Evaluation of Alisporivir for the Treatment of Hospitalised Patients With Infections Due to SARS-CoV-2 (COVID-19)

NCT04608214 | Completed Phase 2 DMC

• 2 other identifiers: APHP2005522020-002295-13
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

COVID-19 is a viral respiratory and systemic disease that has been rapidly spreading globally since the first cases were reported in December 2019 and has now become pandemic. The causative agent of COVID-19 was identified as a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, first designated as 2019-nCoV). The disease manifestations of COVID-19 can range from mild, self-resolving respiratory disease to severe pneumonia, ARDS, multiorgan failure, and ultimately death. In early reports, the mortality rate among patients admitted to hospital and with confirmed SARS-CoV-2 infection was reported to be between 4 and 15%. Although the disease can afflict all age groups, elderly patients and patients with underlying comorbidities such as high body mass index, hypertension, diabetes, cardiovascular disease, or cerebrovascular disease are at risk of developing severe disease and dying. There are currently no etiologic treatments for COVID-19, and efforts are underway to identify therapeutics that could be effective in controlling this disease.

Conditions

SARS-CoV-2

Keywords

Alisporivir; Viral Load; efficacy; safety; tolerability

Outcome Measures

Primary Outcomes (1)

• Change in SARS-CoV-2 viral load in nasopharyngeal swabs

  at Day 1 and Day 7

Secondary Outcomes (33)

• Viral Load Response Rate (VLRR)

  at Day 1 and Day 7

• Percentage of patients reporting each severity rating on an 8-point ordinal scale.

  at Day 1, Day4, Day 7, Day 11, Day 14 and Day 90

• Change in National Early Warning Score scale

  at Day 1, Day 4, Day 7, Day 11, Day 14 and Day 90

• Changes in thoracic CT scan

  screening to Day 1, Day 14 and Day 90

• Percentage of patients admitted to Intensive Care Unit (ICU)

  at Day 1 to Day 28

Study Arms (2)

Alisporivir

EXPERIMENTAL

Administration of alisporivir and standard of care (SOC)

Drug: Alisporivir

Standard of care (SOC)

ACTIVE COMPARATOR

Locally accepted regimen protocols for patient care

Other: Standard of care (SOC)

Interventions

Alisporivir DRUG

Administration of alisporivir at the dose of 600 mg p.o. BID from D1 to D14 to patients and standard of care (SOC).

Alisporivir

Standard of care (SOC) OTHER

Locally accepted regimen protocols for patient care and select agents based on the underlying diagnosis and the severity of COVID 19 (excepting e.g. azithromycin and other antibiotics listed as prohibited medications)

Standard of care (SOC)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males and females ≥18 years and ≤80 years of age at the time of screening.
• Are hospitalised during the screening period with duration of hospitalisation prior to randomisation ≤48 hours.
• Have a diagnosis of COVID-19 based on symptoms onset and positive SARS-CoV-2 RT-PCR test from nasopharyngeal swab.
• Viral load ≤ 30 Ct
• Have at least one (1) of the following:
• Radiographic pulmonary infiltrates (CT scan), AND/OR
• Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤94% on room air, AND/OR
• Requirement for supplemental oxygen.
• If female, of non-childbearing potential 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 from screening through 2 months after last alisporivir dose.
• 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 from screening through 4 months after last alisporivir dose.
• Willing and able to provide written informed consent.
• Willing to comply with all study assessments and adhere to the protocol schedule.
• Has an affiliation with a social security system.

You may not qualify if:

• Patients requiring mechanical ventilation at screening or randomisation.
• 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.
• Patients who are unconscious or considered by the investigator unable to consent.
• Other severe co-morbidity with life expectancy ≤3 months according to the investigator's assessment.
• Critically ill patients who have an APACHE II score ≥30.
• Any of the following signs of severe sepsis:
• 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 that is not responsive to fluid challenge.
• Hypothermia (core temperature ≤ 35.6°C).
• Disseminated intravascular coagulation (DIC) as evidenced by PT, PTT 2 × upper limit of normal (ULN), or platelets ≤ 50% of the lower limit of normal (LLN).
• History of positive test for human immunodeficiency virus (HIV) including all patients currently on highly active antiretroviral therapy (HAART) regardless of the CD4+ cell count.
• Presence of immunodeficiency or an immunocompromised condition including neutropenia, haematologic malignancy, history of haematopoietic stem cell transplant, history of solid organ transplant, receiving immunosuppressive therapy and long term use of systemic corticosteroids.
• Severe hepatic impairment at screening, as evidenced by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 5 × ULN or total bilirubin ≥2 × ULN (except in case of known Gilbert syndrome), or clinical signs of decompensated cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy).
• Acute hepatitis, decompensated cirrhosis (any Child-Pugh B or C class), acute hepatic failure or acute decompensation of chronic hepatic failure.
• Severe renal impairment (creatinine-clearance ≤30 mL/min) or end-stage renal disease (ESRD) requiring haemodialysis or peritoneal dialysis, according to Cockcroft-Gault.
• Uncontrolled hypertension that is not responsive to treatment.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Debiopharm International SA: collaborator

Study Sites (1)

Assistance Publique Hôpitaux de Paris - CHU Henri Mondor

Créteil, France

Location

MeSH Terms

Interventions

alisporivir; Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Jean-Michel PAWLOTSKY, MD, PhD

  Assistance Publique Hôpitaux de Paris (AP-HP)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomised, open-label, proof of-concept, Phase 2 study to evaluate the efficacy, safety and tolerability of alisporivir plus SOC as compared to SOC for the treatment of hospitalised patients with infections due to SARS-CoV-2

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 29, 2020
• Study Start: January 8, 2021
• Primary Completion: January 19, 2022
• Study Completion: April 13, 2022
• Last Updated: May 11, 2023

Record last verified: 2023-04

Locations

FR (1)