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Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy (SMA)

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ClinicalTrials.gov Identifier: NCT02876094
Recruitment Status : Not yet recruiting
First Posted : August 23, 2016
Last Update Posted : July 27, 2018
Sponsor:
Collaborators:
Families of Spinal Muscular Atrophy
Gwendolyn Strong Foundation
Information provided by (Responsible Party):
Hugh McMillan, Children's Hospital of Eastern Ontario

August 9, 2016
August 23, 2016
July 27, 2018
September 3, 2018
July 2019   (Final data collection date for primary outcome measure)
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 ]
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.
Same as current
Complete list of historical versions of study NCT02876094 on ClinicalTrials.gov Archive Site
  • Safety Profile Measured by Adverse Event Frequency,Type and Severity [ Time Frame: 4 weeks post ]
    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
  • Recruitment Plan Measured by Number of Potentially Eligible Subjects [ Time Frame: 4 weeks post ]
    Assess understanding of recruitment barriers measured by the number of potentially eligible subjects and response to study recruitment phase.
  • Compliance Measured by Reported Protocol Deviations [ Time Frame: 4 weeks post ]
    Assess adherence to treatment protocol measured by number of reported protocol deviations.
  • Eligibility Measured by Number of Screen Failures [ Time Frame: 4 weeks post ]
    Assess appropriateness of eligibility criteria based on number of screen failures.
  • Delivery Time of Shipped Samples Assessed by Viability [ Time Frame: 4 weeks post ]
    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.
Same as current
Not Provided
Not Provided
 
Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy
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.
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.
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Spinal Muscular Atrophy (SMA)
Drug: celecoxib
dose-response
Other Name: CeleBREX
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.
Intervention: Drug: celecoxib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
12
Same as current
July 2019
July 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Confirmed genetic diagnosis consistent with SMA that can include: SMN1 gene deletions, rearrangements and/or mutations
  2. 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).
  3. Confirmed genetic test result indicating number of SMN2 gene copies
  4. Age > 2.0 years old at screening
  5. Patients weighing at least 12 kg at screening
  6. 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)
  7. Written informed consent obtained from patient and/or parents or legal guardians

Exclusion Criteria:

  1. Clinical presentation and/or genetic testing that is not consistent with SMA type II or III
  2. Inability or unwillingness to swallow celecoxib suspension
  3. Major surgery (scoliosis repair, G-tube insertion) within past 3 months
  4. 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)
  5. Known hypersensitivity or allergy to Ora-Blend® or its excipients
  6. Demonstrated allergic-type reaction to sulfonamides
  7. Celecoxib use within 2 weeks prior to screening visit
  8. 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.
  9. Concurrent use of medication contraindicated with Celecoxib use (including but not limited to, warfarin, fluconazole, lithium, hydrochlorothiazide)
  10. Female who is pregnant or breast feeding
  11. 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.
  12. Patients participating in any pharmaceutical clinical trial (with active agent) that could impact with the results of this study
  13. Inability or refusal to provide informed consent
Sexes Eligible for Study: All
2 Years to 80 Years   (Child, Adult, Older Adult)
No
Contact: Hugh McMillan, MD 613-737-7600 ext 1605 hmcmillan@cheo.on.ca
Contact: Rosa Ramos, BioTech 613-737-7600 ext 6058 rramos@cheo.on.ca
Canada
 
 
NCT02876094
15/22E
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Yes
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.
Hugh McMillan, Children's Hospital of Eastern Ontario
Hugh McMillan
  • Families of Spinal Muscular Atrophy
  • Gwendolyn Strong Foundation
Principal Investigator: Hugh McMillan, MD Children's Hospital of Eastern Ontario Research Institute
Children's Hospital of Eastern Ontario
July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP