COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002295-13/FR

Assistance Publique - Hôpitaux Paris - Project Manager

candy.estevez@aphp.fr

2020-05-22

RCT

Randomized

Parallel

Open label

multi-center

Treatment

1. Adult males and females ≥18 years and ≤80 years of age at the time of screening. 2. Are hospitalised during the screening period with duration of hospitalisation prior to randomisation ≤48 hours. 3. Have a diagnosis of COVID-19 based on symptoms onset and SARS-CoV-2 RT-PCR test positive from nasopharyngeal swab. 4. Have at least one (1) of the following: a. Radiographic pulmonary infiltrates (CT scan), AND/OR b. Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤94% on room air, AND/OR c. Requirement of supplemental oxygen. 5. If female, of non-childbearing potential (e.g. post-menopausal as demonstrated by FSH or surgical sterilization i.e., tubal ligation or hysterectomy), or if of childbearing potential, be willing to commit to either sexual abstinence or use of at least 2 medically accepted, effective methods of birth control (e.g., condom, spermicidal gel, oral contraceptive, indwelling intrauterine device, hormonal implant/patch, injections, approved cervical ring) from screening through 7 months after last alisporivir dose. 6. If male, a willingness to refrain from donating sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, a willingness to use a condom in addition to having the female partner use a highly effective method of birth control (such as an intrauterine device, diaphragm, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation) from screening through 4 months after last alisporivir dose. 7. Willing and able to provide written informed consent. 8. Willing to comply with all study assessments and adhere to the protocol schedule. 9. Has an affiliation with a social security system.

1. Patients with ARDS or patients requiring mechanical ventilation at screening or randomisation. 2. In the opinion of the investigator, the patient is unlikely to survive the following 7 days after randomisation due to a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock. 3. Patients who are unconscious or considered by the investigator unable to consent. 4. Other severe co-morbidity with life expectancy ≤3 months according to the investigator’s assessment. 5. Critically ill patients who have an APACHE II score ≥30. 6. Concomitant severe bacterial infection including blood stream infections, endocarditis, osteomyelitis, retroperitoneal abscess, septic arthritis, or meningitis diagnosed within 7 days prior to randomisation (bacterial pulmonary infection that may complicate COVID-19 is not an exclusion criterion). 7. Any of the following signs of severe sepsis: a. Shock or profound hypotension defined as systolic blood pressure ≤90 mm Hg or a decrease of ≥40 mm Hg from the value obtained during screening (if more than one measurement is taken) that is not responsive to fluid challenge. b. Hypothermia (core temperature ≤ 35.6°C). c. DIC as evidenced by PT, PTT 2 × ULN, or platelets ≤ 50% of the LLN. 8. History of positive test for HIV including all patients currently on HAART regardless of the CD4+ cell count. 9. Presence of immunodeficiency or an immunocompromised condition including neutropenia (≤1,000 neutrophils/mm3 obtained from the local laboratory at screening), haematologic malignancy, history of haematopoietic stem cell transplant, history of solid organ transplant, receiving immunosuppressive therapy (e.g. cancer chemotherapy, mAbs for autoimmune disease, or medications to prevent transplant rejection), and long term use of systemic corticosteroids (e.g., ≥20 mg/day of prednisone or systemic equivalent for at least 2 weeks). 10. Severe hepatic impairment at screening, as evidenced by ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN (except in case of known Gilbert syndrome), or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy). 11. Acute hepatitis, cirrhosis (any Child-Pugh class), acute hepatic failure or acute decompensation of chronic hepatic failure. 12. Alkaline phosphatase ≥3.0 × ULN. Patients with values ≥3.0 × ULN and ≤5.0 × ULN are eligible if this value is documented to be acute and directly related to the infectious process being treated. 13. Severe renal impairment (creatinine-clearance ≤30 mL/min) or ESRD requiring haemodialysis or peritoneal dialysis, according to Cockcroft-Gault. 14. Uncontrolled hypertension (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg). 15. Uncontrolled thyroid function (TSH, free T3 or free T4 outside of normal ranges). 16. History of known or suspected Clostridium difficile infection. 17. History of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures). 18. Acute co-morbidity within 7 days before inclusion such as myocardial infarction. 19. A female who is pregnant or breastfeeding. 20. Documented hypersensitivity reaction or anaphylaxis to alisporivir, one of the non-active ingredients or any of the SOC medications. 21. Receipt of any investigational medication in the 3 months prior to screening. 22. Anticipated transfer to another hospital that is not a study site during the first 4 days of treatment. 23. Patients previously treated with antivirals, immunomodulators (mAbs in the 3 months prior to screening) and other medicines prohibited in this study (see Section 18.7) in the 14 days prior to randomisation. 24. Ongoing or recent use of any other medication (including over the counter medication and herbal products) within 14 days before randomisation or within 5 drug half-lives of that medication (whichever is longer) that are known inhibitors/inducers of cytochrome P450 3A or P-gp, or inhibitors of OATPs, MRP2 or BSEP (see Section 18.7). Known need of concomitant treatment with the following medications during treatment with alisporivir and 14 days after the end of treatment: a. Known inhibitors/inducers of cytochrome P450 3A or P-gp, or inhibitors of OATPs, MRP2 or BSEP, b. Drugs with narrow therapeutic index that are known sensitive substrates of cytochrome P450 3A, or substrates of P-gp, OATPs, MRP2 or BSEP. 25. Any other condition or prior therapy, which, in the opinion of the investigator, would make the patient unsuitable for this study, including those that would prevent compliance with all study assessments and adherence to the protocol schedule. 26. Patients with history of pancreatic disease. 27. Patients under legal protection. 28. Prisoners. 29. Patients participating in another interventional study.

2

Assistance Publique - Hôpitaux Paris

18

100

France

Moderate/severe disease at enrollment

4: Moderate/severe disease at enrollment

100

The endpoint of the primary objective 'to evaluate the reduction in SARS-CoV-2 viral load in nasopharyngeal swabs at D7 in patients hospitalized for COVID-19 and treated either with alisporivir and SOC or SOC alone' is presented in Table 4 1. Viral load in cells taken from nasopharyngeal swabs will be measured using the RT-PCR COVID 19 test based on droplet digital PCR, a method allowing for normalization to the cell content in the sample. Endpoint : VLRR, defined as the proportion of patients with an intra patient decrease of ≥ 1.5 log10 viral load, at D7 compared to Baseline

Declared number of arm (2.0) differs from found arms (1.0)

Phase 2

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