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

• Status: Completed
• Trial end date: 2021-03-16
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Abliva AB; NeuroVive Pharmaceutical AB

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