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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Goethe University Frankfurt

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Virus Diseases [C02]

Trial duration

18 Jul 2024 → 30 Sep 2025

Decision date (initial)

2024-05-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bundesministerium für Bildung und Forschung (BMBF)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Compare the impact of PCS treatment with IMU-838 to control on patient overall physical function at Day 56.

Secondary objectives 4

1. Compare the impact of PCS treatment with IMU-838 to control on patient overall mental and physical health at Days 28, 56 and 84
2. Compare the impact of PCS treatment with IMU-838 to control on patient- and physician-reported outcomes measuring key PCS neuropsychiatric symptoms
3. Compare the impact of PCS treatment with IMU-838 to control on patient- and physician-reported outcomes measuring key physical PCS symptoms
4. Compare the impact of PCS treatment with IMU-838 to control on autonomic function and physical activity parameters

Conditions and MedDRA coding

Post Covid Syndrome (PCS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Male or female patients ≥18 years of age
2. 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)
3. 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)
4. 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.
5. 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.
6. Moderate to severe overall disability, defined as a Bell Scale of 20-60
7. ≥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.
8. Written informed consent obtained according to international guidelines and local laws
9. Ability to understand the nature of the trial and the trial related procedures and to comply with them
10. Ability to provide and use a smartphone, tablet or other device for download and installation of the medical device software used in the trial
11. 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
12. Willingness to abstain from changes in the type, dosage, and frequency of concomitant medications through Day 84
13. 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.

Exclusion criteria 24

1. Known or planned pregnancy; nursing period
2. Known or suspected Gilbert syndrome (Morbus Meulengracht)
3. Severe impairment of liver function (Child Pugh class C)
4. 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.
5. History or clinical diagnosis of gout
6. 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.
7. 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)
8. 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)
9. 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
10. Ongoing SARS-CoV-2 infection or positive test for SARS-CoV-2 within 14 days prior to enrolment
11. Pre-COVID history of chronic fatigue syndrome or other fatigue syndromes that are due to associated diseases (e.g., cancer, autoimmune diseases)
12. Participation in any other interventional clinical trial within the last 30 days before the start of this trial
13. Prior use of IMU-838 or a drug prescribed to treat COVID-19 within 30 days prior to enrollment in the study.
14. 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
15. Any concomitant disease impairing efficacy endpoint analysis, in the opinion of the investigator
16. 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
17. Simultaneous participation in other interventional trials which could interfere with this trial (simultaneous participation in registry and diagnostic trials is allowed)
18. Patient without legal capacity who is unable to understand the nature, significance, and consequences of the trial
19. Previous participation in this trial
20. Known or persistent abuse of medication, drugs, or alcohol
21. Person who is in a relationship of dependence/employment with the sponsor or the investigator
22. Persons deprived of liberty or placed in an institution by judicial or administrative order
23. 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
24. Hypersensitivity to the active substance or to any of the excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Intra-patient change in physical function as measured by the Short Form-36 Physical Function (SF-36-PF) from Baseline to Day 56

Secondary endpoints 5

1. Intra-patient change in overall mental and physical health as measured by the SF-36-PF; from Baseline to Days 28, 56 and 84
2. Intra-patient change from Baseline to Days 28, 56 and 84 in a. Intensity of fatigue and incapacitation measured by the FSS b. Severity of mental disorder symptoms such as depression, anxiety, somatization, and distress measured by the PHQ modules PHQ-9, GAD-7, PHQ-15, and PHQ-stress
3. Intra-patient change from Baseline to Days 28 and 56 in Cognitive function measured by the MoCa
4. Intra-patient change from Baseline to Days 28, 56 and 84 in a. Severity of dyspnea, measured by the mMRC b. PEM frequency, strength and severity as measured by the PEM questionnaire c. Intra-patient change from Baseline to Days 28 and 56 in orthostatic/autonomic dysfunction measured by the PST d. Physical exercise capacity, measured as the change in number of repetitions during the 1MSTST
5. Intra-patient change from Baseline to Days 28 and 56 in a. Physical activity parameters: global activity (steps/24h), wear time (min), time spent in physical activity (min), resting (bpm) and activity heart rate bpm) b. Autonomic function parameters: heart rate turbulence, nocturnal heart rate, nocturnal respiratory rate, expiration-triggered sinus arrhythmia, baroreflex sensitivity, frequency of spontaneous ectopic beats measured by use of mhealth devices

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Goethe University Frankfurt

Sponsor organisation

Goethe University Frankfurt

Address

Theodor-Stern-Kai 7

City

Frankfurt Am Main

Postcode

60590

Country

Germany

Scientific contact point

Organisation

Goethe University Frankfurt

Contact name

Prof. Dr. Maria Vehreschild

Public contact point

Organisation

Goethe University Frankfurt

Contact name

Goether University Frankfurt

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications