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Table 1 Outcome measures to be employed for evaluating the effect of sonlicromanol on the study objectives

From: A randomised placebo-controlled, double-blind phase II study to explore the safety, efficacy, and pharmacokinetics of sonlicromanol in children with genetically confirmed mitochondrial disease and motor symptoms (“KHENERGYC”)

Objective

Outcome measure

Comments

Reference

Primary outcome measure

 Gross motor symptoms of the genetic PMD in children

Gross Motor Function Measure −88 (GMFM-88)

• 88 items, 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running, and jumping.

• 4-point Likert scale.

[25]

Secondary outcome measures

 Fine manual dexterity

9-Hole Peg Test (NHPT)

• Practice session at the screening visit.

[26]

 The physical ability of the patient

10 Meter Walk Test (10MWT)

• 7-point scale ranging from total assistance to no assistance for walking/running.

[27, 28]

 Muscle spasticity

Modified Tardieu Scale for Spasticity (MTS)

• Quality (on a 5-grade scale) and angle of muscle reaction.

[29]

 Dystonia

Barry-Albright Dystonia Scale (BAD)

• 8 body parts will be evaluated: eyes, mouth, neck, trunk, and four limbs.

• 5-point ordinal scale.

[30]

 Ataxia

Scale for the Assessment and Rating of Ataxia (SARA)

• 8 items: gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test.

[31]

 Disability

Paediatric Evaluation of Disability Inventory (PEDI-CAT)

• Interview-based

• 3 main domains: responsibility (51 items, 5-point scale), mobility (75 items), and social/cognitive ability (60 items, 4-point scale).

[32]

 PMD signs and symptoms

International Paediatric Mitochondria Disease Scale (IPMDS)

• 3 domains of the disease: complaints and symptoms (23 items), physical examination (21 items), and functional tests (13 items, some are only for children ≥6 years).

[33]

 Caregiver’s burden

ZARIT-12 Burden Scale

• Ranges from ‘not at all’ to ‘extremely’.

[34]

    Quality of life

Neuro Quality of life Fatigue-Short Form (NeuroQL-SF) Paediatric version

• Physical, mental, and social effects.

• 8-item self-assessment questionnaire recommended for children of 8–17 years.

[35, 36]

 Clinician’s perception or improvement or worsening of the PMD

Clinician-scored Global Impression of Change (CGIC)

• 7-point Likert scale.

[36, 37]

 Patient’s perception of change due to intervention

Patient/Caregiver scored Global Impression of Change (PGIC)

• 7-point Likert scale.

• Will be completed by 12–18-year-old children.

• For children younger than 12 years or cognitively disabled, parents/caregivers will be completing the test.

[36, 38]

 Patient/Caregiver scored impression of change on patient-identified 3 most bothersome symptoms caused by PMD

Most Bothersome Symptom Assessment (MBSA)

• 7-point Likert scale.

• Will be completed by 12–18-year-old children.

• For children younger than 12 years or cognitively disabled, parents/caregivers will be completing the test.

[36]

 Growth

Growth

• Overall body growth will be measured (height, weight, head circumference, and weight-for-height).

 

Additional outcome measures

 Health Economics and Outcomes Research

EQ-5D-Y (Proxy 1)

• HRQoL via 5 dimensions: mobility, self-care, daily activities, pain/discomfort, and anxiety/depression.

• Each dimension will have 5 levels: no, slight, moderate, severe, and extreme problems.

[39, 40]

Health Utilities Index (HUI)

• Comprehensive health status and HRQoL.

[41, 42]

 Acceptability of sonlicromanol

Entry in the diary by the parent/caregiver

• Evaluation will be based on whether the patient has swallowed the complete dose, spat out part of the dose, or refused to take the dose.

[43]

 Palatability of sonlicromanol

Facial Hedonic Scale/Visual Analogue Scale-5 (FHS/VAS-5)

 

[43]

  1. PMD Primary Mitochondrial Diseases, GMFM-88 Gross Motor Function Measure −88, NHPT 9-Hole Peg Test, 10MWT 10 Meter Walk Test, MTS Modified Tardieu Scale for Spasticity, BAD Barry-Albright Dystonia Scale, SARA Scale for the Assessment and Rating of Ataxia, PEDI-CAT Paediatric Evaluation of Disability Inventory, IPMDS International Paediatric Mitochondria Disease Scale, NeuroQL-SF Neuro Quality of life Fatigue-Short Form, HRQoL health-related quality of life, CGIC Clinician-scored Global Impression of Change, PGIC Patient/Caregiver scored Global Impression of Change, MBSA Most Bothersome Symptom Assessment, HUI Health Utilities Index, FHS/VAS-5 Facial Hedonic Scale/Visual Analogue Scale-5, EQ-5D-Y EuroQol 5D youth version proxy version 1