Clinical Trial: The KHENERGY Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An Exploratory, Double-blind, Randomized, Placebo-controlled, Single-center, Two-way Cross-over Study With KH176 in Patients With the Mitochondrial DNA tRNALeu(UUR) m.3243A>G Mutation and Clinical

Brief Summary: Mitochondrial Diseases are rare, progressive, multi-system, often-early fatal disorders affecting both children and adults. KH176 is a novel chemical entity currently under development for the treatment of inherited mitochondrial diseases, including MELAS (Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes), MIDD (Maternally Inherited Diabetes and Deafness), Leigh's Disease and LHON (Leber's Hereditary Optic Neuropathy). The current Proof of Concept study aims to explore the effects of treatment with KH176 for 4 weeks on clinical signs and symptoms and biomarkers of mitochondrial disease and to evaluate the safety and pharmacokinetics of KH176 in patients with m.3242A>G related mitochondrial disease.

Detailed Summary:

The trial will be a double blind, randomized, placebo-controlled, single-centre, two-way cross-over trial. Twenty patients, with a confirmed mitochondrial DNA tRNALeu(UUR) m.3243A>G mutation and with clinical signs of mitochondrial disease, will be randomized over 2 groups (active or placebo first). After a screening period and a training session, each group will have 2 dosing periods of 28 days, with a washout period of at least 28 days in between. On these occasions, patients will receive 100 mg KH176 twice daily (treatment A) or a matching placebo (treatment B) twice daily for 28 days.

Clinical assessments will be performed once in a training session prior to baseline, at baseline and in week 4 post dosing during each treatment phase (A and B). Testing conditions and circumstances, with respect to timing of the assessments, hospitalization and meals, will be standardized for each assessement period. Furthermore, assessments of biomarkers for mitochondrial functioning, pharmacokinetics and specific safety assessments will be performed weekly.


Sponsor: Khondrion BV

Current Primary Outcome: Movement disorders [ Time Frame: one month ]

Rater assessed change from baseline of motoric abnormalities and movement characteristics


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • NMDAS [ Time Frame: one month ]
    Change from baseline of the Newcastle Mitochondrial Disease Activity Score
  • Spirometric parameters (FVC,FEV1, PEF) [ Time Frame: one month ]
    Change from baseline in spirometric parameters
  • Spirometric parameters (MIP, MEP) [ Time Frame: one month ]
    Change from baseline in spirometric parameters
  • Sit to Stand Test (30 seconds) [ Time Frame: one month ]
    Change from baseline assessment of the maximum number of sit-standings in 30 seconds time
  • Handgrip Dynamometry [ Time Frame: one month ]
    Change from baseline assessment of the maximum grip strenght
  • 6-min chewing test [ Time Frame: one month ]
    Change from baseline assessment in rate of mastication
  • 6-min chewing test [ Time Frame: one month ]
    Change from baseline assessment of pain and tiredness (VAS) during a 6-min chewing test
  • 6-MWT [ Time Frame: one month ]
    Change from baseline assessment of the Distance during a 6-min Walk Test
  • RAND-SF36 score [ Time Frame: one month ]
    Change from baseline in the RAND-SF36
  • HAD and BDI [ Time Frame: one month ]
    Change from baseline in the Hospital Anxiety and Depression Scale (HAD), supplemented with a Beck Depression Index (BDI)
  • BDI [ Time Frame: one month ]
    Change from baseline in the Beck Depression Index (BDI)
  • CIS [ Time Frame: one month ]
    Change from baseline in the Checklist Individual Strength
  • TAP [ Time Frame: one month ]
    Change from baseline assessment of alertness and mental flexibility during a Test of Attentional Performance (TAP)
  • Goal Attainment Scale [ Time Frame: one month ]
    Assessment of pre-defined goal attainment during each treatment period
  • Registration of Motor Activity and Sleeping pattern [ Time Frame: one month ]
    During each treatment period a continuous registration of Motor Activity and Sleeping pattern by accelerometer, assessing sleep quality, quantity and overall motor activity
  • Vital Signs [ Time Frame: one month ]
    Change from Baseline assessment of vital signs (heart rate, blood pressure)
  • ECG [ Time Frame: one month ]
    Change from Baseline assessment of ECG-intervals
  • Clinical Laboratory [ Time Frame: one month ]
    Change from Baseline assessment of Clinical Laboratory parameters
  • Pharmacokinetics of KH176 and metabolites [ Time Frame: one month ]
    Attainment of steady state and total exposure (AUC) at steady state conditions
  • Pharmacokinetics of KH176 and metabolites [ Time Frame: one month ]
    Attainment of steady state and maximal concentrations (Cmax) at steady state conditions
  • Glutathione [ Time Frame: one month ]
    Change from baseline assessment of the ratio of oxidized/reduced glutathione in blood samples (GSH/GSSG)
  • Blood biomarker FGF21 [ Time Frame: one month ]
    Change from baseline assessment of FGF21
  • Blood biomarker GDF15 [ Time Frame: one month ]
    Change from baseline assessment of GDF15
  • Blood biomarker PRDX1 [ Time Frame: one month ]
    Change from baseline assessment of PRDX1


Original Secondary Outcome: Same as current

Information By: Khondrion BV

Dates:
Date Received: September 13, 2016
Date Started: September 2016
Date Completion: May 2017
Last Updated: September 16, 2016
Last Verified: September 2016