- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02876094
Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy (SMA)
October 13, 2020 updated by: Hugh McMillan
A Pilot, Open-Label, Dose Response Study Investigating the Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy (SMA)
Several factors make the use of celecoxib in human SMA patients appealing including: 1) low-dosing required for potential therapeutic effect (the corresponding dose in humans is much lower than that commonly used in adults and children with; 2) favourable side effect profile of this drug (particularly at the dosing required); 3) the fact that celecoxib crosses the blood brain barrier and 4) demonstration of efficacy in a genetically and pathophysiologically faithful animal mode.
The investigators therefore believe that celecoxib is a promising disease modifying therapy for SMA.
Study Overview
Detailed Description
This is a pilot, open-label, dose-response study in patients with SMA type II or III.
All patients will be treated at each dose of once daily celecoxib (40, 80 and 160 mcg/kg) for a period of two weeks, for a total of 6 weeks (42 days) of treatment.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Ontario
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Ottawa, Ontario, Canada, K1H8L1
- Children's Hospital Of Eastern Ontario
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
8 months to 78 years (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Confirmed genetic diagnosis consistent with SMA that can include: SMN1 gene deletions, rearrangements and/or mutations
- Sufficient clinical information enabling the patient to be classified as either SMA type II or III. (Patients with SMA type II are defined as having achieved the motor milestone of sitting independently for > 30 seconds but not having been able to stand or walk unsupported. Patients with SMA type III are defined as having achieved the motor milestone of standing or walking independently).
- Confirmed genetic test result indicating number of SMN2 gene copies
- Age > 2.0 years old at screening
- Patients weighing at least 12 kg at screening
- Stable dosing (for at least 3 months) of medications that may affect function of muscle, nerve and/or neuromuscular transmission or gene expression (including but not limited to: coenzyme Q10, creatine monohydrate, nutritional supplements, oral salbutamol, valproic acid, sodium phenylbutyrate, hydroxyurea)
- Written informed consent obtained from patient and/or parents or legal guardians
Exclusion Criteria:
- Clinical presentation and/or genetic testing that is not consistent with SMA type II or III
- Inability or unwillingness to swallow celecoxib suspension
- Major surgery (scoliosis repair, G-tube insertion) within past 3 months
- Known hypersensitivity or allergy to celecoxib (including asthma, urticaria and/or other allergic symptoms resulting from prior celecoxib ingestion) or its excipients, or other NSAIDs (non-steroidal anti-inflammatory drugs) including ASA (Acetylsalicylic Acid)
- Known hypersensitivity or allergy to Ora-Blend® or its excipients
- Demonstrated allergic-type reaction to sulfonamides
- Celecoxib use within 2 weeks prior to screening visit
- Known cardiac (ie. uncontrolled heart failure, cerebrovascular bleeding, hypertension requiring the use of anti-hypertensive medication), hepatic (i.e. severe liver impairment or active liver disease), gastrointestinal (i.e. inflammatory bowel disease; active gastric/duodenal/peptic ulcer disease; or active gastrointestinal bleeding), hematologic (ie. thrombocytopenia defined as platelets < 50,000 or hemophilia), respiratory or renal disease(i.e. severe renal impairment defined as creatinine clearance < 30 mL/min) wherein the use of NSAIDs is contraindicated as per Product Monograph dated 03 March 2015.
- Concurrent use of medication contraindicated with Celecoxib use (including but not limited to, warfarin, fluconazole, lithium, hydrochlorothiazide)
- Female who is pregnant or breast feeding
- Female of child-bearing potential who is sexually active and unwilling or unable to use at least one form of highly effective and one effective method of birth control.
- Patients participating in any pharmaceutical clinical trial (with active agent) that could impact with the results of this study
- Inability or refusal to provide informed consent
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Open-label
All patients will be treated at each dose of oral once daily celecoxib (40, 80 and 160 mcg/kg) for a period of two weeks, for a total of 6 weeks (42 days) of treatment.
|
dose-response
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
low-dose oral celecoxib administered to patients with SMA type II and III is associated with an increase in the levels of peripheral leukocyte SMN protein compared to baseline
Time Frame: baseline
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1) Investigate change in peripheral leukocyte SMN protein levels from baseline at each dose (40 mcg/kg, 80 mcg/kg, and 160 mcg/kg) of celecoxib.
|
baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety Profile Measured by Adverse Event Frequency,Type and Severity
Time Frame: 4 weeks post
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1) Determine safety profile as measured by number, type and severity of adverse events reported following administration of low dose celecoxib in patients with type II and III SMA
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4 weeks post
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Recruitment Plan Measured by Number of Potentially Eligible Subjects
Time Frame: 4 weeks post
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Assess understanding of recruitment barriers measured by the number of potentially eligible subjects and response to study recruitment phase.
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4 weeks post
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Compliance Measured by Reported Protocol Deviations
Time Frame: 4 weeks post
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Assess adherence to treatment protocol measured by number of reported protocol deviations.
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4 weeks post
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Eligibility Measured by Number of Screen Failures
Time Frame: 4 weeks post
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Assess appropriateness of eligibility criteria based on number of screen failures.
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4 weeks post
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Delivery Time of Shipped Samples Assessed by Viability
Time Frame: 4 weeks post
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Assess feasibility of shipping laboratory samples to outside centre for analysis.
This will be reported based on the time to deliver and the resulting viability of the received samples by either pre or post testing or both if appropriate.
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4 weeks post
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Hugh McMillan, MD, Children's Hospital of Eastern Ontario Research Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 29, 2019
Primary Completion (Actual)
August 6, 2020
Study Completion (Actual)
August 6, 2020
Study Registration Dates
First Submitted
August 9, 2016
First Submitted That Met QC Criteria
August 18, 2016
First Posted (Estimate)
August 23, 2016
Study Record Updates
Last Update Posted (Actual)
October 19, 2020
Last Update Submitted That Met QC Criteria
October 13, 2020
Last Verified
October 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Neuromuscular Manifestations
- Pathological Conditions, Anatomical
- Spinal Cord Diseases
- Motor Neuron Disease
- Muscular Atrophy
- Atrophy
- Muscular Atrophy, Spinal
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Cyclooxygenase 2 Inhibitors
- Celecoxib
Other Study ID Numbers
- 15/22E
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
Results will be submitted for presentation at an international meeting and subsequently submitted for publication in a major international peer-reviewed medical journal.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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