Clinical trial NCT05490888: Single and Multiple Dose Escalation of PHIN-214 in Child-Pugh A and B Liver Cirrhotics
Official title: A Phase 1 Open Label Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PHIN-214 in Adults With Child Pugh A and B Cirrhosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cirrhosis, Liver
Liver Fibrosis
Ascites Hepatic
Keywords: Terlipressin
Cirrhosis
Vasoconstrictor
Refractory Ascites
Lead sponsor: PharmaIN
Sponsor class: INDUSTRY
First posted: 2022-08-08
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This 2-part study will evaluate PHIN-214 given as a single one-time dose (Part 1) and in multiple doses (given as daily doses for 28-days) (in Part 2). Specifically, this study evaluates PHIN-214, to determine the safety, tolerability, and pharmacokinetic effects of PHIN-214, and to establish the maximum tolerated dose or optimal beneficial dose in patients with Child Pugh A and B Cirrhosis.

Detailed description: PHIN-214 action has similar actions as another medication called "terlipressin or TERLIVAZ®." Terlipressin has been shown to reduce portal hypertension, improve renal function, and induce natriuresis in cirrhotic patients with ascites without hepatorenal syndrome (HRS). It is approved in several countries including the US for the treatment of bleeding esophageal varices and HRS type 1 and is usually administered using multiple IV doses given by bolus injections in the hospital.

This study is an open label, first in human study of PHIN-214. PHIN-214 is a terlipressin derivative administered subcutaneously. It is a partial V1a agonist which is designed to reduce splanchnic blood pooling and portal hypertension. A resultant increase in systemic pressure and renal arterial pressure may increase kidney perfusion and creatinine clearance.

This study will evaluate a single dose of PHIN-214 (in Part 1) and in Part 2, daily doses of PHIN-214 for up to 28-days (called multiple ascending doses) of PHIN-214 to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of PHIN-214 in subjects with advanced cirrhosis.

Eligibility criteria: Key Inclusion Criteria:

1. History of cirrhosis based on histology or a combination of clinical, radiological, or biochemical assessment and classified as Child-Pugh A or B
2. Participants may be male or female aged 18 to 75 years.
3. Body mass index (BMI) within the range 18 to 40 kg/m2 (inclusive) at screening.
4. Female participants must be non-pregnant, non-lactating, or of non-childbearing potential or using highly efficient contraception for the full duration of the study

Key Exclusion Criteria:

1. Significant abnormalities in medical history or on physical examination, including: respiratory disease requiring therapy or history of respiratory failure, cardiovascular disease or hypertension, electrocardiogram abnormalities or history of significant EKG abnormalities.
2. History of diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, or any other disorder associated with fluid or sodium imbalance.
3. Significant kidney disease
4. Hepatic encephalopathy (HE) or altered mental status requiring hospitalization; variceal bleeding or upper gastrointestinal bleeding; or type 1 hepatorenal syndrome with acute kidney injury (HRS-AKI) during the previous 3 months prior to Screening.
5. Acute-on-chronic liver failure.
6. Recipient of a patent transjugular intrahepatic portosystemic shunt (TIPS).
7. Known positive HIV serology confirmed by HIV viral load.
8. Subjects with acute infections, including acute viral hepatitis (subjects with chronic hepatitis B are eligible if treatment regimen is stable ≥ 3 months prior to study inclusion).

Primary outcomes:
measure: maximum tolerated dose or optimal beneficial dose of PHIN-214 in multiple ascending dose; safety and tolerability.
timeFrame: may be up to six weeks
measure: Pharmacokinetics of PHIN-214
timeFrame: up to six weeks
measure: Pharmacokinetics of PHIN-214 metabolite
timeFrame: up to six weeks
Secondary outcomes:
measure: Immunogenicity of PHIN-214
timeFrame: up to six weeks
Other outcomes:
measure: Blood pressure
timeFrame: up to six weeks
measure: Heart rate
timeFrame: up to six weeks
measure: 12-lead ECG
timeFrame: up to six weeks
measure: Oxygenation level
timeFrame: up to six weeks
Locations:
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Methodist Health System, Dallas Medical Center
state: Texas
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
Study officials:
affiliation: PharmaIN
name: Cynthia C Jones
role: STUDY_CHAIR
References: