Peripheral Vascular DiseasesPhase 3TAMARISNCT00566657
Efficacy and Safety of XRP0038/NV1FGF in Critical Limb Ischemia Patients With Skin Lesions
A Phase 3 study testing riferminogene pecaplasmid in people with Peripheral Vascular Diseases, run by Sanofi at 32 sites in 32 countries.
Trial summary
Primary objective is to demonstrate the superiority of riferminogene pecaplasmid (XRP0038/NV1FGF) over placebo in the prevention of major amputation above the ankle of the treated leg or of death from any cause, whichever comes first, in critical limb ischemia (CLI) patients with skin lesions. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Peripheral Vascular Diseases
- What is being tested?
- riferminogene pecaplasmid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 525 participants
- Where
- 32 sitesin 32 countries
- Study dates
- Nov 2007to Aug 2012
- Phase
- Phase 3
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Having peripheral artery disease at the stage of Critical Limb Ischemia (CLI) with skin lesions (either ulcer(s) or gangrene);
- With objective evidence of CLI such as ankle systolic pressure <70 mmHg and/or toe systolic pressure <50 mmHg or transcutaneous oxygen pressure (TcPO2) <30 mmHg;
- Unsuitable for standard revascularization of his/her peripheral arterial disease;
- Having a negative screening for cancer.
Who cannot join
- Previous major amputation on the leg to be treated or planned major amputation within the first month following randomization;
- Known Buerger's disease;
- Successful lower extremity revascularization procedure within 3 months prior randomization;
- Uncontrolled blood pressure defined as systolic blood pressure (SBP) ≥180 mmHg or diastolic blood pressure (DBP) ≥110 mmHg despite adequate antihypertensive treatment;
- Acute cardiovascular events within 3 months prior to randomization;
- Active proliferative retinopathy and severe macular oedema;
Show all 10Show fewer
- Previous or current history of malignant disease within the past 5 years;
- Previous treatment with systemic angiogenic factors or with stem cells therapy;
- Pregnant or breast-feeding woman or woman of childbearing potential not protected by an effective contraceptive method of birth control. Man not following effective contraceptive method with his partner of childbearing potential during the course of the study.
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Trial locations and contacts
32 sites in 32 countries.
32 sites in 32 countries
United States1 site
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey
Australia1 site
Sanofi-Aventis Administrative Office
Macquarie Park, New South Wales
United Kingdom1 site
Sanofi-Aventis Administrative Office
Guildford, Surrey
About this study
Official title: A Randomized Double-Blind Placebo-Controlled Parallel Group Study of the Efficacy and Safety of XRP0038/NV1FGF on Amputation or Any Death in Critical Limb Ischemia Patients With Skin Lesions
Primary objective is to demonstrate the superiority of riferminogene pecaplasmid (XRP0038/NV1FGF) over placebo in the prevention of major amputation above the ankle of the treated leg or of death from any cause, whichever comes first, in critical limb ischemia (CLI) patients with skin lesions.
Secondary objectives are to evaluate:
- The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to major amputation;
- The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to death;
- The safety of riferminogene pecaplasmid in the study population.
Read the detailed description
The study consists in 6-week treatment then a follow-up period up to 12 months. A follow-up contact is then scheduled 6 months later.
Per protocol amendment a 18-month long-term safety survey was added.
- Conditions
- Peripheral Vascular Diseases
- Being tested
- riferminogene pecaplasmid, Placebo (for riferminogene pecaplasmid)
- Keywords
- Critical Limb Ischemia, Peripheral Artery Disease, Plasmid based gene therapy
- Medical subject headings
- Peripheral Vascular Diseases, Chronic Limb-Threatening Ischemia, Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
riferminogene pecaplasmidBiological
Also called NV1FGF, XRP0038
Formulation: 5 ml glass vials containing 2,5 ml riferminogene pecaplasmid
Route: intramuscular (IM) injection of 2.5 mL in the ischemic leg to be treated
Placebo (for riferminogene pecaplasmid)Biological
Formulation: 5 ml glass vials containing 2,5 ml placebo
Route: IM injection of 2.5 mL in the ischemic leg to be treated
| Study group | Role | What they receive |
|---|---|---|
| Riferminogene pecaplasmid | Experimental | 4 administrations of riferminogene pecaplasmid 4 mg at 2-week intervals Receives: Biological: riferminogene pecaplasmid |
| Placebo | Placebo comparator | 4 administrations of placebo (for riferminogene pecaplasmid) at 2-week intervals Receives: Biological: Placebo (for riferminogene pecaplasmid) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to major amputation of the treated leg or death from any cause, whichever comes first
Measured: From randomization up to 12 months
Secondary outcomes (3)
Time to first major amputation of the treated leg
Measured: From randomization up to 12 months
Time to death from any cause
Measured: From randomization up to 12 months
Number of participants with adverse events as a measure of safety
Measured: From 1st treatment administration up to death, or the earliest of Day 360 or last contact/assessment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2007 (estimated)
- Study startNov 2007
- Primary completionAug 2010
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Peripheral Vascular DiseasesStudies of the same condition, open and under way.
- More trials run by SanofiThe 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
- 525 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ICD CSD, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00566657
- Sponsor's protocol ID
- EFC6145
- Other IDs
- 2006-006277-24
- Acronym
- TAMARIS
- Status last verified
- Mar 2016
- First submitted
- 30 Nov 2007
- Last updated
- 2 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Van Belle E, Nikol S, Norgren L, Baumgartner I, Driver V, Hiatt WR, Belch J. Insights on the role of diabetes and geographic variation in patients with critical limb ischaemia. Eur J Vasc Endovasc Surg. 2011 Sep;42(3):365-73. doi: 10.1016/j.ejvs.2011.04.030. Epub 2011 Jun 21.
PubMed 21696982Belch J, Hiatt WR, Baumgartner I, Driver IV, Nikol S, Norgren L, Van Belle E; TAMARIS Committees and Investigators. Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limb ischaemia. Lancet. 2011 Jun 4;377(9781):1929-37. doi: 10.1016/S0140-6736(11)60394-2. Epub 2011 May 28.
PubMed 21621834
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blind Placebo-Controlled Parallel Group Study of the Efficacy and Safety of XRP0038/NV1FGF on Amputation or Any Death in Critical Limb Ischemia Patients With Skin Lesions
- ClinicalTrials.gov ID
- NCT00566657
- Acronym / sponsor ID
- TAMARIS / EFC6145
- Conditions
- Peripheral Vascular Diseases
- Keywords
- Critical Limb Ischemia, Peripheral Artery Disease, Plasmid based gene therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 525 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Nov 2007
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 3 Dec 2007 (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.
Primary objective is to demonstrate the superiority of riferminogene pecaplasmid (XRP0038/NV1FGF) over placebo in the prevention of major amputation above the ankle of the treated leg or of death from any cause, whichever comes first, in critical limb ischemia (CLI) patients with skin lesions.
Secondary objectives are to evaluate:
- The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to major amputation;
- The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to death;
- The safety of riferminogene pecaplasmid in the study population.
Detailed description
The study consists in 6-week treatment then a follow-up period up to 12 months. A follow-up contact is then scheduled 6 months later.
Per protocol amendment a 18-month long-term safety survey was added.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Riferminogene pecaplasmid | Experimental | Biological: riferminogene pecaplasmid4 administrations of riferminogene pecaplasmid 4 mg at 2-week intervals |
| Placebo | Placebo comparator | Biological: Placebo (for riferminogene pecaplasmid)4 administrations of placebo (for riferminogene pecaplasmid) at 2-week intervals |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Having peripheral artery disease at the stage of Critical Limb Ischemia (CLI) with skin lesions (either ulcer(s) or gangrene);
- With objective evidence of CLI such as ankle systolic pressure <70 mmHg and/or toe systolic pressure <50 mmHg or transcutaneous oxygen pressure (TcPO2) <30 mmHg;
- Unsuitable for standard revascularization of his/her peripheral arterial disease;
- Having a negative screening for cancer.
Key exclusion criteria (10 listed)
- Previous major amputation on the leg to be treated or planned major amputation within the first month following randomization;
- Known Buerger's disease;
- Successful lower extremity revascularization procedure within 3 months prior randomization;
- Uncontrolled blood pressure defined as systolic blood pressure (SBP) ≥180 mmHg or diastolic blood pressure (DBP) ≥110 mmHg despite adequate antihypertensive treatment;
- Acute cardiovascular events within 3 months prior to randomization;
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 |
|---|---|---|
| riferminogene pecaplasmidAlso: NV1FGF, XRP0038Formulation: 5 ml glass vials containing 2,5 ml riferminogene pecaplasmid Route: intramuscular (IM) injection of 2.5 mL in the ischemic leg to be treated | Biological | Riferminogene pecaplasmid |
| Placebo (for riferminogene pecaplasmid)Formulation: 5 ml glass vials containing 2,5 ml placebo Route: IM injection of 2.5 mL in the ischemic leg to be treated | Biological | Placebo |
Primary outcome
Time to major amputation of the treated leg or death from any cause, whichever comes first
Time frame: From randomization up to 12 months
3 secondary outcomes
Time to first major amputation of the treated leg
Time frame: From randomization up to 12 months
Time to death from any cause
Time frame: From randomization up to 12 months
Number of participants with adverse events as a measure of safety
Time frame: From 1st treatment administration up to death, or the earliest of Day 360 or last contact/assessment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2016.
- Results publication: PubMed 21696982Van Belle E, Nikol S, Norgren L, Baumgartner I, Driver V, Hiatt WR, Belch J. Insights on the role of diabetes and geographic variation in patients with critical limb ischaemia. Eur J Vasc Endovasc Surg. 2011 Sep;42(3):365-73. doi: 10.1016/j.ejvs.2011.04.030. Epub 2011 Jun 21.
- Results publication: PubMed 21621834Belch J, Hiatt WR, Baumgartner I, Driver IV, Nikol S, Norgren L, Van Belle E; TAMARIS Committees and Investigators. Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limb ischaemia. Lancet. 2011 Jun 4;377(9781):1929-37. doi: 10.1016/S0140-6736(11)60394-2. Epub 2011 May 28.
Related trials for Peripheral Vascular Diseases
Active, not recruiting
Improving Visual Field Deficits With Noninvasive Brain Stimulation
Visual Field Defect, Peripheral, Stroke
Active, not recruiting
SUCCESS (SelUtion, Safety, effiCaCy, hEalth economicS and promS) PTA Study
Peripheral Artery Disease
Active, not recruiting
Wearable Insoles for Recurrent Diabetic Ulcer Prevention
Diabetes, Peripheral Neuropathy
RecruitingPhase 3
Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease
Peripheral Artery Disease (PAD)
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
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.
ICD CSD study director
Sanofi
32 sites in 32 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing riferminogene pecaplasmid in people with Peripheral Vascular Diseases, run by Sanofi at 32 sites in 32 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 4 inclusion and 10 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 2 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Argentina, Australia, Austria, Belarus and 27 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Time to major amputation of the treated leg or death from any cause, whichever comes first (time frame: From randomization up to 12 months). 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 NCT00566657, which also lists 2 linked publications.
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 2 May 2016.