Randomized adaptive assessment of post COVID syndrome treatments (RAPID) Reducing Inflammatory Activity in Patients with post COVID Syndrome (REVIVE)

Prior treatment

• Ongoing SARS-CoV-2 infection or positive test for SARS-CoV-2 within 14 days prior to enrolment
• Participation in any other interventional clinical trial within the last 30 days before the start of this trial
• Prior use of IMU-838 or a drug prescribed to treat COVID-19 within 30 days prior to enrollment in the study.
• Vaccination for COVID-19 within 28 days prior to enrollment, or other vaccines (influenza, shingles, etc.) within 14 days of enrollment, or planned use of any vaccine until Day 84
• Any concomitant disease impairing efficacy endpoint analysis, in the opinion of the investigator
• Any use of the following concomitant medications is prohibited during Screening: - Any medication known to significantly increase urinary elimination of uric acid, in particular lesinurad, as well as uricosuric drugs such as probenecid - Treatments for any malignancy, in particular irinotecan, paclitaxel, tretinoin, bosutinib, sorafinib, enasidenib, erlotinib, regorafenib, pazopanib, and nilotinib - Any drug significantly restricting water diuresis, in particular vasopressin and vasopressin analogs - Current use of statins - Methotrexate at doses of > 17.5 mg/week
• Previous participation in this trial
• Known or persistent abuse of medication, drugs, or alcohol
• Known history of nephrolithiasis or underlying condition with a strong association of nephrolithiasis, including hereditary hyperoxaluria or hereditary hyperuricemia. As an exception, patients with a history of a singular period of nephrolithiasis who have been symptom free within the last 3 years prior to the screening visit and whose stones were not composed of uric acid or oxalate, may be included.
• History of medically significant active, chronic systemic infections (not considering the SARS-CoV-2 infection) within 6 months before Day 1, including, but not limited to tuberculosis, hepatitis B, C or D, and human immunodeficiency virus (HIV)

Other illness

• Pre-COVID history of chronic fatigue syndrome or other fatigue syndromes that are due to associated diseases (e.g., cancer, autoimmune diseases)
• Known or suspected Gilbert syndrome (Morbus Meulengracht)
• Hypersensitivity to the active substance or to any of the excipients
• Severe impairment of liver function (Child Pugh class C)
• Evidence of currently active malignancy (defined as evidence of primary tumor or metastases) of any organ system (other than localized basal cell carcinoma of the skin or adequately treated cervical cancer), independent of treatment status.
• Presence of serious heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, or uncontrolled congestive heart failure (New York Heart Association [NYHA] class 3 or 4)
• Active major medical or psychiatric illness which cannot be controlled by medication (e.g., severe depression, schizophrenia, psychotic disorder), history of suicide attempt, or current suicidal ideation, if any of those conditions in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol

Lab values

• Presence of the following laboratory values at Screening - Platelet count <100,000/mm³ (<100 x 109/L) - Neutrophil count <1,500/mm³ (1.5 x 109/L) - Serum creatinine >1.5 x upper limit of normal (ULN) - Total bilirubin, GOT, GPT, or gGPT >1.5 x ULN - Serum uric acid levels >1.2 x ULN - Indirect (unconjugated) bilirubin >1.2 x ULN

Other

• Known or planned pregnancy; nursing period
• Simultaneous participation in other interventional trials which could interfere with this trial (simultaneous participation in registry and diagnostic trials is allowed)
• Patient without legal capacity who is unable to understand the nature, significance, and consequences of the trial
• Person who is in a relationship of dependence/employment with the sponsor or the investigator
• Persons deprived of liberty or placed in an institution by judicial or administrative order
• History or clinical diagnosis of gout

• Male or female patients ≥18 years of age
• Ability to provide and use a smartphone, tablet or other device for download and installation of the medical device software used in the trial
• Willingness to not connect medical devices used in this trial to any other app that is not defined in this protocol, especially not to Garmin Connect
• Willingness to abstain from changes in the type, dosage, and frequency of concomitant medications through Day 84
• Proof of an index COVID-19 infection by positive COVID-19 PCR/antigen test or written confirmation by the investigator using a pre-specified form that confirms the COVID-19 infection.
• Use of a highly effective method of contraception correctly and consistently, as applicable, during trial treatment and for 30 days after the final dose (applicable to individuals of childbearing potential and participating men whose partners may become pregnant)
• Female patients of childbearing potential, must have a negative pregnancy test (at Screening-V1 (blood test; see Tab. 1) and before the first IMP intake (Day 1 urine test) AND agreement of not to attempt to become pregnant AND agreement of not to donate ova AND usage of highly effective forms of birth control (as defined by Recommendations related to contraception and pregnancy testing in clinical trials- Heads of Medicines Agencies (HMA); see 20.1)
• Male patients must agree not to father a child or to donate sperm starting at Screening-V1, throughout the clinical study, and for 30 days after the last intake of the IMP. Male patients must also: a. abstain from sexual intercourse with a female partner (acceptable only if it is the patient’s usual form of birth control/lifestyle choice), or b. use adequate barrier contraception during treatment with the IMP and until at least 30 days after the last intake of the IMP, and c. if they have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined above d. if they have a pregnant partner, they must use condoms while taking the IMP to avoid exposure of the fetus to the IMP.
• Symptoms consistent with PCS that began within 4 weeks of the index infection and persisted for >12 weeks. The identified symptoms of PCS cannot be attributed to other intervening diagnoses or medications and did not exist prior to the acute COVID preceding PCS.
• Moderate to severe overall disability, defined as a Bell Scale of 20-60
• ≥2 of the following post-COVID symptoms, defined as: a. fatigue, defined as an FSS score ≥36 b. cognitive impairment, defined as a MoCA score between 10 – 25 c. shortness of breath, defined as a mMRC ≥2 d. Postural Orthostatic Tachycardia Syndrome (POTS), defined as the following results in the PST: i. a sustained heart rate increase of ≥30 bpm within 10 min. of standing and/or a heart rate reaching >120 bpm within 10 min. of standing and ii. absence of a sustained 20 mmHg decrease in systolic blood pressure within 10 min. of standing Sustained is defined as ≥2 sequential measurements during the standing phase of the PST. If the diagnosis of POTS should have been established and treatment initiated prior to the screening visit, the results of the PST cannot be considered meaningful. In this case, the fulfilment of the inclusion criterion can be confirmed by the investigator by filling out a prespecified form that confirms the establishment of the diagnosis of POTS prior to screening. The concomitant medication must be specified in the eCRF.
• Written informed consent obtained according to international guidelines and local laws
• Ability to understand the nature of the trial and the trial related procedures and to comply with them