Pasireotide LAR in Severe Polycystic Liver Disease

Brief Title

Pasireotide LAR in Severe Polycystic Liver Disease

Official Title

A Randomized, Placebo Controlled Clinical Trial of SOM230 (Pasireotide LAR) In Severe Polycystic Liver Disease

Brief Summary

      The purpose of this study is to compare SOM230 treatment to placebo. The investigators will
      also assess the efficacy and safety of SOM230 in reducing total liver volume and improving
      quality of life.
    

Detailed Description

      Pasireotide (SOM230) is a novel multi-receptor-targeted analog that has high affinity for
      four of the five SST receptor subtypes (SSTr1, SSTr2, SSTr3 and SSTr5); it has a 40-fold
      higher affinity and 158-fold higher functional activity for the SST5 receptor than
      octreotide. Because of its broad receptor binding profile, pasireotide may be more potent in
      Polycystic Liver Disease (PLD) than octreotide. In this randomized double blind placebo
      controlled trial the investigators will compare SOM230 treatment to placebo for 12 months in
      patients with PLD. The primary endpoints will be assessed at 12 months and patients receiving
      placebo then crossed over to SOM230, permitting all participants to receive SOM230 for the
      subsequent two years. Magnetic resonance imaging (MRI) will be used to assess liver volume -
      the primary endpoint, which will be assessed at baseline, end of years 1 and 3. This study
      will assess the efficacy and safety of SOM230 in reducing total liver volume and improving
      quality of life over 12 months. (The investigators will not be assessing efficacy at 24
      months.) The therapy way be effective in PLD but also may prove to be effective for many more
      patients with Polycystic Kidney Disease (PKD) which will be evaluated using eGFR and kidney
      volume using MRI.

      The investigators plan to add other sub-sites in other locations.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Change in Liver Volume

Secondary Outcome

 Percentage Change in Estimated Glomerular Filtration Rate (eGFR)

Condition

Somatostatin Analogs

Intervention

Pasireotide LAR

Study Arms / Comparison Groups

 Pasireotide LAR (SOM230)
Description:  Active Pasireotide LAR

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

48

Start Date

August 2012

Completion Date

September 2018

Primary Completion Date

September 2018

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female Age ≥ 18 years.

          -  Diagnosis of PLD associated with ADPKD (meeting the Modified Ravine's criteria) or
             isolated ADPLD (defined by the criteria described by Reynolds et al)

          -  Severe PLD defined as a liver volume >4000mL or symptomatic disease due to mass
             effects from hepatic cysts (must be able to undergo MRI or CT scan to determine this).

          -  Not a candidate for or declining surgical intervention.

          -  Capable of providing informed consent.

          -  Life expectancy ≥ 12 weeks

          -  Patients with a known history of impaired fasting blood glucose (glucose >100 and
             <126) may be included at the discretion of the PI. These patients should be monitored
             closely throughout the trial and antihyperglycemic treatment adjusted as necessary.
             Patients that are deemed non eligible due to elevated glucose can be re-screened after
             adequate medical treatment.

          -  Adequate end organ function as defined by:

          -  Adequate bone marrow function:

               -  WBC ≥ 2.5 x 109/L

               -  Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

               -  Platelets ≥ 100 x 109/L

               -  Hb ≥ 9 g/dL

          -  No evidence of significant liver disease:

               -  Serum bilirubin ≤1.5 x ULN

               -  INR < 1.3

               -  ALT and AST ≤ 2 x ULN

          -  Estimated glomerular filtration rate (eGFR) >30 ml/min/m2

          -  Serum amylase and lipase ≤ 1.5 x ULN

          -  Alkaline phosphatase ≤ 2.5 x ULN

          -  Written informed consent obtained prior to any screening procedures

          -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests and other study procedures

        Exclusion Criteria:

          -  Patients will be considered ineligible for this study if they meet any of the
             following criteria:

          -  Patients with a known hypersensitivity to SST analogs or any component of the
             pasireotide LAR or SQ formulations.

          -  Patients with known malabsorption syndrome, short bowel or chologenic diarrhea not
             controlled by specific therapeutic means.

          -  Patients with abnormal coagulation (PT or a PTT elevated by 30% above normal limits).

          -  Patients on continuous anticoagulation therapy. Patients who were on anticoagulant
             therapy must complete a washout period of at least 10 days and have confirmed normal
             coagulation parameters before study inclusion.

          -  Patients with symptomatic cholelithiasis.

          -  Patients who are not biochemically euthyroid.

          -  Patients with known history of hypothyroidism are eligible if they are on adequate and
             stable re-placement thyroid hormone therapy for at least 3 months.

          -  Serum magnesium ≥ ULN

          -  QT-related exclusion criteria:

          -  QTcF at screening > 470 msec

          -  Patients with a history of syncope or family history of idiopathic sudden death

          -  Patients who have sustained or clinically significant cardiac arrhythmias

          -  Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac
             failure, clinically significant/symptomatic bradycardia, or high-grade AV block

          -  Patients with concomitant disease(s) that could prolong QT such as autonomic
             neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled
             hypothyroidism or cardiac failure

          -  Family history of long QT syndrome

          -  Concomitant medications known to prolong the QT interval.

          -  Potassium < or = to 3.5

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study such as:

          -  Patients who have Uncontrolled diabetes as defined by HbA1c>8%* despite adequate
             therapy

          -  Patients with the presence of active or suspected acute or chronic uncontrolled
             infection or with a history of immunodeficiency, including a positive HIV test result
             (ELISA and Western blot). An HIV test will not be required; however, previous medical
             history will be reviewed.

          -  Non-malignant medical illnesses that are uncontrolled or whose control may be
             jeopardized by the treatment with this study treatment.

          -  Liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis
             or chronic persistent hepatitis.

          -  Baseline ALT or AST >3x ULN

          -  Patients with life-threatening autoimmune and ischemic disorders.

          -  Uncontrolled hypertension

          -  Patients who have a history of a primary malignancy, with the exception of locally
             excised non-melanoma skin cancer and carcinoma in situ of uterine cervix. (Patients
             who have had no evidence of disease from primary cancer for 3 or more years are
             allowed to participate in the study.)

          -  History of pancreatitis

          -  Patients with a known history of hepatitis B or C

          -  Presence of Hepatitis B surface antigen (HbsAg)

          -  Presence of Hepatitis C antibody (anti-HCV)

          -  Patients with a history of, or current, alcohol misuse/abuse within the past 12 months

          -  Known gallbladder or bile duct disease, acute or chronic pancreatitis

          -  Patients who have any current or prior medical condition that may interfere with the
             conduct of the study or the evaluation of its results in the opinion of the
             Investigator or the Sponsor's Medical Monitor

          -  Use of an investigational drug within 1 month prior to dosing

          -  Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable or will not be able to complete the entire study
      

Gender

All

Ages

18 Years - 100 Years

Accepts Healthy Volunteers

No

Contacts

Marie C Hogan, MD PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01670110

Organization ID

11-007405


Responsible Party

Principal Investigator

Study Sponsor

Mayo Clinic


Study Sponsor

Marie C Hogan, MD PhD, Principal Investigator, Mayo Clinic


Verification Date

April 2020