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Off-the-shelf NK Cells (KDS-1000) as Immunotherapy for COVID-19

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04797975
Recruitment Status : Withdrawn (The sponsor decided to withdraw this study)
First Posted : March 15, 2021
Last Update Posted : August 30, 2021
Sponsor:
Information provided by (Responsible Party):
Kiadis Pharma

Brief Summary:
It is hypothesized that immunotherapy with off-the-shelf NK cells (KDS-1000) early in the course of COVID-19 disease is safe and may augment innate immunity, thereby limiting disease progression and improving survival.

Condition or disease Intervention/treatment Phase
Covid19 Biological: KDS-1000 Other: Placebo Phase 1 Phase 2

Detailed Description:
Several publications have suggested a potential role of NK cells, an essential part of the early innate response system, in the management of viral infections like COVID-19. Clinical data has shown that COVID-19 disease severity is correlated with a reduction in the number of NK cells, exhaustion of NK cells and the lack of certain mature, potent NK cell phenotypes. The power of NK cells to fight various other viral infections, such as caused by CMV, HBV and hepatitis C virus (HCV), influenza virus and human immunodeficiency virus (HIV) have been well described, with a durable change in the NK cell profile towards those more mature and potent phenotypes in recovered patients. In view of the lack of (functional) NK cells in patients with COVID-19, adoptive NK cell therapy with KDS-1000 cells may improve survival and reduce rates of disease progression from SARS-CoV-2 infection. Adoptive transfer of expanded NK cells (KDS-1000) early in the course of disease may augment innate immunity, thereby limiting disease progression and could confer a survival benefit to patients infected with SARS-CoV-2.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Multicenter Randomized Double-blind Placebo-controlled Trial of Off-the-shelf Natural Killer Cells (KDS-1000) as Immunotherapy for Adult Patients With Mild to Moderate COVID-19 Symptoms at Risk for Complications
Estimated Study Start Date : December 2020
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: KDS-1000
NK cells expanded ex vivo using PM21 membrane particles:
Biological: KDS-1000

Non-randomized part of study:

  • At the beginning of each dose level (Cohort), 3 patients will receive KDS-1000. These initial patients will be enrolled in a staggered manner to ensure detection of any early safety signals.

Randomized part of the study (Can start when there are no safety concerns in the non-randomized cohorts):

  • Cohort 1: Low Dose, 2x10E8 cells/dose
  • Cohort 2: High Dose, 1x10E9 cells/dose

Placebo Comparator: Control
0.9% Normal Saline
Other: Placebo
0.9% Normal Saline




Primary Outcome Measures :
  1. Determine the safety of KDS-1000 given at low and high doses compared to placebo by collecting the rate and severity of adverse events (AE) [ Time Frame: 28 Days ]
    Rate and severity of AE.


Secondary Outcome Measures :
  1. Determine the efficacy KDS-1000 given at low and high doses compared to placebo by COVID-19 specific questionnaire. [ Time Frame: 90 Days ]
    Improvement in COVID-19 disease symptoms/progression of disease.

  2. Determine the efficacy KDS-1000 given at low and high doses compared to placebo by measurement of SARS-CoV-2 clearance. [ Time Frame: 28 days ]
    Determined by real time reverse transcription polymerase chain reaction (rRT-PCR).

  3. Determine the safety of KDS-1000 given at low and high doses compared to placebo by collecting the rate and severity of AE. [ Time Frame: 90 Days ]
    Rate and severity of AE.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients are 18-70 years of age;
  2. Patients must have at least one of the following risk factors for developing severe COVID-19 disease:

    1. Age 50 to 70 years;
    2. Obesity (body mass index (BMI) of 30 or greater);
    3. Hypertension;
    4. Current smoker;
    5. Diabetes mellitus (Type 1 or type 2);
    6. Stable cardiac disease.
  3. Experiencing symptoms of mild to moderate COVID-19 not requiring supplemental oxygen;
  4. Having confirmed infection with SARS-CoV-2, defined as detection of SARS-CoV-2 from nasopharyngeal swab or lower respiratory tract specimen;
  5. Karnofsky Performance Score ≥70%;
  6. Enrolled within the first 4 days of onset of symptoms;
  7. Able and willing to comply with the protocol for duration of the study, including 24 hour hospitalization for study drug administration and monitoring, and compliance with follow-up visit schedule;
  8. Signed IRB approved informed consent.

Exclusion Criteria:

  1. Patient is at high-risk for severe COVID-19 due to co-morbidities defined as:

    1. Underlying lung disease such as emphysema, chronic lung disease, COPD, asthma, chronic bronchiectasis or respiratory failure requiring baseline oxygen (O2) support;
    2. Immunocompromised host status due to cancer, transplant, or other causes of immunodeficiency;
    3. Immunosuppressive therapy, including but not limited to the following:

      • Corticosteroids (except topical corticosteroids);
      • Interleukin (IL)-6 or Tumor necrosis factor alpha (TNFα) blockade;
      • Other immunotherapies.
  2. Patient with the following signs of abnormal organ or bone marrow function as defined below:

    • AST(SGOT) and/or ALT(SGPT) > 3 x upper limit of normal (ULN);
    • Serum (total) bilirubin > 1.5 x ULN;
    • Creatinine Clearance ≤ 30 mL/min (by Modification of Diet in Renal Disease (MDRD) formula);
    • Hemoglobin < 9 g/dL;
    • Thrombocytes ≤ 75.000/uL;
    • Absolute neutrophil count (ANC) ≤ 1.500/uL;
    • Prothrombin time (PT) or activated partial thromboplastin (aPTT) time >1.5 × ULN;
  3. Patient has been admitted to the (ICU);
  4. Patients with QT prolongation, history of "torsades de pointes" or ventricular arrhythmia (if they are scheduled to receive diphenhydramine);
  5. Patient with a known history of allergic reactions to any constituent of the product, including a known history of allergic reactions to cellular products or DMSO;
  6. Pregnant (positive pregnancy test) or breast-feeding female patients;
  7. Women of childbearing potential who are sexually active and men who have sexual contact with a female of childbearing potential: not willing to use reliable methods of contraception (oral contraceptives, intrauterine device, hormone implants, contraceptive injection or abstinence) up to 90 days post injection of study medication;
  8. Participation in other COVID-19 studies involving experimental treatments or vaccines for COVID-19. Participation in other observational studies could be allowed if they do not interfere with protocol compliance or blood draws;
  9. Patients with a history or current evidence of alcohol or drug abuse or dependence, or recreational use of illicit drugs including use of medical marijuana;
  10. Vulnerable populations such as those currently incarcerated or homeless;
  11. Any other condition which in the opinion of the investigator makes the patient ineligible for participation in the study.
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Responsible Party: Kiadis Pharma
ClinicalTrials.gov Identifier: NCT04797975    
Other Study ID Numbers: KNK-COV-001
First Posted: March 15, 2021    Key Record Dates
Last Update Posted: August 30, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kiadis Pharma:
Cell Therapy
COVID-19
Natural Killer Cells
NK Cells
Off-the-shelf
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases