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    The EU Clinical Trials Register currently displays   42556   clinical trials with a EudraCT protocol, of which   7007   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2020-002295-13
    Sponsor's Protocol Code Number:APHP200552
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-05-22
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2020-002295-13
    A.3Full title of the trial
    Evaluation of the efficacy, safety and tolerability of alisporivir for the treatment of hospitalised patients with infections due to SARS-CoV-2 (COVID-19).
    A randomised, open-label, proof of concept, Phase 2 study.
    Evaluation de l’efficacité, la sécurité et la tolérance de l'alisporivir chez des patients hospitalisés pour une infection par le SARS- CoV-2 (COVID-19).
    Étude de faisabilité de phase 2, randomisée, en ouvert.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Evaluation of the efficacy, safety and tolerability of alisporivir for the treatment of hospitalised patients with infections due to SARS-CoV-2 (COVID-19).
    Evaluation l’efficacité, la sécurité et la tolérance de l'alisporivir chez des patients hospitalisés pour une infection par le SARS- CoV-2 (COVID-19).
    A.3.2Name or abbreviated title of the trial where available
    CYCLOVID
    A.4.1Sponsor's protocol code numberAPHP200552
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAssistance Publique - Hôpitaux Paris
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportDEBIOPHARM SA
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAssistance Publique - Hôpitaux Paris
    B.5.2Functional name of contact pointProject Manager
    B.5.3 Address:
    B.5.3.1Street Address1, av Claude Vellefaux
    B.5.3.2Town/ cityParis
    B.5.3.3Post code75010
    B.5.3.4CountryFrance
    B.5.4Telephone number+330144841747
    B.5.5Fax number+330144841701
    B.5.6E-mailcandy.estevez@aphp.fr
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namealisporivir
    D.3.2Product code ALV, DEB025
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    Nasogastric use (Noncurrent)
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    The study population will consist of adults (18-80 years old) hospitalised for ≤48 hours prior to randomisation with a diagnosis of COVID-19 based on symptoms onset and SARS-CoV-2 RT-PCR test positive from nasopharyngeal swab. Patients with ARDS or patients requiring mechanical ventilation at screening or randomisation will be excluded
    E.1.1.1Medical condition in easily understood language
    Adults hospitalised with a diagnosis of COVID-19.
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10051905
    E.1.2Term Coronavirus infection
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to evaluate the reduction in SARS-CoV-2 viral load in nasopharyngeal swabs at D7 in patients hospitalised for COVID19 and treated either with alisporivir and SOC or SOC alone.
    E.2.2Secondary objectives of the trial
    The secondary objective is to evaluate the clinical and radiological efficacy, safety and tolerability of alisporivir plus SOC compared to SOC alone in patients with COVID-19.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    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.
    E.4Principal exclusion criteria
    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.
    E.5 End points
    E.5.1Primary end point(s)
    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
    E.5.1.1Timepoint(s) of evaluation of this end point
    Timeframe/Time Point : D1 directly after randomisation (for Arm 1 before the first alisporivir administration) and D7
    E.5.2Secondary end point(s)
    Percentages of patients negative for SARS CoV 2 RNA in nasopharyngeal swabs at D14 (EOT) and FUP visits in the two treatment arms.
    Time to negative viral load
    Time to resolution of symptoms
    Duration of need for supplemental oxygen
    Duration of hospitalisation - measured in days.
    Duration of new non-invasive ventilation or high flow oxygen use
    Duration of new oxygen use
    Duration of new ventilator or ECMO use
    Number of non-invasive ventilation/high flow oxygen free days
    Number of oxygenation free days
    Patient all-cause mortality at D14 (EOT visit), at D28 (FUP14), at D90 (EOS): Date and cause of death (if applicable).
    Safety:
    Cumulative incidence of any AE
    Cumulative incidence of Grade 3 and 4 AEs
    Cumulative incidence of SAEs
    E.5.2.1Timepoint(s) of evaluation of this end point
    EOT, FUP7 and D28 ± 2 days
    D1 to D28 ± 2 days
    D1 to D28 ± 2 days and to D90± 2 days
    D1 to D28 ± 2 days and to D90± 2 days
    D1 to D28 ± 2 days and to D90± 2 days
    D1 to D28 ± 2 days and to D90± 2 days
    D1 to D28 ± 2 days and to D90± 2 days
    D1 to D28 ± 2 days and to D90± 2 days
    D1 to D28 ± 2 days and to D90± 2 days
    D1 to D28 ± 2 days and to D90± 2 days
    D1 to EOT, and to D28 ± 2 days, and to D90± 2 days
    D1 to D90 ± 2 days
    D1 to D90 ± 2 days
    D1 to D90 ± 2 days
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    SOC
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days4
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state100
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-10-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-26
    P. End of Trial
    P.End of Trial StatusOngoing
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