Mitochondrial DiseasesPhase 1NCT03888716
A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
A Phase 1 study testing KL1333 in people with Mitochondrial Diseases and Mitochondrial Respiratory Chain Deficiencies, run by Abliva AB at 2 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Diseases, Mitochondrial Respiratory Chain Deficiencies, MELAS Syndrome
- What is being tested?
- KL1333
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 18 Mar 2019to 16 Mar 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy subjects and patients with mitochondrial disease must satisfy all of the following criteria at the Screening visit unless otherwise stated:
- Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
- Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
- Able to perform all protocol-specified assessments and comply with the study visit schedule.
- Additional inclusion criteria for healthy subjects:
- Males or females, of any race, between 18 and 65 years of age, inclusive.
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- Weight ≥50 kg and body mass index between 18.0 and 32.0 kg/m2, inclusive.
- 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:
- Males or females, of any race, between 18 and 75 years of age, inclusive.
- Body mass index between 15.0 and 32.0 kg/m2, inclusive.
- Any mitochondrial disease that has been genetically confirmed.
- 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.
Who cannot join
- 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:
- 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.
- History of gastroesophageal reflux disease, gastric erosions, peptic ulcer disease, or gastrointestinal bleeding episodes.
- 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).
- 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.
- 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.
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- History of alcoholism or drug/chemical abuse within 2 years prior to Screening.
- 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.
- Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Check in.
- Positive hepatitis panel and/or positive human immunodeficiency virus test
- Additional exclusion criteria for patients with mitochondrial disease:
- 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.
- 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.
- Uncontrolled diabetes mellitus, as determined by the Investigator. Creatinine clearance <45 mL/min as calculated by the Cockcroft-Gault equation
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Covance Leeds
Leeds, West Yorkshire, LS2 9LH
UCL
London
About this study
Official 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
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.
Read the 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.
- Conditions
- Mitochondrial Diseases, Mitochondrial Respiratory Chain Deficiencies, MELAS Syndrome, Mitochondrial Myopathies
- Being tested
- KL1333, Placebo Oral Tablet
- Keywords
- Mitochondrial Diseases, Mitochondrial Respiratory Chain Deficiencies, MELAS Syndrome, Mitochondrial Myopathies, Kearns-Sayre Syndrome, Ophthalmoplegia, Chronic Progressive External
- Medical subject headings
- Mitochondrial Diseases, MELAS Syndrome, Mitochondrial Myopathies, Kearns-Sayre Syndrome, Ophthalmoplegia, Chronic Progressive External
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KL1333Drug
25 and 100 mg KL1333 encapsulated tablets
Placebo Oral TabletDrug
25 and 100 mg placebo encapsulated tablets
| Study group | Role | What they receive |
|---|---|---|
| KL1333 | Experimental | 25 and 100 mg KL1333 encapsulated tablets for daily oral dosing Receives: Drug: KL1333 |
| Matching placebo | Placebo comparator | 25 and 100 mg KL placebo encapsulated tablets for daily oral dosing Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: incidence and severity of AEs
Measured: Day 15
Safety: incidence of laboratory abnormalities, based on haematology, clinical chemistry, and urinalysis test results
Measured: Day 15
Safety: 12 lead ECG parameters
Measured: Day 15
Safety: Number of participants with clinically significant abnormal vital signs measurements
Measured: Day 15
Safety: Number of participants with clinically significant abnormal physical examinations
Measured: Day 15
Secondary outcomes (10)
PK: area under the curve, AUC0 ∞
Measured: Day 1
PK: AUC over a dosing interval (AUC0 τ)
Measured: Days 1 and 10
PK: temporal change parameter (TCP; AUC0 τ/AUC0-∞)
Measured: Days 1 and 10
PK: Cmax
Measured: Day 1
PK: time of the Cmax (Tmax)
Measured: Day 1
PK: minimum observed plasma concentration (Cmin)
Measured: Days 1 and 10
PK: apparent plasma terminal elimination half life (t1/2)
Measured: Days 1 and 10
PK: mean residence time (MRT)
Measured: Days 1 and 10
PK: apparent total plasma clearance (CL/F)
Measured: Days 1 and 10
PK: apparent volume of distribution during the terminal phase (Vz/F)
Measured: Days 1 and 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2019
- Study start18 Mar 2019
- Primary completion16 Mar 2021
- Study completion16 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abliva AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Matilda Hugerth, MSc, Study director, Abliva AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03888716
- Sponsor's protocol ID
- KL1333 2018-102
- Status last verified
- Oct 2021
- First submitted
- 19 Mar 2019
- Last updated
- 20 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: According to EMA rules.
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03888716
- Acronym / sponsor ID
- KL1333 2018-102
- Conditions
- Mitochondrial Diseases, Mitochondrial Respiratory Chain Deficiencies, MELAS Syndrome, Mitochondrial Myopathies
- Keywords
- Mitochondrial Diseases, Mitochondrial Respiratory Chain Deficiencies, MELAS Syndrome, Mitochondrial Myopathies, Kearns-Sayre Syndrome, Ophthalmoplegia, Chronic Progressive External
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Abliva ABIndustry (pharma, biotech, devices)
- Study start
- 18 Mar 2019 (actual)
- Primary completion
- 16 Mar 2021 (actual)
- Study completion
- 16 Mar 2021 (actual)
- First posted
- 25 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| KL1333 | Experimental | Drug: KL133325 and 100 mg KL1333 encapsulated tablets for daily oral dosing |
| Matching placebo | Placebo comparator | Drug: Placebo Oral Tablet25 and 100 mg KL placebo encapsulated tablets for daily oral dosing |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Healthy subjects and patients with mitochondrial disease must satisfy all of the following criteria at the Screening visit unless otherwise stated:
- Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
- Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
- Able to perform all protocol-specified assessments and comply with the study visit schedule.
- Males or females, of any race, between 18 and 65 years of age, inclusive.
Key exclusion criteria (14 listed)
- 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:
- 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.
- History of gastroesophageal reflux disease, gastric erosions, peptic ulcer disease, or gastrointestinal bleeding episodes.
- 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).
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KL133325 and 100 mg KL1333 encapsulated tablets | Drug | KL1333 |
| Placebo Oral Tablet25 and 100 mg placebo encapsulated tablets | Drug | Matching placebo |
Primary outcome
Safety: incidence and severity of AEs
Time frame: Day 15
Safety: incidence of laboratory abnormalities, based on haematology, clinical chemistry, and urinalysis test results
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: Number of participants with clinically significant abnormal physical examinations
Time frame: Day 15
10 secondary outcomes
PK: area under the curve, AUC0 ∞
Time frame: Day 1
PK: AUC over a dosing interval (AUC0 τ)
Time frame: Days 1 and 10
PK: temporal change parameter (TCP; AUC0 τ/AUC0-∞)
Time frame: Days 1 and 10
PK: Cmax
Time frame: Day 1
PK: time of the Cmax (Tmax)
Time frame: Day 1
PK: minimum observed plasma concentration (Cmin)
Time frame: Days 1 and 10
PK: apparent plasma terminal elimination half life (t1/2)
Time frame: Days 1 and 10
PK: mean residence time (MRT)
Time frame: Days 1 and 10
PK: apparent total plasma clearance (CL/F)
Time frame: Days 1 and 10
PK: apparent volume of distribution during the terminal phase (Vz/F)
Time frame: Days 1 and 10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2021.
- Individual participant dataSharing planned: No. According to EMA rules.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matilda Hugerth, MSc study director
Abliva AB
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KL1333 in people with Mitochondrial Diseases and Mitochondrial Respiratory Chain Deficiencies, run by Abliva AB at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: incidence and severity of AEs (time frame: Day 15). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2021.