Clinical Trials

CRV431

A Study in Healthy Volunteers and Patients With Chronic Hepatitis B (ClinicalTrials.gov Identifier: NCT03596697)

Overview

Title: A Randomized, Partially-blinded, Placebo-controlled, Ascending Sequential Dose Groups, Single Dose Study of the Safety, Tolerability and Pharmacokinetics of CRV431, Alone and In Combination With Tenofovir Disoproxil Fumarate in Healthy Subjects, With a Pilot Study of Multiple Ascending Sequential Doses in HBV-Infected Subjects on Chronic Tenofovir Disoproxil Fumarate Treatment

Condition: Infectious Disease

Interventions: CRV431, Placebo, TDF (Viread®)

Objectives

Part 1: To assess the safety, tolerability, and PK of a single dose of CRV431 in healthy volunteers

Part 2: Single dose drug-drug interaction study in healthy volunteers with CRV431 co-treated with TDF

Part 3: A multiple ascending dose study of CRV431 administered daily for 28 days in virally suppressed HBV-infected patients; one of the dosing cohorts will include patients with moderate liver fibrosis; the primary purpose of this study is to evaluate safety, tolerability and pharmacokinetics following multiple doses of CRV431; although this is only a 28-day study, analysis of certain biomarkers will be included to evaluate efficacy signals

Outcomes

  • Parts 1 and 2 trials completed successfully
  • Part 3 has not yet been completed
  • The collective data from the Parts 1 and 2 demonstrate a favorable pharmacological, pharmacokinetic, and safety profile for CRV431
  • Clinical findings to date support the proposed further clinical development program of CRV431

TXL

A Multiple Ascending Dose Proof of Concept Study (ClinicalTrials.gov Identifier: NCT02710604)

Overview

Title: A Phase 2, Randomized, Open-label, Ascending, Sequential Dose Group, Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of TXL in HBV-infected Subjects

Condition: Infectious Disease

Interventions: TXL; TDF (Viread®)

Objectives

Primary Objective: To evaluate the safety and tolerability of multiple oral (PO) doses of TXL at multiple ascending dose levels; to evaluate the antiviral activity of TXL versus Tenofovir disproxil fumarate (TDF; Viread)

Secondary Objective: To evaluate the pharmacokinetics (PK) of multiple doses of TXL at multiple dose levels in a fasted state

Outcomes

  • Trial completed successfully
  • TXL was safe and well tolerated when orally administered to HBV-infected fasting subjects at all doses tested over a duration of 28 days
  • Systemic exposures for TXL and TFV in fasted subjects increased with escalating TXL doses for both single and repeated daily oral doses
  • Viral load reductions observed with 50 mg and 100 mg TXL were comparable to those observed with TDF 300 mg
  • Lower systemic TFV exposures after TXL dosing may reduce the risk of developing bone and kidney toxicities that have been reported for TDF

TXL

A Multiple Dose Study of the Safety, Tolerability and PK of TXL in Healthy Subjects (ClinicalTrials.gov Identifier: NCT02585440)

Overview

Title: A Phase 1, Randomized, Partial-Blind, Placebo-controlled, Sequential Dose Group, Ascending, Multiple Dose Study of the Safety, Tolerability and Pharmacokinetics, With Food Effect, of TXL in Healthy Subjects

Condition: Infectious Disease

Interventions: TXL; Placebo

Objectives

Primary Objective: To evaluate the safety and tolerability of multiple oral (PO) doses of TXL at increasing dose levels

Secondary Objective: To evaluate the pharmacokinetics of multiple doses of TXL at increasing dose levels, in a fasted state; to evaluate the pharmacokinetics of a single dose of TXL 50 mg in a fed state

Outcomes

  • Trial completed successfully
  • Multiple formulations of TXL were safe and well tolerated when administered to fasted or fed healthy volunteers
  • Prototype formulations altered TXL exposures

TXL

Evaluation of Effect of Renal Impairment on the PK of Tenofovir Exalidex (ClinicalTrials.gov Identifier: NCT03284164)

Overview

Title: An Open-Label Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics of Tenofovir Exalidex

Condition: Infectious Disease

Interventions: TXL

Objectives

Primary Objective

  • Objective 1: To compare the plasma PK of TXL and its metabolite TFV following administration of TXL in subjects with severe renal impairment (RI) to those of healthy matched control subjects
  • Objective 2: To compare the urine PK of TXL and its metabolite TFV following administration of TXL in subjects with severe RI to those of healthy matched control subjects

Secondary Objective

  • To evaluate the safety and tolerability of TXL in subjects with severe RI

Outcomes

  • Trial completed successfully
  • Dosage adjustment is not needed for subjects with severe RI receiving TXL
  • TXL administration to subjects with severe RI was safe and well-tolerated