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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02876094
• Date of registration: 09/08/2016
• Prospective Registration: Yes
• Primary sponsor: Hugh McMillan
• Public title: Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy SMA
• Scientific title: A Pilot, Open-Label, Dose Response Study Investigating the Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy (SMA)
• Date of first enrolment: January 29, 2019
• Target sample size: 1
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02876094
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada

Contacts

• Name: Hugh McMillan, MD
• Affiliation: Children's Hospital of Eastern Ontario Research Institute

Key inclusion & exclusion criteria

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



Age minimum: 2 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy (SMA)

Intervention(s)

Drug: celecoxib

Primary Outcome(s)

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]

Secondary Outcome(s)

Eligibility Measured by Number of Screen Failures [Time Frame: 4 weeks post]

Safety Profile Measured by Adverse Event Frequency,Type and Severity [Time Frame: 4 weeks post]

Delivery Time of Shipped Samples Assessed by Viability [Time Frame: 4 weeks post]

Recruitment Plan Measured by Number of Potentially Eligible Subjects [Time Frame: 4 weeks post]

Compliance Measured by Reported Protocol Deviations [Time Frame: 4 weeks post]

Secondary ID(s)

15/22E

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Families of Spinal Muscular Atrophy

Gwendolyn Strong Foundation