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

Primary Purpose

Cirrhosis, Liver, Liver Fibrosis, Ascites Hepatic

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

PHIN-214 Subcutaneous injection

About this trial

This is an interventional treatment trial for Cirrhosis, Liver focused on measuring Terlipressin, Cirrhosis, Vasoconstrictor, Refractory Ascites

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Body mass index within the range 18 to 40 kg/m2 (inclusive) at screening.
Females must be non-pregnant, non-lactating or of non-childbearing potential or using highly efficient contraception for the full duration of the study.
Patients with liver cirrhosis confirmed by reliable biopsy (within 12 months) or reliable Fibroscan >15 kPa at screening.

Exclusion Criteria:

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.
History of diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, or any other disorder associated with fluid or sodium imbalance.
Significant kidney disease
Estimated glomerular filtration rate (eGFR by CKD-Epi) <60 ml/min/1.73 m2 or Cr >2.0 mg/dL.
Hepatic encephalopathy ≥ grade 1.
Recipient of a transjugular intrahepatic portosystemic shunt (TIPS).
Known positive HIV serology confirmed by HIV viral load.
Patients with acute hepatitis B; patients with known chronic hepatitis B are eligible if treatment regimen is not changed in the 4 weeks prior to study inclusion

Sites / Locations

Arizona Liver HealthRecruiting
Mayo ClinicRecruiting
Texas Liver InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

single dose of PHIN-214

multiple daily dosing of PHIN-214

Arm Description

single ascending dose of PHIN-214

multiple doses of PHIN-214, daily for 28 days

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities

incidence of stopping criteria

incidence of AEs

Secondary Outcome Measures

PK of PHIN-214

plasma concentration of PHIN-214

AUC of PHIN-214

PK of PHIN-214 metabolite

plasma concentration of PHIN-214 metabolite

AUC of PHIN-214 metabolite

Full Information

NCT ID

NCT05490888

First Posted

July 28, 2022

Last Updated

July 6, 2023

Sponsor

PharmaIN

1. Study Identification

Unique Protocol Identification Number

NCT05490888

Brief Title

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

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 3, 2022 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

February 28, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PharmaIN

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This single and multiple ascending dose (SAD and MAD) study evaluates PHIN-214, being studied to determine the safety, tolerability, and pharmacokinetics, and establish the maximum tolerated dose of this compound in patients with Child Pugh A and B Cirrhosis.

Detailed Description

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 Europe for the treatment of bleeding esophageal varices and HRS type 1 and is usually administered as an IV bolus. 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. As a partial V1a agonist that traffics into the bloodstream from a subcutaneous depot, this derivative is designed to be gentler than terlipressin and has been well tolerated at the injection site, to date. This study will evaluate the use of PHIN-214 administered at various dosing levels to establish the maximum tolerated dose in patients with Child Pugh A and B Cirrhosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cirrhosis, Liver, Liver Fibrosis, Ascites Hepatic

Keywords

Terlipressin, Cirrhosis, Vasoconstrictor, Refractory Ascites

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

37 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

single dose of PHIN-214

Arm Type

Experimental

Arm Description

single ascending dose of PHIN-214

Arm Title

multiple daily dosing of PHIN-214

Arm Type

Experimental

Arm Description

multiple doses of PHIN-214, daily for 28 days

Intervention Type

Drug

Intervention Name(s)

PHIN-214 Subcutaneous injection

Other Intervention Name(s)

Terlipressin derivative

Intervention Description

Single or multiple subcutaneous injection(s) with PHIN-214 terlipressin derivative, single ascending dose or multiple ascending dose

Primary Outcome Measure Information:

Title

Incidence of dose limiting toxicities

Description

Incidence of dose limiting toxicities

Time Frame

up to sixweeks

Title

incidence of stopping criteria

Description

incidence of stopping criteria

Time Frame

up to six weeks

Title

incidence of AEs

Description

incidence of AEs

Time Frame

up to six weeks

Secondary Outcome Measure Information:

Title

PK of PHIN-214

Description

plasma concentration of PHIN-214

Time Frame

up to six weeks

Title

AUC of PHIN-214

Description

AUC of PHIN-214

Time Frame

up to six weeks

Title

PK of PHIN-214 metabolite

Description

plasma concentration of PHIN-214 metabolite

Time Frame

up to six weeks

Title

AUC of PHIN-214 metabolite

Description

AUC of PHIN-214 metabolite

Time Frame

up to six weeks

Other Pre-specified Outcome Measures:

Title

various exploratory markers of efficacy

Description

systolic and diastolic blood pressure

Time Frame

up to six weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Body mass index within the range 18 to 40 kg/m2 (inclusive) at screening. Females must be non-pregnant, non-lactating or of non-childbearing potential or using highly efficient contraception for the full duration of the study. Cirrhosis based on histology or a combination of clinical, radiological, or biochemical and classified as Child-Pugh A or B. Exclusion Criteria: 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. History of diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, or any other disorder associated with fluid or sodium imbalance. Significant kidney disease Estimated glomerular filtration rate (eGFR by CKD-Epi) <60 ml/min/1.73 m2 or Cr >2.0 mg/dL. Hepatic encephalopathy > grade 2 in the previous 3 months. Stable drug treatment for HE is not exclusionary. Recipient of a transjugular intrahepatic portosystemic shunt (TIPS). Known positive HIV serology confirmed by HIV viral load. Subjects with acute infections, including acute viral hepatitis are to be excluded. Subjects with chronic hepatitis B are eligible if treatment regimen is stable ≥ 3 months prior to study inclusion.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Cynthia C Jones, BS

Phone

206-568-1450

Ext

*104

cjones@pharmain.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cynthia C Jones, BS

Organizational Affiliation

PharmaIN

Official's Role

Study Chair

Facility Information:

Facility Name

Arizona Liver Health

City

Chandler

State/Province

Arizona

ZIP/Postal Code

85224

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Angie Coste, FNP-C

Phone

480-470-4000

acoste@azliver.com

First Name & Middle Initial & Last Name & Degree

Naim Alkhouri, MD

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Douglas Simonetto, MD

Phone

507-284-4824

Simonetto.douglas@mayo.edu

First Name & Middle Initial & Last Name & Degree

Douglas Simonetto, MD

Facility Name

Texas Liver Institute

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78215

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Eric Lawitz, MD

Phone

210-253-3426

Lawitz@txliver.com

First Name & Middle Initial & Last Name & Degree

Eric Lawitz, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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