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ODYSSEY: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Tradipitant in Treating Inflammatory Lung Injury and Improving Clinical Outcomes Associated With Severe or Critical COVID-19 Infection

Trial Profile

ODYSSEY: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Tradipitant in Treating Inflammatory Lung Injury and Improving Clinical Outcomes Associated With Severe or Critical COVID-19 Infection

Status: Discontinued
Phase of Trial: Phase III

Latest Information Update: 09 Feb 2023

At a glance

  • Drugs Tradipitant (Primary) ; Tradipitant (Primary)
  • Indications COVID 2019 infections; COVID-19 pneumonia
  • Focus Registrational; Therapeutic Use
  • Acronyms COVIDL1; ODYSSEY
  • Sponsors Vanda Pharmaceuticals
  • Most Recent Events

    • 01 Sep 2021 Results reporting carriers of stop-gain IFNAR2 (NM_000874:exon9:c.C966A:p.Y322X) in cohort of severe COVID-19 patients published in the Journal of Global Antimicrobial Resistance
    • 03 Aug 2021 Primary endpoint has not been met. (Time to improvement on a 7-point ordinal scale as compared to baseline), according to a Vanda Pharmaceuticals media release.
    • 03 Aug 2021 According to a Vanda Pharmaceuticals media release, company will continue the genetics component of the study with the goal of identifying genetic susceptibility factors contributing to the incidence of severe pneumonia among patients infected with the SARS-CoV-2 virus.

Trial Overview

Outcome

Primary endpoint not met - negative

Purpose

This is a randomized, double-blind placebo-controlled trial to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-19 infection. On evaluation for enrollment, participant will need to meet all inclusion and exclusion criteria. If participant consents, they will be randomized 1:1 to treatment with either tradipitant 85 mg PO BID or placebo in addition to standard of care for COVID-19 infection as per the protocol at the treating hospital. NEWS 2 will be assessed at screening and daily following randomization. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.

Comments

According to a Vanda Pharmaceuticals media release, an independent data and safety monitoring board (DSMB) recommended to terminate this study for futility, based on the planned interim analysis that determined that the study is unlikely to show a significant difference between treatment arms at the pre-specified primary endpoint. The DSMB also determined that there were no safety concerns that contributed to its recommendation.

Primary Endpoints

Not met, 03 Aug 2021

Time to improvement on a 7-point ordinal scale as compared to baseline

time_frame: 14 days or discharge [1]

The primary endpoint is the percentage of responders at day 28, as defined by an improvement of 2 or more points on a clinical status 7-point scale as compared to baseline. The primary endpoint will be summarized in Kaplan-Meier survival curve, and the treatment difference will be tested by the log-rank test in the ITT population.

The statistical analyses will be detailed in the statistical analysis plan (SAP).
Timepoint: Day 28

Other Endpoints

Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6)

time_frame: 14 days or discharge

Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples

time_frame: 14 days or discharge

In-hospital mortality

time_frame: 14 days or discharge

Mean change in NEWS2 score from baseline

time_frame: 14 days or discharge

Understand the effect of genetics for treatment response through whole genome sequence of the participant and the COVID-19 virus

time_frame: 14 days or discharge

Reduction from baseline of NRS for cough

time_frame: 14 days or discharge

Reduction from baseline of NRS for nausea

time_frame: 14 days or discharge

Time to normalization of fever for at least 48 hours

time_frame: 14 days or discharge

Time to improvement in oxygenation for at least 48 hours

time_frame: 14 days or discharge [2]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
COVID-19 pneumonia treatment severe

Biomarker

NCT Number Biomarker Name Biomarker Function
NCT04326426 Interleukin-6 (IL-6) Outcome Measure
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Subjects

  • Subject Type patients
  • Number

    Planned: 300

    Actual: 153

  • Sex male & female
  • Age Group 18-90 years; adult; elderly

Patient Inclusion Criteria

- Adults aged 18-90 - Confirmed laboratory COVID-19 infection by RT-PCR - Meeting severe or critical criteria of COVID-19 infection as defined at treating hospital - Confirmed pneumonia by chest radiograph or computed tomography - Fever defined as temperature ≥ 36.6 °C armpit, ≥ 37.2 °C oral, or ≥ 37.8 °C rectal - Oxygen saturation less than 92%

Patient Exclusion Criteria

- Recent use of illicit drugs or alcohol abuse - Known allergy to tradipitant or other neurokinin-1 antagonists - Pregnancy - Known HIV, HBV, or HCV infection - Malignant tumor, other serious systemic diseases - Inability to provide informed consent or to have an authorized relative or designated person provide informed consent, or to comply with the protocol requirements

Trial Details

Identifiers

Identifier Owner
NCT04326426 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-005526-29 European Clinical Trials Database
VLY686-3501 -
VP-VLY686-3501 -

Organisations

  • Sponsors Vanda Pharmaceuticals
  • Affiliations Vanda Pharmaceuticals

Trial Dates

  • Initiation Dates

    Planned : 01 Apr 2020

    Actual : 13 Apr 2020

  • Primary Completion Dates

    Planned : 01 Aug 2020

  • End Dates

    Planned : 31 Aug 2020

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location France; USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
TradipitantPrimary Drug Nasogastric
-
TradipitantPrimary Drug Oral Capsule

Tradipitant

Tradipitant 85 mg PO BID
Drug: Tradipitant (Neurokinin-1 antagonist)

Placebo

2 capsules of matching placebo
Drug: Placebo (Matching placebo)

Results

Therapeutic efficacy

In interim data from the phase III ODYSSEY trial, 14 day treatment with tradipitant demonstrated statistically significant treatment accelerated clinical improvement by day 7 (HR = 2.55, p = 0.0375) in 60 patients with inflammatory lung injury associated with severe or critical COVID-2019 infections. The benefit was generally consistent among patients of varying degree of severity at baseline. Tradipitant showed numerically improved median time to clinical improvement by day 28 (HR = 1.55, p = 0.2254) when compared with placebo, with median time to improvement 10 days for tradipitant and 28 days for placebo. Overall rates of improvement were similar for both treatment arm and placebo arm and was observed in 57% of patients treated with tradipitant and 50% for placebo.The mortality rate was also similar between the treatment groups with 14.2% for tradipitant and 16.6% for placebo [3]

Publications

  1. Vanda Pharmaceuticals. Vanda Pharmaceuticals' Interim Analysis from ODYSSEY Study Shows Tradipitant may Accelerate Clinical Improvement in Patients with COVID-19 Pneumonia. Media-Rel 2020;.

    Media Release
  2. Loss-of-function mutations in IFNAR2 in COVID-19 severe infection susceptibility. Internet-Doc 2021;.

    Available from: URL: https://www.sciencedirect.com/science/article/pii/S2213716521001569?via%3Dihub
  3. Smieszek S. Late Breaking Abstract - Increased Substance P levels in COVID-19 hospitalized patients. ERS-2021 2021; abstr. N/A.

    Available from: URL: https://erj.ersjournals.com/content/58/suppl_65/OA4114

Authors

Author Total Publications First Author Last Author
Smieszek S 1 1 1
Vanda Pharmaceuticals 1 1 1

Trial Centres

Centres

Centre Name Location Trial Centre Country
Lenox Hill Hospital Northwell Health New York, New York USA
Vanda Pharmaceuticals
-
-

Trial History

Event Date Event Type Comment
09 Feb 2023 Other trial event Last checked against European Clinical Trials Database record. Updated 09 Feb 2023
10 Apr 2022 Other trial event According to ClinicalTrials.gov, the recruitment status of this study is unknown because the information has not been verified recently (last verified April 2020). Updated 10 Apr 2022
10 Apr 2022 Other trial event Last checked against the ClinicalTrials.gov record. Updated 10 Apr 2022
06 Oct 2021 Other trial event New source identified and integrated: (European Clinical trials database: EudraCT2020-005526-29). Updated 06 Oct 2021
08 Sep 2021 Results Results exploring the genetic variants associated with attenuated Substance P responses from patients enrolled in ongoing ODYSSEY COVID-19 clinical study (NCT04326426) presented at the 31st Annual Congress of the European Respiratory Society Updated 09 Feb 2022
01 Sep 2021 Results Results reporting carriers of stop-gain IFNAR2 (NM_000874:exon9:c.C966A:p.Y322X) in cohort of severe COVID-19 patients published in the Journal of Global Antimicrobial Resistance Updated 09 Aug 2021
03 Aug 2021 Endpoint not met Primary endpoint has not been met. (Time to improvement on a 7-point ordinal scale as compared to baseline), according to a Vanda Pharmaceuticals media release. Updated 06 Aug 2021
03 Aug 2021 Other trial event According to a Vanda Pharmaceuticals media release, company will continue the genetics component of the study with the goal of identifying genetic susceptibility factors contributing to the incidence of severe pneumonia among patients infected with the SARS-CoV-2 virus. Updated 05 Aug 2021
03 Aug 2021 Other trial event According to a Vanda Pharmaceuticals media release, an independent data and safety monitoring board (DSMB) recommended to terminate this study for futility, based on the planned interim analysis that determined that the study is unlikely to show a significant difference between treatment arms at the pre-specified primary endpoint. The DSMB also determined that there were no safety concerns that contributed to its recommendation. Updated 05 Aug 2021
03 Aug 2021 Status change - discontinued Status changed from recruiting to discontinued, according to a Vanda Pharmaceuticals media release. Updated 05 Aug 2021
18 Aug 2020 Other trial event According to a Vanda Pharmaceuticals media release, as of July 15, 2020, 60 patients had enrolled and completed the study.The results from this interim analysis will be submitted for publication in a peer reviewed journal. Updated 22 Aug 2020
18 Aug 2020 Interim results Interim Results (n=60) published in the Vanda Pharmaceuticals Media Release Updated 22 Aug 2020
05 Aug 2020 Other trial event According to a Vanda Pharmaceuticals media release, interim analysis will be conducted to determine next steps. Updated 10 Aug 2020
06 May 2020 Other trial event According to a Vanda Pharmaceuticals media release, results from this study are expected in the third quarter of 2020. Updated 11 May 2020
20 Apr 2020 Biomarker Update Biomarkers information updated Updated 17 Sep 2021
15 Apr 2020 Other trial event According to a Vanda Pharmaceuticals media release, first patient is enrolled in Vanda's clinical trial, ODYSSEY VLY-686-3501 (NCT04326426), yesterday at Lenox Hill Hospital in New York City. Updated 22 Apr 2020
15 Apr 2020 Other trial event According to a Vanda Pharmaceuticals media release, Dr. Mina, Section Chief of Pulmonary Medicine, Director of Pulmonary & Critical Care Fellowship at Lenox Hill Hospital, is a lead ODYSSEY study investigator Updated 22 Apr 2020
15 Apr 2020 Other trial event According to a Vanda Pharmaceuticals media release, With the strong leadership and health expertise of Northwell Health, we expect to be able to accelerate enrollment in this study and provide results in the coming months Updated 22 Apr 2020
14 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting, according to a Vanda Pharmaceuticals media release. Updated 22 Apr 2020
02 Apr 2020 Other trial event According to a Vanda Pharmaceuticals media release, the company has received FDA permission to proceed with the study and announced the initiation of this study. Updated 13 Apr 2020
02 Apr 2020 Other trial event According to a Vanda Pharmaceuticals media release, the study will begin at New York area hospitals and will enroll hospitalized patients with COVID-19 ARDS. Updated 13 Apr 2020
02 Apr 2020 Other trial event According to a Vanda Pharmaceuticals media release, the company start enrolling patients this month. Updated 13 Apr 2020
01 Apr 2020 New trial record New trial record Updated 01 Apr 2020

References

  1. Vanda Pharmaceuticals. Vanda Pharmaceuticals Closes Enrollment In The ODYSSEY Study Comparing Tradipitant And Placebo In Hospitalized COVID-19 Pneumonia Patients. Media-Rel 2021;.

    Media Release
  2. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.

    Available from: URL: http://clinicaltrials.gov
  3. Vanda Pharmaceuticals. Vanda Pharmaceuticals' Interim Analysis from ODYSSEY Study Shows Tradipitant may Accelerate Clinical Improvement in Patients with COVID-19 Pneumonia. Media-Rel 2020;.

    Media Release
  4. Loss-of-function mutations in IFNAR2 in COVID-19 severe infection susceptibility. Internet-Doc 2021;.

    Available from: URL: https://www.sciencedirect.com/science/article/pii/S2213716521001569?via%3Dihub
  5. Vanda Pharmaceuticals. Vanda Pharmaceuticals Reports First Quarter 2020 Financial Results. Media-Rel 2020;.

    Media Release
  6. Vanda Pharmaceuticals. Vanda Pharmaceuticals Announces the Initiation of ODYSSEY, an FDA Approved Clinical Study of Tradipitant in Hospitalized Patients with Severe COVID-19 Pneumonia. Media-Rel 2020;.

    Media Release
  7. European Clinical Trials Database. Trial-Reg 2023;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  8. Vanda Pharmaceuticals. Vanda Pharmaceuticals Reports Second Quarter 2020 Financial Results. Media-Rel 2020;.

    Media Release
  9. Smieszek S. Late Breaking Abstract - Increased Substance P levels in COVID-19 hospitalized patients. ERS-2021 2021; abstr. N/A.

    Available from: URL: https://erj.ersjournals.com/content/58/suppl_65/OA4114
  10. Vanda Pharmaceuticals. Vanda Pharmaceuticals, Northwell Health Conduct ODYSSEY Trial In Patients With Severe COVID-19 Pneumonia. Media-Rel 2020;.

    Media Release
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