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

Sponsor
PharmaIN (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05490888
Collaborator
(none)
13
2
1
11.9
6.5
0.5

Study Details

Study Description

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
  • 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 cirrhosis.

Study Design

Study Type:
Interventional
Anticipated 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 Cirrhotic Patients
Actual Study Start Date :
Jan 3, 2022
Anticipated Primary Completion Date :
Oct 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

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 Names:
  • Terlipressin derivative
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of dose limiting toxicities [up to two weeks]

      Incidence of dose limiting toxicities

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

      incidence of stopping criteria

    3. incidence of AEs [up to two weeks]

      incidence of AEs

    Secondary Outcome Measures

    1. PK of PHIN-214 [up to two weeks]

      plasma concentration of PHIN-214

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

      AUC of PHIN-214

    3. PK of PHIN-214 metabolite [up to two weeks]

      plasma concentration of PHIN-214 metabolite

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

      AUC of PHIN-214 metabolite

    Other Outcome Measures

    1. various exploratory markers of efficacy [up to two weeks]

      systolic and diastolic blood pressure

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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) <90 ml/min/1.73 m2 or Cr >1.2 mg/dL.

    5. Hepatic encephalopathy ≥ grade 1.

    6. Patients with Grade ≥ 3 or larger esophageal varices (per Conn's classification of esophageal varices) or red spots on most recent eligibility EGD.

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

    8. Use of treatments for Hepatitis C virus within 6 months of Screening or anticipated use during the trial. Positive HCV antibody serology with detectable HCV ribonucleic acid (RNA).

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

    10. Patients with acute hepatitis B; pPatients with known chronic hepatitis B are eligible if treatment regimen is not changed in the 4 weeks prior to study inclusion

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Liver Health Chandler Arizona United States 85224
    2 Mayo Clinic Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • PharmaIN

    Investigators

    • Study Chair: Cynthia C Jones, BS, PharmaIN

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    PharmaIN
    ClinicalTrials.gov Identifier:
    NCT05490888
    Other Study ID Numbers:
    • PHIN-001
    First Posted:
    Aug 8, 2022
    Last Update Posted:
    Aug 8, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by PharmaIN
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 8, 2022