Clinical trial NCT04338958: Ruxolitinib in Covid-19 Patients With Defined Hyperinflammation
Official title: A Phase-II Clinical Trial for First Line Treatment of Stage II/III Covid-19 Patients to Treat Hyperinflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid-19
Lead sponsor: University of Jena
Sponsor class: OTHER
First posted: 2020-04-08
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: single arm, non-randomized
Primary purpose: TREATMENT

Brief summary: RuxCoFlam is a single arm, non-randomized open phase II trial for front line treatment of Covid-19 patients with defined hyperinflammation.

Detailed description: RuxCoFlam is a single arm, non-randomized open phase II trial for front line treatment of Covid-19 patients with defined hyperinflammation. Purpose of the study is the reversal of hyperinflammation to improve pulmonary function, reduce respiratory dependency and reduce mortality. Patients with a hyperinflammation Score 10/16 without a clinical diagnosis of sepsis will be treated with 2 x 10mg Ruxolitinib with defined response adapted dose escalation up to 2 x 20mg for a duration of 7 days with clinical and/or radiographic response assessment. Inflammation assessment will be performed every other day (day 3, 5,7) using the CIS. In patients with unaffected CIS alteration \< 25% or increasing CIS \> 25% dose escalation by 5mg steps (15mg, day3; 20mg day 5) at the investigator´s discretion. Treatment can be extended up to 28 days if clinically indicated and the benefits of treatment outweigh the risks. Primary endpoint of the study is the overall response rate in reversal of hyperinflammation at day 7 compared to baseline. Secondary endpoints are total use of assisted oxygenation dependency (duration (days) of invasive/non-invasive ventilation or duration (days) of high-flow Oxygen support), radiologic response (reversal of pulmonary Covid-signs, Lung-XRay/CT), day 15 clinical status and day 15 and day 29 mortality. Patients aged ≥18 years hospitalized with COVID-19 pneumonia (demonstrated by CXRAY or chest CT), with a study specific Covid Inflammation Score ≥ 10 are eligible. Patients with active tuberculosis or uncontrolled bacterial, fungal, viral, or other infection (besides SARS-CoV-2 virus) will be excluded from the study.

Eligibility criteria: Inclusion Criteria:

* 1. Patient or guardian must provide written informed consent (and assent if applicable) before any study assessment is performed.
* 2. Male and female patients aged ≥ 18 years.
* 3. Patients with temperature \> 37.3°C
* 4. Patients with respiratory symptoms and/or hypoxia SpO2 \< 93%
* 5. Patients with Covid-19 stage II and stage III
* 6. Patients with lung imaging showing bi-pulmonary infiltrates (chest X-ray or CT scan).
* 7. Patients, with a Covid Inflammation Score ≥ 10

Exclusion Criteria:

* 1. History of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib.
* 2. Uncontrolled active bacterial, fungal, viral, or other infection (besides COVID-19).
* 3. Active Tuberculosis infection.
* 4. Known Positivity for HBV, HCV or HIV.
* 5. Patients who are on long-term use of oral anti-rejection or immunomodulatory drugs
* 6. Participating in any other interventional clinical trial for COVID-19.
* 7. Treatment with cytokine-directed agents such as anti-IL6 or anti-IL1R directed antibodies (i.e. tocilizumab, anakinra). Other treatment modalities used in locally adapted SOPs (corticosteroids, chloroquine, hydroxychloroquine, lopinavir-ritonavir) may be given with daily documentation of dose and schedule.
* 8. ALT or AST \> 5 x ULN detected within 24 hours at screening (according to local laboratory reference ranges).
* 9. ANC \< 500/µL at screening (according to local laboratory reference ranges).
* 10. Platelet count \< 50,000/µL at screening (according to local laboratory reference ranges).
* 11. Hemoglobin \< 6 g/dl (3.73mmol/l)
* 12. Pregnant or nursing (lactating) women.
* 13. Female patients of childbearing potential (e.g. are menstruating) and male patients who do not agree to abstinence or, if sexually active, do not agree to the use of highly effective contraception as defined below, throughout the study and for up to 90 days after stopping treatment, OR Female patients of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception as defined below, throughout the study and for up to 90 days after stopping treatment.

Highly effective contraception methods include:

* Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
* Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient.
* Use of oral, injected or implanted hormonal methods of contraception. Placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception (in case of oral contraception, patients should have been using the same pill on a stable dose for a minimum of 3 months before Screening).

Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

Primary outcomes:
measure: overall response rate in reversal of hyperinflammation
timeFrame: day 7 after start of therapy
Secondary outcomes:
Other outcomes:
Locations:
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera GmbH
city: Jena
country: Germany
facility: University Hospital Jena
city: Lübeck
country: Germany
facility: UKSH, Campus Lübeck
city: Stuttgart
country: Germany
facility: Klinikum der Landeshauptstadt Stuttgart gKöR
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH
Study officials:
affiliation: University Hospital Jena
name: Andreas Hochhaus, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: La Rosee F, Bremer HC, Gehrke I, Kehr A, Hochhaus A, Birndt S, Fellhauer M, Henkes M, Kumle B, Russo SG, La Rosee P. The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation. Leukemia. 2020 Jul;34(7):1805-1815. doi: 10.1038/s41375-020-0891-0. Epub 2020 Jun 9.