A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease

Phase 1

Completed

• Conditions: MELAS Syndrome; Mitochondrial Diseases; Mitochondrial Myopathies; Mitochondrial Respiratory Chain Deficiencies
• Interventions: Drug: Placebo Oral Tablet; Drug: KL1333

• Registration Number: NCT03888716
• Lead Sponsor: Abliva AB

Brief Summary

This will be a double blind, randomised, placebo controlled, single and multiple oral dose study conducted in 3 parts: Part A, Part B and Part C. Part A and Part B include healthy volunteers only and will be completed before Part C including patients with primary mitochondrial disease will be initiated. The starting dose in the first cohort of Part A will be 25 mg. The dose level in the additional cohorts will be decided following review of data of the previous cohorts.

Detailed Description

Part A: Eight healthy subjects will be studied in a single cohort (Group A1). Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the first dose administration. Subjects will participate in 2 treatment periods, fasting or after consuming a standard high-fat breakfast. For each treatment period, subjects will reside at the Phase I clinical site from Days 1 to 3 (48 hours postdose). Subjects will return to the clinical site for outpatient visits on Days 4 and 5. There will be at least a 10 day washout between doses Additional single-dose cohorts may be enrolled based on data obtained from either Parts A or B.

Part B: Sixteen healthy subjects will be studied in 2 cohorts (Groups B1 and B2), with each cohort consisting of 8 subjects. Following review of safety, tolerability, and PK data, up to 3 additional dose cohorts of healthy subjects may be added to further explore the PK, safety, and tolerability of KL1333. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the first dose administration. All subjects will participate in 1 treatment period and will reside at the Phase I clinical site from Days -1 to 12 (48 hours post final dose). Subjects will return to the clinical site for outpatient visits on Days 13 and 14. On Day 1, 6 subjects will be randomised to receive KL1333 and 2 subjects will be randomised to receive placebo. Subjects will return for a Follow-up visit on Day 15, 5 days after their final dose.

Part C: A total of 8 patients diagnosed with any mitochondrial disease will be enrolled in this part of the study. Part C may start after the dose selection conference has been completed for the final cohort of Part B, at a daily dose no higher than the highest well-tolerated dose in Part B. Potential study patients will be screened to assess their eligibility to enter the study within 35 days prior to the first dose administration. Patients will reside at the clinical site from Days -1 to 2 and Days 10 to 11 and return to the clinical site for outpatient visits on Days 4 and 8. It is planned for patients to receive study drug once daily on Days 1 to 10. Patients will return for a Follow-up visit on Day 15, 5 days after their final dose.

Study Timeline

• Study Start: 2019-03-18
• Study First Submitted: 2019-03-19
• Study First Submitted QC: 2019-03-22
• Study First Posted: 2019-03-25
• Primary Completion: 2021-03-16
• Study Completion: 2021-03-16
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-19
• Last Update Posted: 2021-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Matching placebo	Placebo Oral Tablet	25 and 100 mg KL placebo encapsulated tablets for daily oral dosing
KL1333	KL1333	25 and 100 mg KL1333 encapsulated tablets for daily oral dosing

Primary Outcome Measures

Name	Time	Method
Safety: incidence and severity of AEs	Day 15
Safety: Number of participants with clinically significant abnormal vital signs measurements	Day 15
Safety: Number of participants with clinically significant abnormal physical examinations	Day 15
Safety: incidence of laboratory abnormalities, based on haematology, clinical chemistry, and urinalysis test results	Day 15
Safety: 12 lead ECG parameters	Day 15

Secondary Outcome Measures

Name	Time	Method
PK: area under the curve, AUC0 ∞	Day 1
PK: AUC over a dosing interval (AUC0 τ)	Days 1 and 10
PK: temporal change parameter (TCP; AUC0 τ/AUC0-∞)	Days 1 and 10
PK: Cmax	Day 1
PK: time of the Cmax (Tmax)	Day 1
PK: minimum observed plasma concentration (Cmin)	Days 1 and 10
PK: apparent plasma terminal elimination half life (t1/2)	Days 1 and 10
PK: mean residence time (MRT)	Days 1 and 10
PK: apparent total plasma clearance (CL/F)	Days 1 and 10
PK: apparent volume of distribution during the terminal phase (Vz/F)	Days 1 and 10

Trial Locations

Locations (2)

Covance Leeds; 🇬🇧 Leeds, West Yorkshire, United Kingdom

UCL; 🇬🇧 London, United Kingdom