Single and Multiple Dose Escalation of PHIN-214 in Child-Pugh A and B Liver Cirrhotics

September 3, 2025 updated by: PharmaIN

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

74

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Recruiting
        • Arizona Liver Health
        • Contact:
    • California
      • Coronado, California, United States, 92118
        • Recruiting
        • Southern California Research Center
        • Contact:
    • Louisiana
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
    • Pennsylvania
    • Texas
      • Dallas, Texas, United States, 75216
        • Recruiting
        • VA North Texas Healthcare System
        • Contact:
        • Principal Investigator:
          • Jacqueline O'Leary, MD
      • Dallas, Texas, United States, 75203
        • Recruiting
        • Methodist Health System, Dallas Medical Center
        • Contact:
      • San Antonio, Texas, United States, 78215
        • Recruiting
        • Texas Liver Institute
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: single dose of PHIN-214
Participants in Part 1 will receive one dose of PHIN-214 administered subcutaneously. Dose level will be assigned in ascending doses to observe initial safety and tolerability. A Safety Committee will review information from each patient and determine the dose level for the subsequent participants.
Drug: PHIN-214 Subcutaneous injection
subcutaneous injection(s) with PHIN-214 terlipressin derivative
Other Names:
  • Terlipressin derivative
Experimental: multiple daily dosing of PHIN-214
Participants in Part 2 will be trained to give themselves a daily dose of PHIN-214 at home by subcutaneous injection for 28-days. The dose level assigned to each participant will be determined by a Safety Committee after reviewing information from the last participants' experience and compilation of experiences on all previous participants. Dose level advancement will be guided throughout the study by the experiences and information collected from each participant.
Drug: PHIN-214 Subcutaneous injection
subcutaneous injection(s) with PHIN-214 terlipressin derivative
Other Names:
  • Terlipressin derivative

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
maximum tolerated dose or optimal beneficial dose of PHIN-214 in multiple ascending dose; safety and tolerability.
Time Frame: may be up to six weeks
Incidence of adverse effects (type and severity), incidence of dose limiting toxicities, changes in key laboratory measures
may be up to six weeks
Pharmacokinetics of PHIN-214
Time Frame: up to six weeks
plasma concentration of PHIN-214
up to six weeks
Pharmacokinetics of PHIN-214 metabolite
Time Frame: up to six weeks
plasma concentration of PHIN-214 metabolite
up to six weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunogenicity of PHIN-214
Time Frame: up to six weeks
anti-drug antibody testing
up to six weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood pressure
Time Frame: up to six weeks
Blood pressure (vital signs)
up to six weeks
Heart rate
Time Frame: up to six weeks
Heart rate (vital signs)
up to six weeks
12-lead ECG
Time Frame: up to six weeks
12-lead ECG
up to six weeks
Oxygenation level
Time Frame: up to six weeks
Oxygenation level by pulse oximeter
up to six weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PharmaIN

Investigators

  • Study Chair: Cynthia C Jones, PharmaIN

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 3, 2022

Primary Completion (Estimated)

May 31, 2026

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

July 28, 2022

First Submitted That Met QC Criteria

August 4, 2022

First Posted (Actual)

August 8, 2022

Study Record Updates

Last Update Posted (Estimated)

September 5, 2025

Last Update Submitted That Met QC Criteria

September 3, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PHIN-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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