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

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ClinicalTrials.gov Identifier: NCT05490888
Recruitment Status : Recruiting
First Posted : August 8, 2022
Last Update Posted : September 13, 2022
Sponsor:
Information provided by (Responsible Party):
PharmaIN

Study Description
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Brief Summary:
This single ascending dose (SAD) 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 compensated cirrhosis.

Condition or disease Intervention/treatment Phase
Cirrhosis, Liver Liver Fibrosis Ascites Hepatic Drug: PHIN-214 Subcutaneous injection Phase 1

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 once at various dosing levels to establish the maximum tolerated dose in patients with compensated and decompensated cirrhosis.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Single Dose Escalation Study of PHIN-214 in Compensated and Decompensated Cirrhotic Patients
Actual Study Start Date : January 3, 2022
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : February 28, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: single dose of PHIN-214
single ascending dose of PHIN-214
 Drug: PHIN-214 Subcutaneous injection
Single subcutaneous injection with PHIN-214 terlipressin derivative, single ascending dose
Other Name: Terlipressin derivative


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of dose limiting toxicities [ Time Frame: up to two weeks ]
    Incidence of dose limiting toxicities

  2. incidence of stopping criteria [ Time Frame: up to two weeks ]
    incidence of stopping criteria

  3. incidence of AEs [ Time Frame: up to two weeks ]
    incidence of AEs


Secondary Outcome Measures :
  1. PK of PHIN-214 [ Time Frame: up to two weeks ]
    plasma concentration of PHIN-214

  2. AUC of PHIN-214 [ Time Frame: up to two weeks ]
    AUC of PHIN-214

  3. PK of PHIN-214 metabolite [ Time Frame: up to two weeks ]
    plasma concentration of PHIN-214 metabolite

  4. AUC of PHIN-214 metabolite [ Time Frame: up to two weeks ]
    AUC of PHIN-214 metabolite


Other Outcome Measures:
  1. various exploratory markers of efficacy [ Time Frame: up to two weeks ]
    systolic and diastolic blood pressure


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Patients with liver cirrhosis confirmed by reliable biopsy (within 12 months) or reliable Fibroscan >15 kPa at screening.

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. Hepatic encephalopathy ≥ grade 1.
  6. Recipient of a transjugular intrahepatic portosystemic shunt (TIPS).
  7. Known positive HIV serology confirmed by HIV viral load.
  8. 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05490888


Contacts
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Contact: Cynthia C Jones, BS 206-568-1450 ext *104 cjones@pharmain.com

Locations
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United States, Arizona
Arizona Liver Health Recruiting
Chandler, Arizona, United States, 85224
Contact: Angie Coste, FNP-C    480-470-4000    acoste@azliver.com   
Principal Investigator: Naim Alkhouri, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Douglas Simonetto, MD    507-284-4824    Simonetto.douglas@mayo.edu   
Principal Investigator: Douglas Simonetto, MD         
Sponsors and Collaborators
PharmaIN
Investigators
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Study Chair: Cynthia C Jones, BS PharmaIN
More Information
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Responsible Party: PharmaIN
ClinicalTrials.gov Identifier: NCT05490888    
Other Study ID Numbers: PHIN-001
First Posted: August 8, 2022    Key Record Dates
Last Update Posted: September 13, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PharmaIN:
Terlipressin
Cirrhosis
Vasoconstrictor
Additional relevant MeSH terms:
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Liver Cirrhosis
Fibrosis
Ascites
Pathologic Processes
Liver Diseases
 Digestive System Diseases
Terlipressin
Antihypertensive Agents
Vasoconstrictor Agents