Evaluation of Alisporivir for the Treatment of Hospitalised Patients With Infections Due to SARS-CoV-2 (COVID-19)
Last updated on July 2021Recruitment
- Recruitment Status
- Not yet recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- Sars Cov 2
- Type
- Interventional
- Phase
- Phase 2
- Design
- Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: 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-2Masking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 80 years
- Gender
- Both males and females
Description
Cyclophilins are cellular (host) peptidyl-prolyl cis/trans isomerases (molecular chaperones) involved in protein folding, maturation, and trafficking. Cyclophilins have been shown to play a key role in the lifecycle of many coronaviruses, including human coronaviruses 229E (HCoV-229E) and NL-63 (HCo...
Cyclophilins are cellular (host) peptidyl-prolyl cis/trans isomerases (molecular chaperones) involved in protein folding, maturation, and trafficking. Cyclophilins have been shown to play a key role in the lifecycle of many coronaviruses, including human coronaviruses 229E (HCoV-229E) and NL-63 (HCoV-NL63), feline infectious peritonitis coronavirus (FPIV), SARS-CoV and Middle-East-Respiratory-Syndrome coronavirus (MERS-CoV). Cyclosporin A (CsA), a potent cyclophilin inhibitor, blocks the replication of various coronaviruses in vitro, including HCoV-229E, HCoV-NL63, FPIV, mouse hepatitis virus (MHV), avian infectious bronchitis virus, and SARS-CoV. Alisporivir is a non-immunosuppressive analogue of CsA with potent cyclophilin inhibition properties. In vitro, alisporivir inhibits the replication of HCoV-229E, HCoV-NL63, MHV, SARS-CoV and MERS-CoV at low micromolar concentrations without cytotoxic effect. Although alisporivir has not demonstrated activity against coronaviruses in in vivo models to date, recent experiments showed that alisporivir bears concentration-dependent properties against CoV-2 in vitro. Preclinical pharmacology data indicate that, after oral administration, alisporivir is widely distributed in the whole body, including the lungs. Furthermore, the EC90 of alisporivir against SARS-CoV-2 in VeroE6 cells appears to be clinically achievable in patients. In addition, because alisporivir inhibits all cellular cyclophilins, it also blocks mitochondrial cyclophilin-D, a key regulator of mitochondrial permeability transition pore (mPTP) opening, a mechanism involved in triggering cell death. Therefore, besides its antiviral properties, alisporivir may also be effective in preventing lung tissue damage.
Tracking Information
- NCT #
- NCT04608214
- Collaborators
- Debiopharm International SA
- Investigators
- Principal Investigator: Jean-Michel PAWLOTSKY, MD, PhD Assistance Publique Hôpitaux de Paris (AP-HP)
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