LPL DeficiencyPhase 2NCT02904772
Alipogene Tiparvovec for the Treatment of LPLD Patients
A Phase 2 study testing alipogene tiparvovec, Prednisolone and Cyclosporins in people with LPL Deficiency, run by UniQure Biopharma B.V. at 2 sites in 2 countries.
Trial summary
The aim of the study is to provide further confirmatory evidence of clinical benefit in LPLD patients treated with alipogene tiparvovec by assessing both the "clinical response" (as defined by a range of parameters), and "the metabolic response" (postprandial CM metabolism) in LPLD patients with and without an… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- LPL Deficiency
- What is being tested?
- alipogene tiparvovec, Prednisolone and Cyclosporins
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Oct 2016to Sep 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
Main inclusion criteria are:
- Patients with a history of severe or multiple pancreatitis attacks despite dietary fat restriction.
- Genetically confirmed diagnosis of LPLD
- Post-heparin plasma LPL protein mass > 5% of normal
- LPL activity ≤20% of normal (in post- heparin plasma)
- Fasting plasma TG concentration >10 mmol/L.
Main exclusion criteria are:
- Females with a positive pregnancy test or who are breastfeeding, or on contraceptive use.
- Patients with a positive HIV, Hepatitis B, Hepatitis C or being positive for tuberculosis.
- Patients under treatment with antiplatelet or other anti-coagulants.
- Patient allergic to or having a condition that prohibits the use of immunosuppressants.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Perelman School of Medicine at The University of Pennsylvania Translational Medicine & Human Genetics
Philadelphia, Pennsylvania, PA19104
Canada1 site
Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, J1H 5N4
About this study
Official title: An Open Label, Multi-centre Trial of Alipogene Tiparvovec for the Treatment of LPLD Patients
The aim of the study is to provide further confirmatory evidence of clinical benefit in LPLD patients treated with alipogene tiparvovec by assessing both the "clinical response" (as defined by a range of parameters), and "the metabolic response" (postprandial CM metabolism) in LPLD patients with and without an immunosuppressant regimen.
Read the detailed description
This is a prospective, interventional, randomised, open-label, parallel group study evaluating the clinical response as well as the dynamics of postprandial chylomicron metabolism in patients treated with alipogene tiparvovec with and without immunosuppressants. The study will be conducted in 12 LPLD patients who will be randomised into the Immuno+ (cyclosporin and mycophenolate mofetil) or the Immuno- group.
- Conditions
- LPL Deficiency
- Being tested
- alipogene tiparvovec, Prednisolone, Cyclosporins, Mycophenolate mofetil
- Medical subject headings
- Hyperlipoproteinemia Type I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alipogene tiparvovecDrug
Also called Glybera
A dose of 1x10(*12) gc/kg alipogene tiparvovec (Glybera) of body weight administered as a single set of intramuscular injections at multiple sites in multiple muscles of both upper legs and if necessary, the lower legs.
PrednisoloneDrug
IV bolus methylprednisolone 1mg/kg half hour prior to administration
CyclosporinsDrug
Immuno + group will receive cyclosporine (3 mg/kg/day) from three days prior to until 12 weeks following IMP administration
Immuno + group will receive Mycophenolate mofetil (2x 1 g/day) from three days prior to until 12 weeks following IMP administration
| Study group | Role | What they receive |
|---|---|---|
| alipogene tiparvovec with IS | Other | Patients in the Immuno+ group will receive an immunosuppressant regimen to be initiated three days prior to alipogene tiparvovec administration. The regimen is to be continued for 12 weeks: Cyclosporins (3 mg/kg/day) and mycophenolate mofetil (2 x 1 g/day). Patients will receive IV bolus of 1mg/kg of methyl Prednisolone half an hour prior to IMP administration. Receives: Drug: alipogene tiparvovec; Drug: Prednisolone; Drug: Cyclosporins; Drug: Mycophenolate mofetil |
| alipogene tiparvovec without IS | Other | Patients in the Immuno- group will not receive an immunosuppressant regimen during 12 weeks. Patients will receive IV bolus of 1mg/kg of methyl Prednisolone half an hour prior to IMP administration. Receives: Drug: alipogene tiparvovec; Drug: Prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Clinical Response of alipogene tiparvovec in LPLD patients
The overall clinical response of alipogene tiparvovec in LPLD patients will be assessed compared to baseline, by a combination of measurements, of which each gives relevant information to obtain enough and solid evidence in a small trial. Each of these outcome measures will be evaluated in combination with the results of other measures (to get an overall conclusion relating the clinical response). Descriptive methods will be used (so no formal statistical analyses will be performed), due to the specific nature and the small sample size of a rare disease trial.
Measured: 2 years
The long term effect of alipogene tiparvovec on post prandial metabolism of chylomicrons (ppCM) in LPLD patients.
CM [3H]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline.
Measured: 2 years
Secondary outcomes (3)
The effect of alipogene tiparvovec on postprandial metabolism of chylomicrons (ppCM) in LPLD patients with and without immunosuppression treatment, at 14 weeks post-administration.
CM [3H]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline.
Measured: Baseline, 14 weeks
Immuno response of alipogene tiparvovec by analysis of antibody formation
The immuno response of alipogene tiparvovec will be assessed by measuring the antibody formation compared to baseline.
Measured: Baseline, 1 and 2 years post dose
Immuno response of alipogene tiparvovec by analysis of T-cell response
T-cell responses against alipogene tiparvovec will be assessed by measuring the T-cell response compared to baseline.
Measured: Baseline, 1 and 2 years post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2016 (estimated)
- Study startOct 2016
- Primary completionJun 2020 (estimated)
- Study completionSep 2020 (estimated)
Why it stopped: uniQure, has decided not to renew the Marketing Authorization of Glybera in the EU. This decision is not related to any safety, efficacy or quality issue
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LPL DeficiencyStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- UniQure Biopharma B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Chiesi Farmaceutici S.p.A.
- Responsible party
- Sponsor
- Investigators
- André Carpentier, MD, Principal investigator, Centre de recherche du Centre hospitalier universitaire de Sherbrooke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02904772
- Sponsor's protocol ID
- Gly-CD-001
- Status last verified
- Jul 2017
- First submitted
- 10 May 2016
- Last updated
- 17 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Multi-centre Trial of Alipogene Tiparvovec for the Treatment of LPLD Patients
- ClinicalTrials.gov ID
- NCT02904772
- Acronym / sponsor ID
- Gly-CD-001
- Conditions
- LPL Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: uniQure, has decided not to renew the Marketing Authorization of Glybera in the EU. This decision is not related to any safety, efficacy or quality issue
- Enrolment
- 0 participants (actual)
- Lead sponsor
- UniQure Biopharma B.V.Industry (pharma, biotech, devices)
- Collaborators
- Chiesi Farmaceutici S.p.A.
- Study start
- Oct 2016
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Sep 2020 (estimated)
- First posted
- 19 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to provide further confirmatory evidence of clinical benefit in LPLD patients treated with alipogene tiparvovec by assessing both the "clinical response" (as defined by a range of parameters), and "the metabolic response" (postprandial CM metabolism) in LPLD patients with and without an immunosuppressant regimen.
Detailed description
This is a prospective, interventional, randomised, open-label, parallel group study evaluating the clinical response as well as the dynamics of postprandial chylomicron metabolism in patients treated with alipogene tiparvovec with and without immunosuppressants. The study will be conducted in 12 LPLD patients who will be randomised into the Immuno+ (cyclosporin and mycophenolate mofetil) or the Immuno- group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| alipogene tiparvovec with IS | Other | Drug: alipogene tiparvovec, Drug: Prednisolone, Drug: Cyclosporins, Drug: Mycophenolate mofetilPatients in the Immuno+ group will receive an immunosuppressant regimen to be initiated three days prior to alipogene tiparvovec administration. The regimen is to be continued for 12 weeks: Cyclosporins (3 mg/kg/day) and mycophenolate mofetil (2 x 1 g/day). Patients will receive IV bolus of 1mg/kg of methyl Prednisolone half an hour prior to IMP administration. |
| alipogene tiparvovec without IS | Other | Drug: alipogene tiparvovec, Drug: PrednisolonePatients in the Immuno- group will not receive an immunosuppressant regimen during 12 weeks. Patients will receive IV bolus of 1mg/kg of methyl Prednisolone half an hour prior to IMP administration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| alipogene tiparvovecAlso: GlyberaA dose of 1x10(*12) gc/kg alipogene tiparvovec (Glybera) of body weight administered as a single set of intramuscular injections at multiple sites in multiple muscles of both upper legs and if necessary, the lower legs. | Drug | alipogene tiparvovec with IS, alipogene tiparvovec without IS |
| PrednisoloneIV bolus methylprednisolone 1mg/kg half hour prior to administration | Drug | alipogene tiparvovec with IS, alipogene tiparvovec without IS |
| CyclosporinsImmuno + group will receive cyclosporine (3 mg/kg/day) from three days prior to until 12 weeks following IMP administration | Drug | alipogene tiparvovec with IS |
| Mycophenolate mofetilImmuno + group will receive Mycophenolate mofetil (2x 1 g/day) from three days prior to until 12 weeks following IMP administration | Drug | alipogene tiparvovec with IS |
Primary outcome
The Clinical Response of alipogene tiparvovec in LPLD patients
Time frame: 2 years
The overall clinical response of alipogene tiparvovec in LPLD patients will be assessed compared to baseline, by a combination of measurements, of which each gives relevant information to obtain enough and solid evidence in a small trial. Each of these outcome measures will be evaluated in combination with the results of other measures (to get an overall conclusion relating the clinical response). Descriptive methods will be used (so no formal statistical analyses will be performed), due to the specific nature and the small sample size of a rare disease trial.
The long term effect of alipogene tiparvovec on post prandial metabolism of chylomicrons (ppCM) in LPLD patients.
Time frame: 2 years
CM [3H]-activity will be assessed during ppCM testing pre- and post-dose, compared to baseline.
3 secondary outcomes
The effect of alipogene tiparvovec on postprandial metabolism of chylomicrons (ppCM) in LPLD patients with and without immunosuppression treatment, at 14 weeks post-administration.
Time frame: Baseline, 14 weeks
Immuno response of alipogene tiparvovec by analysis of antibody formation
Time frame: Baseline, 1 and 2 years post dose
Immuno response of alipogene tiparvovec by analysis of T-cell response
Time frame: Baseline, 1 and 2 years post dose
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2017.
- Individual participant dataSharing planned: No
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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.
André Carpentier, MD principal investigator
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing alipogene tiparvovec, Prednisolone and Cyclosporins in people with LPL Deficiency, run by UniQure Biopharma B.V. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: withdrawn, as of the sponsor's last update on 17 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Canada. 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. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
The Clinical Response of alipogene tiparvovec in LPLD patients (time frame: 2 years). 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?
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 17 Aug 2017.