StrokePhase 4ONTIME PilotNCT02321436
Study to Assess Impact of Dysport Injections Early After Stroke on Upper Limb Spasticity Progression
A Phase 4 study testing Botulinum toxin type A in people with Stroke and Upper Limb Spasticity, run by Ipsen at 4 sites in 4 countries.
Trial summary
The purpose of this study is to investigate if early administration (i.e. within 12 weeks after stroke) of Dysport® 500 U injections may delay the appearance or the progression of upper limb symptomatic spasticity. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Stroke, Upper Limb Spasticity
- What is being tested?
- Botulinum toxin type A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Dec 2014to Mar 2016
- Phase
- Phase 4
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 2 to 12 weeks after first ever stroke according to the World Health Organisation criteria (previous transient ischaemic attack or clinically silent infarct on computerised tomography (CT)/magnetic resonance imaging (MRI) are not counted as previous stroke)
- Stroke confirmed by CT/MRI scan and classified as ischaemic/haemorrhagic stroke
- Presence of spasticity:
- either symptomatic, based on symptomatic spasticity criteria (i.e. at least one of the following items: impacted passive/active function, involuntary movements, or pain ≥4 on a numeric pain rating scale [NPRS]), in addition to increased muscle tone [Modified Ashworth Scale, MAS ≥2])
- or only increased muscle tone (MAS≥2)
Who cannot join
- Neuromuscular junction (NMJ) diseases, or any other neurological disorders (including prior local joint, tendon, and intrinsic muscle disorders) that could potentially interfere with assessment of spasticity in the primary targeted muscle group selected by the Investigator and in agreement with the subject
- Currently receiving drugs affecting NMJ transmission e.g. aminoglycosides, aminoquinolines, cyclosporine, D penicillamine
- Previous surgery of the affected muscles/ ligaments/tendons
- Severe comorbidities (e.g. congestive heart failure, myocardial infarction, multiple organ failure, hepatic renal failures, severe infections)
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
Malaysia1 site
Neurology Laboratory -University Malaya Medical Centre
Kuala Lumpur, 59100
Philippines1 site
Center for Neurodiagnostic and Therapeutic Services Metropolitan Medical Center
Manila, 1003
Singapore1 site
TTSH Rehabilitation Centre Ang Mo Kio Community Hospital
Singapore, 569766
Thailand1 site
Department of rehabilitation Medicine Faculty of medicine Siriraj Hospital, Madihol University Hospital
Bangkok, 10700
About this study
Official title: Asian Multicentre, Double Blind, Randomised, Placebo Controlled Pilot Study, to Assess the Impact of Dysport® Intramuscular Injections When Administered Within the First 12 Weeks After Stroke on the Time to Spasticity Progression in Adult Subjects With Upper Limb (UL) Spasticity.
The purpose of this study is to investigate if early administration (i.e. within 12 weeks after stroke) of Dysport® 500 U injections may delay the appearance or the progression of upper limb symptomatic spasticity.
- Conditions
- Stroke, Upper Limb Spasticity
- Being tested
- Botulinum toxin type A, Placebo
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum toxin type ABiological
Also called AbobotulinumtoxinA (Dysport®)
Subjects to receive Dysport® 500U administered intramuscularly in the targeted upper limb.
PlaceboDrug
Placebo administered intramuscularly in the targeted upper limb.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Active comparator | Dysport® 500U intramuscular injection Receives: Biological: Botulinum toxin type A |
| Placebo Group | Placebo comparator | Placebo intramuscular injection Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time Between the Initial Injection and the Appearance of Reinjection Criteria as Evaluated by the Modified Ashworth Scale (MAS) and Spasticity Symptoms
The appearance of increased muscle tone was assessed using the MAS (scale ranges from 0 [no increase in muscle tone] to 4 [affected part rigid in flexion or extension]). For confirmation of reinjection criteria appearance, a subject had to have a MAS score in the primary targeted muscle group of ≥2 and at least 1 of the following 4 criteria confirming signs of symptomatic spasticity in the UL:
- A Numeric Pain Rating Scale (NPRS) pain score ≥ 4 (NPRS ranges from 0 [no pain] to 10 [severe pain])
- An impact on passive function measured by a score of ≥ 1 on the 4-point Likert scale (scale ranges from 0 [no impact] to 3 [severe impact])
- An impact on active function measured by a score of ≥ 1 on the 4-point Likert scale
- An involuntary movements score ≥1 on the 4-point Likert scale in relevant upper limb.
Results are reported overall for subjects with both symptomatic and asymptomatic spasticity.
Measured: From Week 4 up to Week 28
Secondary outcomes (5)
Mean Change in MAS of the Primary Targeted Muscle Group.
Increased muscle tone in the primary muscle group (selected by the investigator at the first visit, based on his/her clinical judgement and in agreement with the subject, in one of the following muscle groups: elbow flexors or pronators, wrist flexors, or finger flexors) was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). Least Squares (LS) mean change from baseline to each subsequent visit (including the subject's last study visit) of the MAS score is reported.
Measured: From baseline up to Week 28
Mean Change in Fugl-Meyer Assessment for Evaluation of UL Motor Impairment.
The Fugl-Meyer assessment is a validated tool for measuring motor functioning, balance, sensation, and joint functioning in the upper or lower limbs of subjects with post-stroke hemiplegia. The assessment scale is comprised of 155 items across 5 domains: motor functioning, sensory functioning, balance, joint range of motion and joint pain. For this study, only the UL motor part was assessed using the following criteria:
- Upper Extremity (from 0 to 36) B. Wrist (from 0 to 10) C. Hand (from 0 to 14) D. Coordination / Speed (from 0 to 6)
Total motor function scores (A-D [from 0 to 66]) were calculated and LS mean changes from baseline up to (but not including) the visit when the reinjection criteria were met were reported.
Higher values for change from baseline indicated a better outcome.
Measured: From baseline up to Week 28
Global Assessment of Changes at Last Visit
Global assessment of changes was assessed by the investigator from Week 4 up to (but not including) the visit when the reinjection criteria were met. This endpoint was assessed by the investigator using a 5-point Likert scale to answer the following question: How does your patient feel compared to his/her condition at the first visit?
- Much better
- Better
- No change
- Worse
- Much worse
Results are reported overall for subjects with both symptomatic and asymptomatic spasticity.
Measured: From Week 4 up to Week 28
Number of Concomitant Non-drug Therapy Sessions.
The number of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). All concomitant therapies in the indication of "Post Stroke UL Spasticity" were counted by subject from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date.
Measured: From baseline up to Week 28
Mean Duration of Concomitant Non-drug Therapy Sessions.
The duration of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). Overall duration of concomitant therapies in the indication of "Post Stroke UL Spasticity" was computed for the period from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date.
Measured: From baseline up to Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2014 (estimated)
- Study startDec 2014
- Primary completionMar 2016
- Study completionMar 2016
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 StrokeStudies of the same condition, open and under way.
- More trials run by IpsenThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ipsen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02321436
- Sponsor's protocol ID
- Y-79-52120-197
- Acronym
- ONTIME Pilot
- Status last verified
- Sep 2022
- First submitted
- 17 Dec 2014
- Last updated
- 28 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
Publications
Rosales RL, Balcaitiene J, Berard H, Maisonobe P, Goh KJ, Kumthornthip W, Mazlan M, Latif LA, Delos Santos MMD, Chotiyarnwong C, Tanvijit P, Nuez O, Kong KH. Early AbobotulinumtoxinA (Dysport(R)) in Post-Stroke Adult Upper Limb Spasticity: ONTIME Pilot Study. Toxins (Basel). 2018 Jun 21;10(7):253. doi: 10.3390/toxins10070253.
PubMed 29933562
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Asian Multicentre, Double Blind, Randomised, Placebo Controlled Pilot Study, to Assess the Impact of Dysport® Intramuscular Injections When Administered Within the First 12 Weeks After Stroke on the Time to Spasticity Progression in Adult Subjects With Upper Limb (UL) Spasticity.
- ClinicalTrials.gov ID
- NCT02321436
- Acronym / sponsor ID
- ONTIME Pilot / Y-79-52120-197
- Conditions
- Stroke, Upper Limb Spasticity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- IpsenIndustry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 22 Dec 2014 (estimated)
- Results
- Posted 26 Jun 2017
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 investigate if early administration (i.e. within 12 weeks after stroke) of Dysport® 500 U injections may delay the appearance or the progression of upper limb symptomatic spasticity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Active comparator | Biological: Botulinum toxin type ADysport® 500U intramuscular injection |
| Placebo Group | Placebo comparator | Drug: PlaceboPlacebo intramuscular injection |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 2 to 12 weeks after first ever stroke according to the World Health Organisation criteria (previous transient ischaemic attack or clinically silent infarct on computerised tomography (CT)/magnetic resonance imaging (MRI) are not counted as previous stroke)
- Stroke confirmed by CT/MRI scan and classified as ischaemic/haemorrhagic stroke
- Presence of spasticity:
Key exclusion criteria (4 listed)
- Neuromuscular junction (NMJ) diseases, or any other neurological disorders (including prior local joint, tendon, and intrinsic muscle disorders) that could potentially interfere with assessment of spasticity in the primary targeted muscle group selected by the Investigator and in agreement with the subject
- Currently receiving drugs affecting NMJ transmission e.g. aminoglycosides, aminoquinolines, cyclosporine, D penicillamine
- Previous surgery of the affected muscles/ ligaments/tendons
- Severe comorbidities (e.g. congestive heart failure, myocardial infarction, multiple organ failure, hepatic renal failures, severe infections)
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 |
|---|---|---|
| Botulinum toxin type AAlso: AbobotulinumtoxinA (Dysport®)Subjects to receive Dysport® 500U administered intramuscularly in the targeted upper limb. | Biological | Treatment group |
| PlaceboPlacebo administered intramuscularly in the targeted upper limb. | Drug | Placebo Group |
Primary outcome
Time Between the Initial Injection and the Appearance of Reinjection Criteria as Evaluated by the Modified Ashworth Scale (MAS) and Spasticity Symptoms
Time frame: From Week 4 up to Week 28
The appearance of increased muscle tone was assessed using the MAS (scale ranges from 0 [no increase in muscle tone] to 4 [affected part rigid in flexion or extension]). For confirmation of reinjection criteria appearance, a subject had to have a MAS score in the primary targeted muscle group of ≥2 and at least 1 of the following 4 criteria confirming signs of symptomatic spasticity in the UL: 1. A Numeric Pain Rating Scale (NPRS) pain score ≥ 4 (NPRS ranges from 0 [no pain] to 10 [severe pain]) 2. An impact on passive function measured by a score of ≥ 1 on the 4-point Likert scale (scale ranges from 0 [no impact] to 3 [severe impact]) 3. An impact on active function measured by a score of ≥ 1 on the 4-point Likert scale 4. An involuntary movements score ≥1 on the 4-point Likert scale in relevant upper limb. Results are reported overall for subjects with both symptomatic and asymptomatic spasticity.
5 secondary outcomes
Mean Change in MAS of the Primary Targeted Muscle Group.
Time frame: From baseline up to Week 28
Mean Change in Fugl-Meyer Assessment for Evaluation of UL Motor Impairment.
Time frame: From baseline up to Week 28
Global Assessment of Changes at Last Visit
Time frame: From Week 4 up to Week 28
Number of Concomitant Non-drug Therapy Sessions.
Time frame: From baseline up to Week 28
Mean Duration of Concomitant Non-drug Therapy Sessions.
Time frame: From baseline up to Week 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29933562Rosales RL, Balcaitiene J, Berard H, Maisonobe P, Goh KJ, Kumthornthip W, Mazlan M, Latif LA, Delos Santos MMD, Chotiyarnwong C, Tanvijit P, Nuez O, Kong KH. Early AbobotulinumtoxinA (Dysport(R)) in Post-Stroke Adult Upper Limb Spasticity: ONTIME Pilot Study. Toxins (Basel). 2018 Jun 21;10(7):253. doi: 10.3390/toxins10070253.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
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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.
Ipsen Medical Director study director
Ipsen
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Botulinum toxin type A in people with Stroke and Upper Limb Spasticity, run by Ipsen at 4 sites in 4 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 5 inclusion and 4 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 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Malaysia, Philippines, Singapore, Thailand. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 26 Jun 2017). 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?
Time Between the Initial Injection and the Appearance of Reinjection Criteria as Evaluated by the Modified Ashworth Scale (MAS) and Spasticity Symptoms (time frame: From Week 4 up to Week 28). 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 NCT02321436, 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 28 Sep 2022.