Spinal Muscular Atrophy Type IIPhase 2NCT01302600
Safety and Efficacy of Olesoxime (TRO19622) in 3-25 Years SMA Patients.
A Phase 2 study testing Olesoxime in people with Spinal Muscular Atrophy Type II and Spinal Muscular Atrophy Type III Non Ambulant, run by Hoffmann-La Roche at 22 sites in 7 countries.
Trial summary
Assess the efficacy and the safety of olesoxime in SMA type 2 or type 3 non ambulant patients aged 3-25 years Read more about this study
- Who is it for?
- Ages 3 to 25 years
- Conditions the study is for
- Spinal Muscular Atrophy Type II, Spinal Muscular Atrophy Type III Non Ambulant
- What is being tested?
- Olesoxime
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 165 participants
- Where
- 22 sitesin 7 countries
- Study dates
- Nov 2010to Oct 2013
- 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 3 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Weakness and hypotonia consistent with a clinical diagnosis of spinal muscular atrophy (SMA) type II or III
- Laboratory documentation of homozygous absence of SMNI exon 7 and/or deletion and mutation on other allele
- MFM relative score (percentage of the maximum sum of both dimensions) >= 15% (D1 + D2 score)
- HFMS score at baseline >= 3
- Non ambulant patients defined as patients with HFMS score =< 38
- Must be 3 years of age or older, but younger than 26 years of age, at time of enrolment
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- Age of onset of symptoms =< 3 years of age
- Signed informed consent of patient and/or parents/guardian
- Laboratory results drawn within 31 days prior to start of study entry demonstrating no clinically significant abnormalities
- Ability to take the study treatment (tested at screening after informed consent)
Who cannot join
- Evidence of renal dysfunction, blood dysplasia, hepatic insufficiency, symptomatic pancreatitis, congenital heart defect, known history of metabolic acidosis, hypertension,significant central nervous system impairment, or neurodegenerative or neuromuscular disease other than SMA
- Any clinically significant ECG abnormality
- Any acute co-morbid condition interfering with the well-being of the subject within 7 days of enrolment including bacterial infection, viral infectious processes, food poisoning, temperature > 37.0 °C, the need for acute treatment or observation due to any other reason, as judged by the investigator; patient can be included after resolution of the acute event
- Use of medications intended for the treatment of SMA including riluzole, valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine, growth hormone, anabolic steroids, probenecid, oral or parenteral use of corticosteroids at entry, agents anticipated to increase or decrease muscle strength or agents with known or presumed histone deacetylase (HDAC) inhibition, within 30 days prior to study entry. Subjects who use a nebulizer or require an inhaler to steroids will be allowed in the study; however oral use of steroids is prohibited. The oral use of salbutamol is permitted with the following restrictions: patients should have been on salbutamol for at least 6 months before inclusion in the trial, with good tolerance. The dose of salbutamol should remain constant for the duration of the trial. The use of inhaled beta-agonists (for the treatment of asthma crisis for example) is allowed.
- Spinal rod or fixation for scoliosis within the past 6 months or anticipated need of rod or fixation within 6 months of enrolment.
- Inability to meet study visit requirements or cooperate reliably with functional testing
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- Coexisting medical conditions that contraindicate travel, testing or study medications
- Olesoxime is contraindicated in subjects/patients who develop drug hypersensitivity to it or one of the formulation excipients including hypersensitivity to sesame oil.
- Patients with hemostasis disorders
- Patients with known biliary tract obstruction
- Current or planned pregnancy or nursing period
- For Women: Failure to use one of the following safe methods of contraception:
- Female condoms, diaphragm or coil, each used in combination with spermicides
- Intra-uterine device
- Hormonal contraception in combination with a mechanical method of contraception
- Participation in any other investigational drug or therapy study within the previous 3 months.
Trial locations and contacts
22 sites in 7 countries.
22 sites in 7 countries
France6 sites
Hôpital Femme-Mère-Enfant
Bron, 69677
Hôpital Raymond Poincaré
Garches, 92380
CHRU Hôpital R. Salengro
Lille, 59037
Hôpital La Timone
Marseille, 13385
CHU de Montpellier, Hôpital Gui de Chauliac
Montpellier, 34295
Groupe hospitalier Armand-Trousseau
Paris, 75012
Italy6 sites
Istituto Giannina Gaslini
Genova, 16147
AOU Policlinico
Messina, 98 125
Centro Dino Ferrari, Milano
Milan, 20122
NEuroMuscular Omnicentre (NEMO)
Milan, 20162
Bambino Gesu' Research Children's Hospital
Roma, 165
Policlinico Universitario "Agostino Gemelli",
Roma, 168
Germany3 sites
University of Essen
Essen, 45122
Universitat Klinikum Freiburg
Freiburg im Breisgau, 79106
Friedrich-Baur-Institute
München, 80336
United Kingdom3 sites
Birmingham Heartlands Hospital
Birmingham, B92 0AN
Dubowitz Neuromuscular Centre
London, WC1N 1EH
Institute of Human Genetics
Newcastle, NE1 3BZ
Belgium2 sites
University Hospitals
Ghent, 9000
University Hospitals
Leuven, 3000
About this study
Official title: Phase II, Multicenter, Randomized, Adaptive, Double-blind, Placebo Controlled Study to Assess Safety and Efficacy of Olesoxime (TRO19622) in 3-25 Year Old Spinal Muscular Atrophy (SMA) Patients.
Assess the efficacy and the safety of olesoxime in SMA type 2 or type 3 non ambulant patients aged 3-25 years
Read the detailed description
This study is a multicenter, double-blind, randomized, adaptive, parallel groups, placebo controlled 3-stage study in patients with SMA type 2 or non ambulant type 3.
Stage 1 DMC 3-month safety assessment: An independent Data Monitoring Committee (DMC)will assess the safety of olesoxime every 3 months.
Stage 2 Efficacy/futility analyses at one year: A first interim efficacy analysis will be performed after all patients have been treated for one year (52 weeks) in order to assess the need to continue the study to reach the planned objective. In the event of positive and significant results in favor of olesoxime, the study will be considered as successful and all patients will be switched to olesoxime to allow the assessment of the sustainability of the treatment effect and safety. If the results are significantly in favor of placebo, the study will be discontinued for failure (futility).
Stage 3 Efficacy and safety analysis at two years: The expected study duration is of 2 years (104 weeks) to show efficacy. If the study is not discontinued for futility or medication regimen is changed due to success, the study will therefore continue until planned completion i.e. 104 weeks.
- Being tested
- Olesoxime, Placebo
- Medical subject headings
- Spinal Muscular Atrophies of Childhood
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlesoximeDrug
Liquid suspension formulation, 100 mg/ml at a dose of 10 mg/kg will be administered once a day with food at dinner
PlaceboDrug
0.1ml/kg once a day with food at dinner.
| Study group | Role | What they receive |
|---|---|---|
| Olesoxime | Experimental | 100 patients in this arm. liquid suspension Receives: Drug: Olesoxime |
| Placebo | Placebo comparator | 50 patients enrolled in this arm. liquid suspension Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Motor Function Measure
Motor function Measure (MFM) D1+D2 score
Measured: every 6 months
Secondary outcomes (1)
responder analyses on MFM and HFMS, time to 4 point decrease on HFMS, CMAP/MUNE, PedsQL, FVC, CGI and safety
Measured: every 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2011 (estimated)
- Study startNov 2010
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular Atrophy Type IIStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Association Française contre les Myopathies (AFM), Paris
- Responsible party
- Sponsor
- Investigators
- Enrico Bertini, MD, Principal investigator, Bambino Gesu Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01302600
- Sponsor's protocol ID
- WN29836
- Other IDs
- TRO19622 CL E Q 1275-1
- Status last verified
- Nov 2016
- First submitted
- 18 Feb 2011
- Last updated
- 22 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bertini E, Dessaud E, Mercuri E, Muntoni F, Kirschner J, Reid C, Lusakowska A, Comi GP, Cuisset JM, Abitbol JL, Scherrer B, Ducray PS, Buchbjerg J, Vianna E, van der Pol WL, Vuillerot C, Blaettler T, Fontoura P; Olesoxime SMA Phase 2 Study Investigators. Safety and efficacy of olesoxime in patients with type 2 or non-ambulatory type 3 spinal muscular atrophy: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jul;16(7):513-522. doi: 10.1016/S1474-4422(17)30085-6. Epub 2017 Apr 28.
PubMed 28460889
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Multicenter, Randomized, Adaptive, Double-blind, Placebo Controlled Study to Assess Safety and Efficacy of Olesoxime (TRO19622) in 3-25 Year Old Spinal Muscular Atrophy (SMA) Patients.
- ClinicalTrials.gov ID
- NCT01302600
- Acronym / sponsor ID
- WN29836
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Collaborators
- Association Française contre les Myopathies (AFM), Paris
- Study start
- Nov 2010
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 24 Feb 2011 (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.
Assess the efficacy and the safety of olesoxime in SMA type 2 or type 3 non ambulant patients aged 3-25 years
Detailed description
This study is a multicenter, double-blind, randomized, adaptive, parallel groups, placebo controlled 3-stage study in patients with SMA type 2 or non ambulant type 3.
Stage 1 DMC 3-month safety assessment: An independent Data Monitoring Committee (DMC)will assess the safety of olesoxime every 3 months.
Stage 2 Efficacy/futility analyses at one year: A first interim efficacy analysis will be performed after all patients have been treated for one year (52 weeks) in order to assess the need to continue the study to reach the planned objective. In the event of positive and significant results in favor of olesoxime, the study will be considered as successful and all patients will be switched to olesoxime to allow the assessment of the sustainability of the treatment effect and safety. If the results are significantly in favor of placebo, the study will be discontinued for failure (futility).
Stage 3 Efficacy and safety analysis at two years: The expected study duration is of 2 years (104 weeks) to show efficacy. If the study is not discontinued for futility or medication regimen is changed due to success, the study will therefore continue until planned completion i.e. 104 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Olesoxime | Experimental | Drug: Olesoxime100 patients in this arm. liquid suspension |
| Placebo | Placebo comparator | Drug: Placebo50 patients enrolled in this arm. liquid suspension |
Who may qualify
- Ages
- 3 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Weakness and hypotonia consistent with a clinical diagnosis of spinal muscular atrophy (SMA) type II or III
- Laboratory documentation of homozygous absence of SMNI exon 7 and/or deletion and mutation on other allele
- MFM relative score (percentage of the maximum sum of both dimensions) >= 15% (D1 + D2 score)
- HFMS score at baseline >= 3
- Non ambulant patients defined as patients with HFMS score =< 38
Key exclusion criteria (16 listed)
- Evidence of renal dysfunction, blood dysplasia, hepatic insufficiency, symptomatic pancreatitis, congenital heart defect, known history of metabolic acidosis, hypertension,significant central nervous system impairment, or neurodegenerative or neuromuscular disease other than SMA
- Any clinically significant ECG abnormality
- Any acute co-morbid condition interfering with the well-being of the subject within 7 days of enrolment including bacterial infection, viral infectious processes, food poisoning, temperature > 37.0 °C, the need for acute treatment or observation due to any other reason, as judged by the investigator; patient can be included after resolution of the acute event
- Use of medications intended for the treatment of SMA including riluzole, valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine, growth hormone, anabolic steroids, probenecid, oral or parenteral use of corticosteroids at entry, agents anticipated to increase or decrease muscle strength or agents with known or presumed histone deacetylase (HDAC) inhibition, within 30 days prior to study entry. Subjects who use a nebulizer or require an inhaler to steroids will be allowed in the study; however oral use of steroids is prohibited. The oral use of salbutamol is permitted with the following restrictions: patients should have been on salbutamol for at least 6 months before inclusion in the trial, with good tolerance. The dose of salbutamol should remain constant for the duration of the trial. The use of inhaled beta-agonists (for the treatment of asthma crisis for example) is allowed.
- Spinal rod or fixation for scoliosis within the past 6 months or anticipated need of rod or fixation within 6 months of enrolment.
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 |
|---|---|---|
| OlesoximeLiquid suspension formulation, 100 mg/ml at a dose of 10 mg/kg will be administered once a day with food at dinner | Drug | Olesoxime |
| Placebo0.1ml/kg once a day with food at dinner. | Drug | Placebo |
Primary outcome
Motor Function Measure
Time frame: every 6 months
Motor function Measure (MFM) D1+D2 score
1 secondary outcome
responder analyses on MFM and HFMS, time to 4 point decrease on HFMS, CMAP/MUNE, PedsQL, FVC, CGI and safety
Time frame: every 3 months
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 22 Nov 2016.
- Derived from this study: PubMed 28460889Bertini E, Dessaud E, Mercuri E, Muntoni F, Kirschner J, Reid C, Lusakowska A, Comi GP, Cuisset JM, Abitbol JL, Scherrer B, Ducray PS, Buchbjerg J, Vianna E, van der Pol WL, Vuillerot C, Blaettler T, Fontoura P; Olesoxime SMA Phase 2 Study Investigators. Safety and efficacy of olesoxime in patients with type 2 or non-ambulatory type 3 spinal muscular atrophy: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jul;16(7):513-522. doi: 10.1016/S1474-4422(17)30085-6. Epub 2017 Apr 28.
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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.
Enrico Bertini, MD principal investigator
Bambino Gesu Hospital
22 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Olesoxime in people with Spinal Muscular Atrophy Type II and Spinal Muscular Atrophy Type III Non Ambulant, run by Hoffmann-La Roche at 22 sites in 7 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 10 inclusion and 16 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 22 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in France, Italy, Germany, United Kingdom, Belgium and 2 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 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 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?
Motor Function Measure (time frame: every 6 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 NCT01302600, 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 22 Nov 2016.