Recruiting PHASE2 Primary Mitochondrial Disease

Tests treatment safety and results for Primary Mitochondrial Disease

Official title Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease

ClinicalTrials.gov ID: NCT05650229

What this study is testing

What is KL1333?

KL1333 is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for primary mitochondrial disease.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: The primary objective of the FALCON study is to evaluate the efficacy of KL1333 on selected disease manifestations of primary mitochondrial disease (PMD) following 48 weeks of treatment. This objective involves evaluating the efficacy of KL1333 versus placebo on fatigue symptoms and impacts on daily living as well as on functional lower extremity strength and endurance.

Phase 2: a mid-size study of how well it works
Time commitment: about 48 weeks
You might receive a placebo (an inactive treatment) instead of the study drug.

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older

You may be able to join if

Age 18 years or older.
A confirmed PMD diagnosis caused by a known pathogenic gene mutation or deletion of the mitochondrial genome (category 6 of the International...
m.3243A\>G associated MELAS-MIDD spectrum disorders,
single large scale mtDNA deletion associated KSS-CPEO spectrum disorders,
other multisystemic mtDNA-related disease (including MERRF).

You likely can't join if

Primary mitochondrial disease with predominant neurodegenerative phenotypes, such as, but not limited to, Leigh syndrome, Leber hereditary optic...
Primary mitochondrial disease nuclear DNA mutations or mutations causing mtDNA destabilisation. Genetic mtDNA variants of uncertain significance...
General fatigue or muscle weakness due to causes other than mitochondrial disease, in the opinion of the investigator.
Significant cardiovascular disease (e.g., sustained or symptomatic arrhythmia; dilated heart chambers or reduced function; Mobitz II atrioventricular...
Recent history of unstable disease, inadequately controlled neurological manifestations or not recovered from stroke-like episodes including but not...
stroke-like episodes within the last 6 months

See the full eligibility criteria

Who can join

Age 18 years or older.
A confirmed PMD diagnosis caused by a known pathogenic gene mutation or deletion of the mitochondrial genome (category 6 of the International Classification of Inborn Metabolic Disorders [ICIMD])12 according to American...
m.3243A\>G associated MELAS-MIDD spectrum disorders,
single large scale mtDNA deletion associated KSS-CPEO spectrum disorders,
other multisystemic mtDNA-related disease (including MERRF).
Presence of chronic mitochondrial fatigue:
History of mitochondrial fatigue for at least 3 months prior to the Screening Visit AND
Presence of at least moderate level of fatigue, assessed by PROMIS® Fatigue PMD Short form raw score ≥ 27 at Screening and Baseline
Presence of mitochondrial myopathy defined as:
Myopathy (proximal muscle weakness), NMDAS Section III Clinical Assessment, item 5 score ≥ 1, which reads: "minimal reduction in hip flexion and/or shoulder abduction only (e.g. MRC 4+/5)". For the inclusion only hip...
Exercise Tolerance: NMDAS Section I, item 9 score ≥ 1, which reads: "unlimited on flat - symptomatic on inclines or stairs".
Patients must be able to perform at least 2 repetitions and the maximal capacity must not exceed 17 repetitions in males or 16 repetitions in females in a 30s STS test at screening.
Clinically stable, apart from symptoms associated with the diagnosis of mitochondrial disease, at Screening and Baseline, as determined by medical history, physical examination, 12-lead ECG, vital signs measurements...
The patient is willing and able to attend study appointments within the specified time windows.
Willingness and ability to complete electronic PROs.
Willingness to maintain a stable diet during the Screening and study periods.
Patients who take any mitochondrial disease-focused vitamins or supplemental therapies, including coenzyme Q10 (CoQ10), niacin/nicotinamide (vitamin B3), and L-arginine, has been on a stable dose regimen of these for 3...
Willingness to suspend treatment with idebenone during the study.
Female patient is not pregnant and at least one of the following conditions apply:
Not a woman of childbearing potential (WOCBP)
WOCBP must agree not to try and become pregnant and use a highly effective method of contraception from the time of informed consent through at least 36 days (\~5 half-lives of KL1333 plus 30 days) after the last dose...
Male patients with female partner(s) of childbearing potential must agree to use a male condom in addition to using highly effective contraception throughout the treatment period and for 96 days after the last dose of...
Female patients must agree not to breastfeed starting at Screening and throughout the study period and for 36 days after the last dose of IMP administration.
Female patients must agree to not donate ova throughout the study period and for 36 days after the last dose of IMP administration, and male patients must agree to not donate sperm throughout the study period and for 96...

What rules you out

Primary mitochondrial disease with predominant neurodegenerative phenotypes, such as, but not limited to, Leigh syndrome, Leber hereditary optic neuropathy (LHON) and Neuropathy ataxia-retinitis pigmentosa syndrome...
Primary mitochondrial disease nuclear DNA mutations or mutations causing mtDNA destabilisation. Genetic mtDNA variants of uncertain significance, likely pathogenic, or pathogenic mutations with degrees of heteroplasmy...
General fatigue or muscle weakness due to causes other than mitochondrial disease, in the opinion of the investigator.
Significant cardiovascular disease (e.g., sustained or symptomatic arrhythmia; dilated heart chambers or reduced function; Mobitz II atrioventricular block or greater) OR abnormal ECG that is clinically significant, as...
Recent history of unstable disease, inadequately controlled neurological manifestations or not recovered from stroke-like episodes including but not limited to:
stroke-like episodes within the last 6 months
more than 1 seizure/month within the last 6 months
hospitalised for Status Epilepticus within the last 6 months
more than 4 days of migraine episodes/month within the last 6 months
History of inflammatory bowel disease, gastric erosions, peptic ulcer disease, or gastrointestinal bleeding episodes. Gastroesophageal reflux disease diagnosed by objective endoscopic or radiographic means, and...
The patient has one or more clinical laboratory test values outside the reference range, based on the blood and urine samples taken at the Screening Visit, that are of potential risk to the patient's safety, or the...
estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation \<30 mL/min/1.73 m2
a serum total bilirubin value \> 1.5 times the upper limit of the reference range unless elevation is related to Gilbert's syndrome and the investigator can rule out any underlying liver dysfunction based on other...
a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \> 2 times the upper limit of the reference range. Values between 2 and 3 times the upper limit of the reference range may be allowed if...
The patient has, in the investigator's opinion, severe ataxia, neuropathy, balance problems or other medical condition that would interfere the evaluation of the 30s STS test.
Untreated or undertreated sleep apnoea, in the opinion of the investigator.
Use of idebenone within 14 days prior to the first dose.
Patients have a history of unstable or severe pulmonary, immunological, oncological, hepatic disease, renal disease, or another medically significant illness other than PMD or takes medication that could, in the...
The patient is, in the investigator's opinion, unlikely to comply with the protocol e.g. due to cognitive impairment or is unsuitable for any reason.
The patient has an immediate family member (defined as family members residing at the same address) who participates in the study.
Female patients with a positive pregnancy result at Screening or at Baseline.
A patient cannot participate if they received an investigational drug 30 days or 5 half-lives prior to the Screening Visit (whichever is longer), or plans to use an investigational drug (other than the study...
Hypersensitivity to the active substance or to any of the excipients or placebo.

The study team makes the final eligibility decision.

Where it's taking place

Orange, California, United States
San Diego, California, United States
San Francisco, California, United States
Aurora, Colorado, United States
New Haven, Connecticut, United States
Miami, Florida, United States
Atlanta, Georgia, United States
Indianapolis, Indiana, United States
Baltimore, Maryland, United States
Rochester, Minnesota, United States
St Louis, Missouri, United States
Marlboro, New Jersey, United States
New York, New York, United States
Akron, Ohio, United States
Philadelphia, Pennsylvania, United States
Pittsburgh, Pennsylvania, United States
Flower Mound, Texas, United States
Houston, Texas, United States
Randwick, New South Wales, Australia
Saint Leonards, New South Wales, Australia

+ 28 more site(s).

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The study runs about 48 weeks per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Orange, California, United States; San Diego, California, United States; San Francisco, California, United States; Aurora, Colorado, United States; New Haven, Connecticut, United States; Miami, Florida, United States and 42 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.