the Study (Day 0 to Day 28 )
Reported as:
Mean · days
Days of Hospitalization
daysIMU-838Placebo
Days of Hospitalization13.49 ± 7.0014.35 ± 7.71
SecondaryPatients Free of Renal-replacement Therapy (RRT)* Until EoS

Number of Patients Both for All Patients and Surviving Patients Free of Renal-replacement Therapy (RRT)\* Until EoS

Time frame:
Throughout the Study (Day 0 to Day 28 )
Reported as:
Count of participants · Participants
Patients Free of Renal-replacement Therapy (RRT)* Until EoS
ParticipantsIMU-838Placebo
Patients Free of Renal-replacement Therapy (RRT)* Until EoS110110
SecondaryPatients Required ECMO Until EoS

Number and Percentage of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)\* until EoS.

Time frame:
Throughout the Study (Day 0 to Day 28 )
Reported as:
Count of participants · Participants
Patients Required ECMO Until EoS
ParticipantsIMU-838Placebo
Patients Required ECMO Until EoS00
SecondaryPatients Free of INV Until Day 14*

Number and persentage of patients free of INV until Day 14\*

Time frame:
Throughout the Study (Day 0 to Day 14 )
Reported as:
Count of participants · Participants
Patients Free of INV Until Day 14*
ParticipantsIMU-838Placebo
Patients Free of INV Until Day 14*10299
SecondaryPatients Free of RRT

Percentage of patients free of RRT until Day 14\*

Time frame:
Day 0 to Day 14
Reported as:
Count of participants · Participants
Patients Free of RRT
ParticipantsIMU-838Placebo
Patients Free of RRT110110
SecondaryNumber of Patients Free of ECMO

Number of patients free of ECMO until Day 14.

Time frame:
Day 0 to Day 14
Reported as:
Count of participants · Participants
Number of Patients Free of ECMO
ParticipantsIMU-838Placebo
Number of Patients Free of ECMO110110
SecondaryPatients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1

Numbers of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1( Modified WHO Ordinal Scale for Clinical Status)on Days 6, 14, and 28, where score 0 means no clinical or virological evidence of infection and score 8 is the worth outcome ( mens death).

Time frame:
on Days 6, 14, and 28
Reported as:
Number · participants
Patients With Improvement of at Least 2 Points (From Randomization) on the 9-category WHO Ordinal scale1
participantsIMU-838Placebo
Day 655
Day 144439
Day 289593
SecondaryPatients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)

Percentage of Patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28.

Time frame:
on Days 6, 14, and 28
Reported as:
Number · percentage of participants
Patients With Auxiliary Oxygen Therapy (Including All Types of Oxygen Therapy)
percentage of participantsIMU-838Placebo
Day 647.240.7
Day 1447.741.1
Day 2848.142.1
SecondaryPatients With Clinical Recovery

Percentage of Patients With Clinical Recovery: Axillary Temp \<= 36.6 °C, or Oral Temp \<= 37.2 °C, or Rectal or Tympanic Temp \<= 37.8 °C and Respiratory Frequency \<= 24 Times/Min Without O2 Inhalation and O2 Saturation \>= 98% Without O2 Inhalation

Time frame:
Throughout the Study (Day 0 to Day 28 )
Reported as:
Number · percent of patients
Patients With Clinical Recovery
percent of patientsIMU-838Placebo
Baseline3.73.6
Day 05.53.7
Day 717.412.0
Day 1021.719.5
Day 1440.245.8
Day 2869.365.6
SecondaryPatients With Clinical Recovery

Percentage of Patients With Clinical Recovery Oxygen Saturation ≥98% Without Oxygen Inhalation

Time frame:
Throughout the Study (Day 0 to Day 28 )
Reported as:
Number · percent of patients
Patients With Clinical Recovery
percent of patientsIMU-838Placebo
Day 717.412.0
Day 1440.245.8
Day 2869.365.6
SecondaryPatients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation

Percentage of patients with clinical improvement, defined as the time from first dose of IMP to an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first (Modified WHO Ordinal Scale for Clinical Status, where score 0 - for patient with no clinical or virological evidence of infections, score 9 - the worth scenario- death)

Time frame:
Throughout the Study (Day 0 to Day 28 )
Reported as:
Number · percent of patients
Patients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation
percent of patientsIMU-838Placebo
Patients With Clinical Improvement or Live Discharge From Hospital Without Oxygen Supplementation91.788.2
SecondaryPercentage of Participants With WHO Status<=2

Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

Time frame:
on Days 6, 14, and 28
Reported as:
Number · percentage of patients, WHO status <=2
Percentage of Participants With WHO Status<=2
percentage of patients, WHO status <=2IMU-838Placebo
Day 66.35.1
Day 1448.544.3
Day 2897.996.9
SecondaryDuration of INV

Duration of INV throughout the study. If no entry on the respective CRF page exists, the duration is set to 0 days for patients who performed Day 28 visit. Patients without Day 28 visit and without any entry on the respective CRF page are excluded from analysis.

Time frame:
Throughout the Study (Day 0 to Day 28 )
Reported as:
Mean · days
Duration of INV
daysIMU-838Placebo
Duration of INV0.00 (0 to 0.1)0.07 (0 to 7.0)
SecondaryDays on ECMO

Duration of ECMO in days (duration set to 0 for those who did not require ECMO). No participants required ECMO.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Number · days
Days on ECMO
daysIMU-838Placebo
Days on ECMO00
SecondaryDays on RRT

Duration of RRT in days (duration set to 0 for those who did not require RRT).No participants required RRT.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Number · days
Days on RRT
daysIMU-838Placebo
Days on RRT00
SecondaryDays of Auxiliary Oxygen Therapy

Duration of auxiliary oxygen therapy (including all types of oxygen therapy)

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Mean · days
Days of Auxiliary Oxygen Therapy
daysIMU-838Placebo
Days of Auxiliary Oxygen Therapy4.49 ± 7.013.86 ± 7.26
SecondaryDays of Hospitalization

Duration of hospitalization for survivors

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Mean · days
Days of Hospitalization
daysIMU-838Placebo
Days of Hospitalization13.53 (6.90 to 15.90)14.52 (7.30 to 19.00)
SecondaryParticipants With ICU Admission

Percentage of Participants with ICU Admission at different time point

Time frame:
on Days 6, 14, and 28
Reported as:
Number · percent of patients
Participants With ICU Admission
percent of patientsIMU-838Placebo
Day 63.73.8
Day 143.85.0
Day 284.05.0
SecondaryProbability of Death

Probability of death derived from Kaplan Meier analyses

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Number · Probability
Probability of Death
ProbabilityIMU-838Placebo
Probability of Death0.0190.019
SecondaryDays to INV

Time to first prescription of invasive ventilation (INV). The time to first prescription of INV, only patients with actual INV or prescription for INV are considered.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Median · days
Days to INV
daysIMU-838Placebo
Days to INV13.8 (13.8 to 13.8)6.0 (6.0 to 6.0)
SecondaryDays to RRT

Time to first prescription of RRT

Time frame:
Throughout the Study (Day 0 to Day 28)

No measurements were reported for this outcome.

SecondaryDays to ECMO

Time to first prescription of ECMO

Time frame:
Throughout the Study (Day 0 to Day 28)

No measurements were reported for this outcome.

SecondaryDays to INV, RRT and ECMO

Time to first prescription of INV, RRT, and ECMO. The time to first prescription of INV, only patients with actual INV or prescription for INV are considered.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Median · days
Days to INV, RRT and ECMO
daysIMU-838Placebo
Days to INV, RRT and ECMO13.8 (13.8 to 13.8)6.0 (6.0 to 6.0)
SecondaryProbability of ICU Admission

Overall probability of ICU admission derived from Kaplan Meier analyses.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Number · Probability
Probability of ICU Admission
ProbabilityIMU-838Placebo
Probability of ICU Admission0.0370.047
SecondaryCumulative Dose

Cumulative Dose of Vasoactive Therapies and Days With Vasoactive Therapies (Daily Until Day 14)

Time frame:
Day 0 to day 14
Reported as:
Mean · mg
Cumulative Dose
mgIMU-838
Cumulative Dose0
SecondaryTime to Clinical Recovery

Time of first assessments of parameters contributing to clinical recovery

Time frame:
Throughout the Study (Day 0 to EoS [Day 27 up to Day 42])
Reported as:
Median · days
Time to Clinical Recovery
daysIMU-838Placebo
Time to Clinical Recovery14.10 (12.90 to 27.80)14.10 (13.70 to 27.90)
SecondaryPlasma Levels of IMU-838

Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28

Time frame:
on Days 0, 1, 2, 3, 6, 14, and 28
Reported as:
Mean · ug/mL
Plasma Levels of IMU-838
ug/mLIMU-838
Baseline0.1108 ± 0.1135
Day 12.9234 ± 1.1493
Day 23.5724 ± 1.6299
Day 33.8572 ± 1.8606
Day 64.3607 ± 2.4872
Day 144.6514 ± 2.6506
Day 280.1014 ± 0.0093
SecondaryCorrelation of Trough Levels (Quartiles) to Selected Clinical Outcomes

Kaplan-Meier analyses were used to investigate a potential relationship between trough plasma levels of IMU-838 and time to clinical improvement and time to clinical recovery. Estimates of the clinical outcomes were evaluated separately for patients within each of the four quartiles of IMU-838 trough levels at Day 14.

Time frame:
Trough levels at Day 14; Clinical outcome: Day 0 to EoS (EoS = Day 27 up to Day 42)
Reported as:
Median · days
Correlation of Trough Levels (Quartiles) to Selected Clinical Outcomes
daysIMU-838
Time to clinical recovery - Q1 (Min to 3.1 µg/mL IMU-838)27.8 (13.2 to 29.1)
Time to clinical recovery - Q2 (3.1 to 4.2 µg/mL IMU-838)27.9 (12.9 to 28.8)
Time to clinical recovery - Q3 (4.2 to 6.0 µg/mL IMU-838)11.8 (6.0 to 13.7)
Time to clinical recovery - Q4 (6.0 µg/mL to Max IMU-838)11.3 (4.8 to 14.1)
Time to clinical improvement - Q1 (Min to 3.1 µg/mL IMU-838)13.7 (13.7 to 14.0)
Time to clinical improvement - Q2 (3.1 to 4.2 µg/mL IMU-838)13.8 (13.7 to 14.8)
Time to clinical improvement - Q3 (4.2 to 6.0 µg/mL IMU-838)13.7 (13.1 to 13.8)
Time to clinical improvement - Q4 (6.0 µg/mL to Max IMU-838)13.7 (11.0 to 13.9)
SecondaryNumber of Participants With Adverse Events (AEs) and Serious AEs

Adverse events (AEs) and serious AEs. AEs-Hypertriglyceridemia,Increased glycosylated hemoglobin, Headache, Thrombocytosis, Hyperglycemia, AEs reported in ≥ 2.0% of patients in any treatment group included anemia, bradycardia, sinus bradycardia, tachycardia, pyrexia, hepatocellular injury, hematuria, hypertension and hypertensive crisis. SAEs- deep vein thrombosis,COVID-19 pneumonia, patient death.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs) and Serious AEs
ParticipantsIMU-838Placebo
Any AE8169
Any serious AE24
SecondaryVital Signs: Height

Safety Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Time frame:
at Baseline
Reported as:
Mean · centimeters
Vital Signs: Height
centimetersIMU-838Placebo
Male178.1 ± 5.7175.6 ± 6.8
Female163.0 ± 5.5163.9 ± 4.4
SecondaryVital Signs: Weight

Safety Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Time frame:
at Baseline
Reported as:
Mean · kilograms
Vital Signs: Weight
kilogramsIMU-838Placebo
Male92.98 ± 18.8688.95 ± 14.05
Female77.88 ± 14.4674.09 ± 13.89
SecondaryVital Signs: Body Temperature (ºC)

Safety Body temperature can be measured axillary, oral, rectal or tympanic, but should be always measured by the same method for a patient. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Time frame:
at Baseline
Reported as:
Mean · degrees Celsius
Vital Signs: Body Temperature (ºC)
degrees CelsiusIMU-838Placebo
Vital Signs: Body Temperature (ºC)36.86 ± 0.5836.75 ± 0.53
SecondaryAlbumin Concentration at Various Time Points

Clinical laboratory parameters: blood chemistry (Albumin concentration at various time points)

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Mean · g/L
Albumin Concentration at Various Time Points
g/LIMU-838Placebo
Baseline39.4 ± 4.440.2 ± 4.7
Day 637.9 ± 4.238.7 ± 4.9
Day 1439.6 ± 4.640.3 ± 4.6
Day 2844.0 ± 3.744.0 ± 4.4
SecondaryHematocrit Ratio at Various Time Points

Clinical laboratory parameters: hematology- Hematocrit ratio at various time points

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Mean · ratio
Hematocrit Ratio at Various Time Points
ratioIMU-838Placebo
Baseline0.435 ± 0.0520.448 ± 0.053
Day 60.430 ± 0.0590.443 ± 0.053
Day 140.435 ± 0.0490.440 ± 0.051
Day 280.428 ± 0.0460.432 ± 0.052
SecondaryUrine Creatinine at Various Time Points

Clinical laboratory parameters: urinalysis- Urine creatinine at various time points

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Mean · umol/L
Urine Creatinine at Various Time Points
umol/LIMU-838Placebo
Baseline11368.1 ± 7672.011303.9 ± 6496.6
Day 69259.5 ± 5198.110214.0 ± 6551.3
Day 148940.8 ± 5771.010040.1 ± 6399.2
Day 2810498.2 ± 7776.111589.2 ± 6665.9
SecondaryTemperature

Temperature data at different time point.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Mean · degrees Celsius
Temperature
degrees CelsiusIMU-838Placebo
Baseline36.9 ± 0.5836.8 ± 0.53
Day 636.7 ± 0.3336.5 ± 0.42
Day 1436.4 ± 0.2436.4 ± 0.34
Day 2836.4 ± 0.2136.4 ± 0.34
SecondaryD-dimer

Disease markers

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Median · ng/mL
D-dimer
ng/mLIMU-838Placebo
Baseline529.5 (79 to 19520)473.0 (106 to 5647)
Day 14348.0 (91 to 19520)357.0 (60 to 19520)
Day 28343.0 (100 to 19520)332.5 (76 to 9076)
SecondaryLactate Dehydrogenase (LDH)

Blood levels of disease markers

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Median · nkat/L
Lactate Dehydrogenase (LDH)
nkat/LIMU-838Placebo
Baseline4176.0 (1900 to 14886)4059.0 (1900 to 14886)
Day 143167.0 (1650 to 11302)3117.0 (1850 to 10752)
Day 283375.5 (1650 to 7918)3267.0 (1650 to 15053)
SecondaryC-reactive Protein

Blood levels of disease markers

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Median · nmol/L
C-reactive Protein
nmol/LIMU-838Placebo
Baseline320.4826 (5.7144 to 2682.911)245.2430 (5.7144 to 2362.904)
Day 1427.61960 (5.7144 to 6328.698)20.95280 (5.7144 to 858.1124)
Day 2823.81000 (5.7144 to 207.6232)16.19080 (5.7144 to 1447.648)
SecondaryTroponin I

Bood levels of disease markers

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Median · ug/L
Troponin I
ug/LIMU-838Placebo
Baseline0.00860 (0.0086 to 0.0904)0.00860 (0.0086 to 0.1054)
Day 140.00860 (0.0086 to 0.0812)0.00860 (0.0086 to 1.0152)
Day 280.00860 (0.0086 to 0.0542)0.00860 (0.0086 to 0.1053)
SecondaryProcalcitonin

Blood levels of disease markers

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Median · ng/mL
Procalcitonin
ng/mLIMU-838Placebo
Baseline0.0695 (0.020 to 0.513)0.0530 (0.020 to 0.568)
Day 140.0410 (0.020 to 2.880)0.0340 (0.020 to 0.120)
Day 280.0380 (0.020 to 0.246)0.0350 (0.020 to 1.840)
SecondaryCorrelation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6

Kaplan-Meier analyses were used to investigate a potential relationship between blood levels of D-Dimer and time to clinical improvement. Estimates of the clinical outcome were evaluated separately for patients within each of the four quartiles of D-Dimer levels at Day 6.

Time frame:
D-Dimer levels at Day 6; Clinical outcome: Day 0 to EoS (EoS = Day 27 up to Day 42)
Reported as:
Median · days
Correlation of Time to Clinical Improvement With Quartiles of D-Dimer Blood Levels at Day 6
daysIMU-838Placebo
Q 1 (Min to 275 ng/mL D-Dimer)13.8 (7.6 to 14.8)13.8 (13.7 to 13.8)
Q 2 (275 to 450 ng/mL D-Dimer)13.7 (12.0 to 13.9)13.8 (10.8 to 15.8)
Q 3 (450 to 731 ng/mL D-Dimer)13.8 (13.7 to 14.8)13.8 (13.0 to 14.8)
Q 4 (731 ng/mL to Max D-Dimer)13.7 (12.0 to 14.0)13.8 (13.7 to 14.0)
SecondaryChanging in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points

Virologic markers: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples: changing of SARS-CoV-2 Viral Load in patients on Days 6,14,28

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Mean · Change in log10 copies
Changing in Log 10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples at Various Time Points
Change in log10 copiesIMU-838Placebo
Day 2-10020591.1 ± 38272166.5-62534293.5 ± 380490492.5
Day 6-12849771.3 ± 49984377.5-84355538.5 ± 416667915.1
Day 14-13617000.9 ± 51579374.1-89534493.9 ± 429884542.5
Day 28-15195922.3 ± 54087022.5-44774028.6 ± 249373454.1
SecondaryMean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples

Virologic markers :Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Time course of SARS-CoV-2 viral load

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Mean · log10 Copies
Mean Viral Load - log10 Copies in Spontaneous Sputum and Nasopharyngeal Swab Samples
log10 CopiesIMU-838Placebo
Baseline10966569.9 ± 46215130.575572844.7 ± 389541813.1
Day 633277.7 ± 168585.9581813.6 ± 3313425.6
Day 1437642.6 ± 281630.2483522.2 ± 3851254.5
Day 28181.6 ± 673.9369.7 ± 2133.1
SecondaryNumber of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart

Virologic markers: Qualitative Virologic Clearance in Spontaneous Sputum and Nasopharyngeal Swab Samples (= 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart)

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Count of participants · Participants
Number of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart
ParticipantsIMU-838Placebo
Number of Participants With 2 Consecutive Negative SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction Tests at Least 24 Hours Apart6977
SecondaryRate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test

Virologic markers: conversion to a negative SARS-CoV-2 (qualitative) test on Day 28.

Time frame:
on Day 28
Reported as:
Count of participants · Participants
Rate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test
ParticipantsIMU-838Placebo
Rate of Conversion to a Negative SARS-CoV-2 (Qualitative) Test5760
SecondaryTime to Conversion to a Negative SARS-CoV-2 (Qualitative) Test

Virologic markers : Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test Throughout the study. Only patients with viral load measured from nasopharyngeal swab and results provided by the central laboratory (Covance) were included.Conversion to a negative SARS-CoV-2 status is only assumed if a negative test is confirmed by all available subsequent assessments. This means for Day 28/early termination visit no confirmation is needed. If no conversion to a negative status is documented, patients will be censored for survival analysis at the time of the last documented positive test result.

Time frame:
Throughout the Study (Day 0 to Day 28)
Reported as:
Mean · days
Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test
daysIMU-838Placebo
Time to Conversion to a Negative SARS-CoV-2 (Qualitative) Test13.8 (12.8 to 14.1)14.0 (13.7 to 27.8)
SecondaryInterleukin (IL)-17

The profiles of immune system biomarkers

Time frame:
Day 0, 6, 14 and Day 28
Reported as:
Mean · pg/mL
Interleukin (IL)-17
pg/mLIMU-838Placebo
Baseline5.860 ± 0.0005.860 ± 0.000
Day 65.860 ± 0.0005.885 ± 0.177
Day 145.924 ± 0.6215.860 ± 0.000
Day 285.866 ± 0.0585.892 ± 0.308
SecondaryInterleukin (IL)-1ß

The profiles of immune system biomarkers

Time frame:
Day 0, 6, 14 and Day 28
Reported as:
Mean · ng/L
Interleukin (IL)-1ß
ng/LIMU-838Placebo
Baseline0.668 ± 0.1590.654 ± 0.032
Day 61.014 ± 1.8651.100 ± 2.165
Day 140.976 ± 1.9550.862 ± 0.970
Day 280.984 ± 2.2400.662 ± 0.076
SecondaryInterleukin (IL)-6

The profiles of immune system biomarkers

Time frame:
Day 0, 6, 14 and 28
Reported as:
Mean · ng/L
Interleukin (IL)-6
ng/LIMU-838Placebo
Baseline6.217 ± 8.0375.093 ± 6.438
Day 65.441 ± 14.2718.435 ± 30.854
Day 147.697 ± 25.5145.536 ± 26.081
Day 283.437 ± 14.3171.468 ± 1.879
SecondaryInterferon Gamma (IFNγ)

The profiles of immune system biomarkers

Time frame:
Day 0, 6, 14 and 28
Reported as:
Mean · pg/mL
Interferon Gamma (IFNγ)
pg/mLIMU-838Placebo
Baseline94.364 ± 166.46592.190 ± 153.798
Day 628.654 ± 90.12724.141 ± 77.850
Day 1410.469 ± 13.22438.192 ± 150.623
Day 2817.013 ± 33.76214.452 ± 21.067
SecondaryTumor Necrosis Factor Alpha

The profiles of immune system biomarkers

Time frame:
Day 0, 6, 14 and 28
Reported as:
Mean · ng/L
Tumor Necrosis Factor Alpha
ng/LIMU-838Placebo
Baseline3.084 ± 3.3143.310 ± 5.071
Day 66.617 ± 21.4618.020 ± 18.418
Day 147.974 ± 18.52612.064 ± 12.064
Day 284.778 ± 9.2933.717 ± 5.690
SecondaryImmunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2

Proportion of patients with IgA and/or IgG antibodies against SARS-CoV-2on at different time point

Time frame:
Day 6, 14 and 28
Reported as:
Number · percent of patients
Immunoglobulin (Ig)A and/or IgG Antibodies Against SARS-CoV-2
percent of patientsIMU-838Placebo
Day 686.083.8
Day 1496.994.3
Day 2898.396.9

Adverse events

Collected over Adverse event data were collected until Day 60 after randomization. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
IMU-8382/110 (1.8%)2/110 (1.8%)79/110 (71.8%)
Placebo2/110 (1.8%)4/110 (3.6%)65/110 (59.1%)
Most frequent serious events
Most frequent serious events
EventIMU-838Placebo
DeathInvestigations2/1102/110
PneumoniaRespiratory, thoracic and mediastinal disorders0/1101/110
ThrombosisVascular disorders0/1101/110
Respiratory distressRespiratory, thoracic and mediastinal disorders0/1101/110
Most frequent other events
Showing 10 of 13
Most frequent other events
EventIMU-838Placebo
HypertriglyceridaemiaMetabolism and nutrition disorders23/11013/110
Glycosylated haemoglobin increasedInvestigations10/1106/110
HyperglycaemiaMetabolism and nutrition disorders5/1108/110
HeadacheNervous system disorders8/1105/110
BradycardiaCardiac disorders4/1107/110
TachycardiaCardiac disorders7/1102/110
Hepatocellular injuryHepatobiliary disorders3/1107/110
HaematuriaRenal and urinary disorders7/1104/110
AnaemiaBlood and lymphatic system disorders4/1106/110
Sinus bradycardiaCardiac disorders6/1105/110

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)IMU-838PlaceboTotal
<=18 years000
Between 18 and 65 years8383166
>=65 years272754
Age, Continuous
Age, Continuous(years)IMU-838PlaceboTotal
Mean54.5 ± 13.453.7 ± 14.254.1 ± 13.8
Sex: Female, Male
Sex: Female, Male(Participants)IMU-838PlaceboTotal
Female5546101
Male5564119
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)IMU-838PlaceboTotal
Race — White110107217
Race — Asian011
Race — Black or African American011
Race — Other011
08

Study locations

4 sites
  • Military Medical Academy, Clinic of Infectious Diseases
    Sofia, 1606, Bulgaria
  • UMHATEM N.I.Pirogov, Clinic of internal diseases
    Sofia, 1606, Bulgaria
  • University Hospital Frankfurt, Infectious Diseases
    Frankfurt, 60590, Germany
  • Clinic of the Hannover Medical School, Pneumology Clinic
    Hannover, 30625, Germany
09

References and documents

Publications

  • Vehreschild MJGT, Atanasov P, Yurko K, Oancea C, Popov G, Smesnoi V, Placinta G, Kohlhof H, Vitt D, Peelen E, Mihajlovic J, Muehler AR. Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial. Infect Dis Ther. 2022 Dec;11(6):2159-2176. doi: 10.1007/s40121-022-00690-0. Epub 2022 Oct 15. PubMed 36242741 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 4, 2020

Documents are hosted by the registry — open the source record to download them.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 13, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT04379271
Lead sponsor
Immunic AG
Collaborators
FGK Clinical Research GmbH
Responsible party
Sponsor
First posted
May 7, 2020
Start date
Jun 11, 2020
Primary completion
Jan 12, 2021
Completion
Feb 23, 2021
Results posted
Nov 13, 2024
Last update
Nov 13, 2024

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2024. You cannot join it, but the record below documents what was studied.

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Discussion

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