Bertini 2017.

Methods	Randomised, placebo‐controlled, double‐blind trial
Participants	165 non‐ambulatory participants with SMA types II or IIIa aged 3–25 years Inclusion criteria: genetic diagnosis of SMA with homozygous deletion of SMN1 exon 7, or a heterozygous deletion accompanied by a point mutation on the other allele MFM relative score (percentage of the maximum sum of both dimensions) of ≥ 15% (functional domain 1 (D1) plus functional domain 2 (D2) score) HFMS score at baseline 3–38 (non‐ambulatory); onset of symptoms at ≤ 3 years of age ability to take the study treatment (tested at screening after informed consent) Exclusion criteria: evidence of renal dysfunction, blood dysplasia, hepatic insufficiency, symptomatic pancreatitis congenital heart defect history of metabolic acidosis hypertension significant central nervous system impairment, or neurodegenerative or neuromuscular disease other than SMA any clinically significant ECG abnormality use of medications intended for the treatment of SMA inability to meet study visit requirements or co‐operate reliably with functional testing surgical spinal rod or fixation for scoliosis within the past 6 months or anticipated need of rod or fixation within 6 months of enrolment
Interventions	Oral liquid olesoxime (TRO19622: cholest‐4‐en‐3‐one, oxime) 10 mg/kg once a day or placebo Treatment duration: 24 months
Outcomes	Primary outcome: change over 24 months in functional outcome score D1+D2 of MFM Secondary outcomes: change in total MFM score, HFMS, electrophysiological measures (CMAP and MUNE), pulmonary function (FVC), quality of life (PedsQL), and Global Clinical Impression from baseline, responder analysis of MFM, laboratory assessments, ECG and adverse events
Funding	AFM‐Téléthon and Trophos SA (a wholly owned member of the Hoffmann La Roche Group since 2015)
Conflicts of interest	Several investigators declared grants and consultancy fees from Hoffmann La Roche, Trophos and other commercial entities. 8 investigators were current or former employees of Trophos or Hoffmann La Roche, 3 were stockholders and 2 authors were named on a patent pending for olesoxime. Roche also funded medical writing support.
Notes	ClinicalTrials.gov id: NCT01302600
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly assigned, centrally generated with validated randomisation software (SAS version 9.2).
Allocation concealment (selection bias)	Low risk	Computer‐generated allocation by independent statistician.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of participants and all investigators, site personal and sponsor study personal was ensured.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding of participants and all investigators, site personal and sponsor study personal was ensured.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	17 participants withdrew for unknown reasons.
Selective reporting (reporting bias)	High risk	Data were dichotomised post hoc. Investigators were employees of the pharmaceutical company and they were involved in data collection and analysis.
Other bias	High risk	Primary outcome measure was used in 2 different forms (MFM‐32 and MFM‐20) and, therefore, not truly comparable. Treatment groups have differences in included age ranges.