Familial Chylomicronemia Syndrome (FCS)Phase 3NCT01514461
A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome
A Phase 3 study testing LCQ908 in people with Familial Chylomicronemia Syndrome (FCS), run by Novartis Pharmaceuticals at 14 sites in 8 countries.
Trial summary
The purpose of this study is to determine whether LCQ908 is effective and safe in lowering triglycerides in subjects with Familial Chylomicronemia Syndrome (FCS) (Hyperlipoproteinemia [HLP] type I). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Chylomicronemia Syndrome (FCS)
- What is being tested?
- LCQ908
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 14 sitesin 8 countries
- Study dates
- Jul 2012to May 2014
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent given before any assessment was performed for Period I.
- Male and female patients ages at least 18 years of age.
- Fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) at Screening.
- An established diagnosis of FCS (HLP Type I) confirmed through ultracentrifugation or by documented medical history of a fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) and by documentation of any of the following at Screening or during the Screening Period:
- Confirmed homozygote or compound heterozygote for known loss-of-function mutations in Type I-causing genes (such as LPL, apo C II, GPIHBP1, or LMF1)
- Post heparin plasma LPL activity of ≤ 20% of normal
- Confirmed presence of LPL inactivating antibodies
- History of pancreatitis.
Who cannot join
- Current pancreatitis, pancreatitis was required to be inactive for at least 1 week prior to the screening Visit.
- Treatment with fish oil preparations within 4 weeks prior to randomization.
- Treatment with bile acid binding resins (i.e., colesevelam, etc.) within 4 weeks prior to randomization.
- Treatment with fibrates within 4 weeks prior to randomization.
- Glybera [alipogene tiparvovec (AAV1-LPLS447X)] gene therapy exposure within the two years prior to screening.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
Show all 14Show fewer
- Any surgical or medical conditions, acute or unstable chronic disease which may, based on the investigator's opinion, jeopardize the patient in case of participation in the study or might significantly alter the absorption, distribution, metabolism or excretion of the study drug.
- History of drug or alcohol abuse within the 12 months prior to randomization or evidence of such abuse at screening.
- Evidence of liver disease or liver injury as indicated by abnormal liver function tests such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), or serum bilirubin.
- Estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2 or history of chronic renal disease.
- Participation in any clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations, or any other limitation of participation based on local regulations.
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive HCG laboratory test.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 100 days after discontinuation of investigational study drug.
Trial locations and contacts
14 sites in 8 countries.
14 sites in 8 countries
Canada3 sites
Novartis Investigative Site
Chicoutimi, Quebec, G7H 7P2
Novartis Investigative Site
Ouest-Montreal, H2W1R7
Novartis Investigative Site
Ste-Foy, Quebec, G1V4M6
France3 sites
Novartis Investigative Site
Bron, 69677
Novartis Investigative Site
Nantes, 44093
Novartis Investigative Site
Paris, 75651
Germany2 sites
Novartis Investigative Site
Cologne, 50937
Novartis Investigative Site
Hamburg, 20246
Spain2 sites
Novartis Investigative Site
Málaga, Andalusia, 29010
Novartis Investigative Site
Seville, Andalusia, 41013
United States1 site
Novartis Investigative Site
Seatlle, Washington, 98104
About this study
The purpose of this study is to determine whether LCQ908 is effective and safe in lowering triglycerides in subjects with Familial Chylomicronemia Syndrome (FCS) (Hyperlipoproteinemia [HLP] type I). Data from this study will be used to support a registration submission of LCQ908 20 mg and 40 mg as treatment of chylomicronemia in subjects with FCS (HLP Type 1).
- Conditions
- Familial Chylomicronemia Syndrome (FCS)
- Being tested
- LCQ908, Placebo
- Keywords
- Hyperlipoproteinemia (HLP Type I), Fasting Triglycerides
- Medical subject headings
- Familial hyperchylomicronemia syndrome, Hyperlipoproteinemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LCQ908Drug
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
PlaceboDrug
Also called LCQ908
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
| Study group | Role | What they receive |
|---|---|---|
| LCQ908 20 mg | Experimental | In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed.
In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily.
A low fat diet will be followed and recorded in patient diary. Receives: Drug: LCQ908; Drug: Placebo |
| LCQ908 40 mg | Experimental | In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed.
In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily.
A low fat diet will be followed and recorded in patient diary. Receives: Drug: LCQ908; Drug: Placebo |
| Placebo | Placebo comparator | In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily.
In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily.
A low fat diet will be followed and recorded in patient diary. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Fasting Triglycerides From Baseline to 12 Weeks
Blood samples were collected for a fasting lipid panel, including triglycerides. If the 12-week value was missing, the measurement value at 12 weeks or the last available post-baseline measurement value during the double-blind treatment period was analyzed. Baseline is defined as the average of fasting triglyceride values taken at day -3 and day 1. Adjusted geometric means are calculated by back-transforming the adjusted means from the model and expressing as a percentage change from baseline.
Measured: Baseline to 12 weeks
Secondary outcomes (11)
Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline or Final Fasting TG < 8.4 mmol/L (750 mg/dL)
Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.
Measured: Baseline, 12 weeks, 24 weeks, 52 weeks
Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL)
Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.
Measured: 12 weeks, 24 weeks, 52 weeks
Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline
Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.
Measured: Baseline, 12 weeks, 24 weeks, 52 weeks
Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds
Percentage of patients reaching target values of <1000 mg/dL or target values of < 2000 mg/dL for fasting triglycerides is reported. Pecentage calculated as (m/n)*100; where 'm' The number of patients who reach target values for fasting triglyceride, 'n' the number of patients with non-missing fasting triglyceride.
Measured: 12 weeks, 24 weeks, 52 weeks
Percent Change From Baseline in Fasting Triglycerides
Measured: Baseline, 24 weeks, 52 weeks
Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12
Post prandial peak triglycerides - maximum triglyceride value over 0-24 hours Post prandial triglycerides AUC0-24 - area under the time curve for triglycerides over 0-24 Adjusted geometric means are calculated by back-transforming the adjusted means from the model and expressed as a percentage change from baseline. hours
Measured: 0-24 hours at Baseline, Week 12
Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax)
Lowest observed blood concentration (Cmin) and observed maximum blood concentration (Cmax) following drug administration derived from non-compartmental analysis using scheduled sampling time for the whole dataset.
Measured: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Pharmacokinetics of LCQ908- Area Under the Plasma Concentration Time Curve AUC (0-24hour)
The area under the concentration-time curve from time zero to 24 hours after drug administration was calculated by using linear trapezoidal rule.
Measured: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Pharmacokinetics of LCQ908- Time to Reach Maximum Concentration Following Drug Administration Tmax (Hours)
Measured: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Pharmacokinetics of LCQ908- Average Observed Blood Concentration (Cavg)
Average observed blood concentration measured by (AUC0-24)/24.
Measured: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2012 (estimated)
- Study startJul 2012
- Primary completionMay 2014
- Study completionMay 2014
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.
- Other trials for Familial Chylomicronemia Syndrome (FCS)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01514461
- Sponsor's protocol ID
- CLCQ908B2302
- Other IDs
- 2011-005535-68
- Status last verified
- May 2015
- First submitted
- 21 Dec 2011
- Last updated
- 3 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome
- ClinicalTrials.gov ID
- NCT01514461
- Acronym / sponsor ID
- CLCQ908B2302
- Conditions
- Familial Chylomicronemia Syndrome (FCS)
- Keywords
- Hyperlipoproteinemia (HLP Type I), Fasting Triglycerides
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 23 Jan 2012 (estimated)
- Results
- Posted 3 Jun 2015
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 determine whether LCQ908 is effective and safe in lowering triglycerides in subjects with Familial Chylomicronemia Syndrome (FCS) (Hyperlipoproteinemia [HLP] type I). Data from this study will be used to support a registration submission of LCQ908 20 mg and 40 mg as treatment of chylomicronemia in subjects with FCS (HLP Type 1).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| LCQ908 20 mg | Experimental | Drug: LCQ908, Drug: PlaceboIn period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet will be followed and recorded in patient diary. |
| LCQ908 40 mg | Experimental | Drug: LCQ908, Drug: PlaceboIn period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet will be followed and recorded in patient diary. |
| Placebo | Placebo comparator | Drug: PlaceboIn period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily. In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily. A low fat diet will be followed and recorded in patient diary. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent given before any assessment was performed for Period I.
- Male and female patients ages at least 18 years of age.
- Fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) at Screening.
- An established diagnosis of FCS (HLP Type I) confirmed through ultracentrifugation or by documented medical history of a fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) and by documentation of any of the following at Screening or during the Screening Period:
- History of pancreatitis.
Key exclusion criteria (14 listed)
- Current pancreatitis, pancreatitis was required to be inactive for at least 1 week prior to the screening Visit.
- Treatment with fish oil preparations within 4 weeks prior to randomization.
- Treatment with bile acid binding resins (i.e., colesevelam, etc.) within 4 weeks prior to randomization.
- Treatment with fibrates within 4 weeks prior to randomization.
- Glybera [alipogene tiparvovec (AAV1-LPLS447X)] gene therapy exposure within the two years prior to screening.
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 |
|---|---|---|
| LCQ908LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg | Drug | LCQ908 20 mg, LCQ908 40 mg |
| PlaceboAlso: LCQ908LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg | Drug | LCQ908 20 mg, LCQ908 40 mg, Placebo |
Primary outcome
Percent Change in Fasting Triglycerides From Baseline to 12 Weeks
Time frame: Baseline to 12 weeks
Blood samples were collected for a fasting lipid panel, including triglycerides. If the 12-week value was missing, the measurement value at 12 weeks or the last available post-baseline measurement value during the double-blind treatment period was analyzed. Baseline is defined as the average of fasting triglyceride values taken at day -3 and day 1. Adjusted geometric means are calculated by back-transforming the adjusted means from the model and expressing as a percentage change from baseline.
11 secondary outcomes
Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline or Final Fasting TG < 8.4 mmol/L (750 mg/dL)
Time frame: Baseline, 12 weeks, 24 weeks, 52 weeks
Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL)
Time frame: 12 weeks, 24 weeks, 52 weeks
Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline
Time frame: Baseline, 12 weeks, 24 weeks, 52 weeks
Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds
Time frame: 12 weeks, 24 weeks, 52 weeks
Percent Change From Baseline in Fasting Triglycerides
Time frame: Baseline, 24 weeks, 52 weeks
Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12
Time frame: 0-24 hours at Baseline, Week 12
Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax)
Time frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Pharmacokinetics of LCQ908- Area Under the Plasma Concentration Time Curve AUC (0-24hour)
Time frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Pharmacokinetics of LCQ908- Time to Reach Maximum Concentration Following Drug Administration Tmax (Hours)
Time frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Pharmacokinetics of LCQ908- Average Observed Blood Concentration (Cavg)
Time frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12
Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death
Time frame: 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
14 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LCQ908 in people with Familial Chylomicronemia Syndrome (FCS), run by Novartis Pharmaceuticals at 14 sites in 8 countries.
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 8 inclusion and 14 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 3 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Canada, France, Germany, Spain, United States and 3 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 3 Jun 2015). 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?
Percent Change in Fasting Triglycerides From Baseline to 12 Weeks (time frame: Baseline to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jun 2015.