Somatostatin AnalogsPhase 2SOM230NCT01670110
Pasireotide LAR in Severe Polycystic Liver Disease
A Phase 2 study testing Pasireotide LAR in people with Somatostatin Analogs and Polycystic Liver Disease, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Somatostatin Analogs, Polycystic Liver Disease, Autosomal Dominant Polycystic Kidney Disease
- What is being tested?
- Pasireotide LAR
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to Sep 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Placebo Controlled Clinical Trial of SOM230 (Pasireotide LAR) In Severe Polycystic Liver Disease
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.
Read the 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.
- Conditions
- Somatostatin Analogs, Polycystic Liver Disease, Autosomal Dominant Polycystic Kidney Disease, Autosomal Dominant Polycystic Liver Disease
- Being tested
- Pasireotide LAR, Placebo
- Keywords
- Polycystic Liver Disease, Autosomal dominant polycystic kidney disease, Autosomal dominant polycystic liver disease, Somatostatin analogs, Pasireotide LAR, SOM230
- Medical subject headings
- Polycystic liver disease, Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pasireotide LARDrug
Injectible, 60mg per month
PlaceboDrug
To be injected once per month
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide LAR (SOM230) | Active comparator | Active Pasireotide LAR Receives: Drug: Pasireotide LAR |
| placebo injection | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Liver Volume
Percent change was calculated for liver volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month
Measured: baseline , 12 month
Change in Kidney Volume
Percent change was calculated for kidney volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month
Measured: baseline to 12 months
Secondary outcomes (6)
Percentage Change in Estimated Glomerular Filtration Rate (eGFR)
eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. This value at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Measured: Baseline, 12 months
Percentage Change in Serum Creatinine
Serum creatinine level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Measured: Baseline, 12 months
Percent Change in Blood Glucose
Blood glucose (mg/dLb) level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Measured: Baseline, 12 months
Percentage Change in Hemoglobin A1C
Hemoglobin A1C level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Measured: Baseline, 12 months
Percentage Change in Heart Rate
Heart rate, measured in beats per minute (BPM), at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Measured: Baseline, 12 months
Change in Quality of Life
Measured using the SF-36 health survey, which consist of eight subscales each scored on a range of 0 to 100 (0=worst imaginable, 100=best imaginable). Change calculated from baseline = 12 month value-baseline value
Measured: Baseline, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2012 (estimated)
- Study startAug 2012
- Primary completionSep 2018
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Somatostatin AnalogsStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marie Hogan, Mayo Clinic
- Investigators
- Marie C Hogan, MD PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01670110
- Sponsor's protocol ID
- 11-007405
- Acronym
- SOM230
- Status last verified
- Apr 2020
- First submitted
- 17 Aug 2012
- Last updated
- 1 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hogan MC, Chamberlin JA, Vaughan LE, Waits AL, Banks C, Leistikow K, Oftsie T, Madsen C, Edwards M, Glockner J, Kremers WK, Harris PC, LaRusso NF, Torres VE, Masyuk TV. Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement: A Randomized Clinical Trial. Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1267-1278. doi: 10.2215/CJN.13661119. Epub 2020 Aug 25.
PubMed 32843370
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo Controlled Clinical Trial of SOM230 (Pasireotide LAR) In Severe Polycystic Liver Disease
- ClinicalTrials.gov ID
- NCT01670110
- Acronym / sponsor ID
- SOM230 / 11-007405
- Conditions
- Somatostatin Analogs, Polycystic Liver Disease, Autosomal Dominant Polycystic Kidney Disease, Autosomal Dominant Polycystic Liver Disease
- Keywords
- Polycystic Liver Disease, Autosomal dominant polycystic kidney disease, Autosomal dominant polycystic liver disease, Somatostatin analogs, Pasireotide LAR, SOM230
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Aug 2012 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 21 Aug 2012 (estimated)
- Results
- Posted 2 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pasireotide LAR (SOM230) | Active comparator | Drug: Pasireotide LARActive Pasireotide LAR |
| placebo injection | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
Key exclusion criteria (36 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pasireotide LARInjectible, 60mg per month | Drug | Pasireotide LAR (SOM230) |
| PlaceboTo be injected once per month | Drug | placebo injection |
Primary outcome
Change in Liver Volume
Time frame: baseline , 12 month
Percent change was calculated for liver volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month
Change in Kidney Volume
Time frame: baseline to 12 months
Percent change was calculated for kidney volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month
6 secondary outcomes
Percentage Change in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline, 12 months
Percentage Change in Serum Creatinine
Time frame: Baseline, 12 months
Percent Change in Blood Glucose
Time frame: Baseline, 12 months
Percentage Change in Hemoglobin A1C
Time frame: Baseline, 12 months
Percentage Change in Heart Rate
Time frame: Baseline, 12 months
Change in Quality of Life
Time frame: Baseline, 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32843370Hogan MC, Chamberlin JA, Vaughan LE, Waits AL, Banks C, Leistikow K, Oftsie T, Madsen C, Edwards M, Glockner J, Kremers WK, Harris PC, LaRusso NF, Torres VE, Masyuk TV. Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement: A Randomized Clinical Trial. Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1267-1278. doi: 10.2215/CJN.13661119. Epub 2020 Aug 25.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie C Hogan, MD PhD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pasireotide LAR in people with Somatostatin Analogs and Polycystic Liver Disease, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Liver Volume (time frame: baseline , 12 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01670110, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2020.