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

Cirrhosis, Liver Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05490888
• Other study ID #: PHIN-001
• Status: Recruiting
• Phase: Phase 1
• Start date: January 3, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: PharmaIN
• Contact: Cynthia C Jones, BS
• Phone: 206-568-1450
• Email: cjones[@]pharmain.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 31, 2025
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Body mass index within the range 18 to 40 kg/m2 (inclusive) at screening.

2. Females must be non-pregnant, non-lactating or of non-childbearing potential or using highly efficient contraception for the full duration of the study.

3. Cirrhosis based on histology or a combination of clinical, radiological, or biochemical and classified as Child-Pugh A or B.

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. Estimated glomerular filtration rate (eGFR by CKD-Epi) <60 ml/min/1.73 m2 or Cr >2.0 mg/dL.

5. Uncontrolled hepatic encephalopathy requiring 2 or more medications to manage during the previous 3 months.

6. Recipient of a transjugular intrahepatic portosystemic shunt (TIPS).

7. Known positive HIV serology confirmed by HIV viral load.

8. 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.

Related Conditions & MeSH terms

• Ascites
• Ascites Hepatic
• Cirrhosis, Liver
• Fibrosis
• Liver Cirrhosis
• Liver Fibrosis

Intervention

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

Locations

Country	Name	City	State
United States	Arizona Liver Health	Chandler	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	Texas Liver Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
PharmaIN

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	various exploratory markers of efficacy	systolic and diastolic blood pressure	up to six weeks
Primary	Incidence of dose limiting toxicities	Incidence of dose limiting toxicities	up to sixweeks
Primary	incidence of stopping criteria	incidence of stopping criteria	up to six weeks
Primary	incidence of AEs	incidence of AEs	up to six weeks
Secondary	PK of PHIN-214	plasma concentration of PHIN-214	up to six weeks
Secondary	AUC of PHIN-214	AUC of PHIN-214	up to six weeks
Secondary	PK of PHIN-214 metabolite	plasma concentration of PHIN-214 metabolite	up to six weeks
Secondary	AUC of PHIN-214 metabolite	AUC of PHIN-214 metabolite	up to six weeks