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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 November 2021
• Main ID: NCT03888716
• Date of registration: 19/03/2019
• Prospective Registration: No
• Primary sponsor: Abliva AB
• Public title: A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
• Scientific title: A Phase Ia/Ib, Multiple-site Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KL1333 After a Single and Multiple Ascending Oral Doses in Healthy Subjects and Patients With Primary Mitochondrial Disease
• Date of first enrolment: March 18, 2019
• Target sample size: 72
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03888716
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United Kingdom

Contacts

• Name: Matilda Hugerth, MSc
• Affiliation: Abliva AB

Key inclusion & exclusion criteria

Inclusion Criteria (selected):

Healthy subjects and patients with mitochondrial disease must satisfy all of the following
criteria at the Screening visit unless otherwise stated:

1. Females will not be pregnant or lactating, and females of childbearing potential and
males will agree to use contraception.

2. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

3. Able to perform all protocol-specified assessments and comply with the study visit
schedule.

Additional inclusion criteria for healthy subjects:

4. Males or females, of any race, between 18 and 65 years of age, inclusive.

5. Weight =50 kg and body mass index between 18.0 and 32.0 kg/m2, inclusive.

6. In good health, determined by no clinically significant findings from medical history,
physical examination, 12 lead ECG, vital signs measurements, and clinical laboratory
evaluations (congenital nonhaemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is
not acceptable) at Screening and Check in as assessed by the Investigator.

Additional inclusion criteria for patients with mitochondrial disease:

7. Males or females, of any race, between 18 and 75 years of age, inclusive.

8. Body mass index between 15.0 and 32.0 kg/m2, inclusive.

9. Any mitochondrial disease that has been genetically confirmed.

10. Clinically stable, apart from symptoms associated with the diagnosis of mitochondrial
disease, as determined by medical history, physical examination, 12 lead ECG, vital
signs measurements, and clinical laboratory evaluations at Screening and Check-in as
assessed by the Investigator.

Exclusion Criteria (selected):

Healthy subjects and patients with mitochondrial disease will be excluded from the study if
they satisfy any of the following criteria at the Screening visit unless otherwise stated:

1. History of significant hypersensitivity, intolerance, or allergy to any drug compound,
food, or other substance, including KL1333 or its excipients, unless approved by the
Investigator.

2. History of gastroesophageal reflux disease, gastric erosions, peptic ulcer disease, or
gastrointestinal bleeding episodes.

3. History of stomach or intestinal surgery or resection that would potentially alter
absorption and/or excretion of orally administered drugs including cholecystectomy
(uncomplicated appendectomy and hernia repair will be allowed).

4. History of malignancy of any organ system other than localised basal cell carcinoma of
the skin, treated or untreated, within 5 years prior to Screening, regardless of
whether there is evidence of local recurrence or metastases.

5. History of clinically significant illness (except for mitochondrial disease in the
patients in Part C) or surgery within 4 weeks prior to Screening, as determined by the
Investigator.

6. History of alcoholism or drug/chemical abuse within 2 years prior to Screening.

7. Alcohol consumption of >28 units per week for males and >21 units per week for
females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL)
of wine, or 1/6 gill (25 mL) of spirits.

8. Positive alcohol breath test result or positive urine drug screen (confirmed by
repeat) at Screening or Check in.

9. Positive hepatitis panel and/or positive human immunodeficiency virus test

Additional exclusion criteria for patients with mitochondrial disease:

1. Use of idebenone or medications (prescription or nonprescription) that have effects on
metabolism or unknown binding sites (eg, vitamin E, co-enzyme 10, arginine) within 35
days or 5 half-lives, whichever is longer, prior to the first dose.

2. Use of prescription drugs within 14 days prior to dosing, with the exception of
established therapy for mitochondrial disease and the treatment of associated
disorders that has been stable for at least 7 days prior to the first dose, as
approved by the Medical Monitor and Investigator, in consultation with the Sponsor.

3. Uncontrolled diabetes mellitus, as determined by the Investigator. Creatinine
clearance <45 mL/min as calculated by the Cockcroft-Gault equation



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Mitochondrial Myopathies

MELAS Syndrome

Mitochondrial Respiratory Chain Deficiencies

Mitochondrial Diseases

Intervention(s)

Drug: KL1333

Drug: Placebo Oral Tablet

Primary Outcome(s)

Safety: incidence of laboratory abnormalities, based on haematology, clinical chemistry, and urinalysis test results [Time Frame: Day 15]

Safety: Number of participants with clinically significant abnormal physical examinations [Time Frame: Day 15]

Safety: 12 lead ECG parameters [Time Frame: Day 15]

Safety: Number of participants with clinically significant abnormal vital signs measurements [Time Frame: Day 15]

Safety: incidence and severity of AEs [Time Frame: Day 15]

Secondary Outcome(s)

PK: temporal change parameter (TCP; AUC0 t/AUC0-8) [Time Frame: Days 1 and 10]

PK: apparent total plasma clearance (CL/F) [Time Frame: Days 1 and 10]

PK: area under the curve, AUC0 8 [Time Frame: Day 1]

PK: AUC over a dosing interval (AUC0 t) [Time Frame: Days 1 and 10]

PK: mean residence time (MRT) [Time Frame: Days 1 and 10]

PK: minimum observed plasma concentration (Cmin) [Time Frame: Days 1 and 10]

PK: apparent volume of distribution during the terminal phase (Vz/F) [Time Frame: Days 1 and 10]

PK: apparent plasma terminal elimination half life (t1/2) [Time Frame: Days 1 and 10]

PK: time of the Cmax (Tmax) [Time Frame: Day 1]

PK: Cmax [Time Frame: Day 1]

Secondary ID(s)

KL1333 2018-102

Source(s) of Monetary Support

Please refer to primary and secondary sponsors