What is the mechanism of action of this treatment?

NAD+ modulators, such as KL1333, work by increasing the levels of NAD+, a vital coenzyme involved in cellular energy production. This enhancement of NAD+ levels can improve mitochondrial function, boost energy output, and reduce oxidative stress. For patients with mitochondrial diseases, these treatments are crucial as they target the fundamental problem of impaired energy production, potentially alleviating symptoms and improving overall cellular function and quality of life.

What side effects are associated with this type of intervention?

Common treatments for mitochondrial diseases, including those similar to the investigational NAD+ modulator KL1333, often aim to enhance cellular energy production. Known side effects of these treatments can include gastrointestinal disturbances such as nausea, vomiting, and diarrhea, as well as potential liver enzyme abnormalities. Specific to NAD+ modulators, side effects may also include flushing, itching, and mild gastrointestinal symptoms.

What prior FDA approvals exist?

There are currently no FDA-approved treatments specifically for mitochondrial diseases that function as NAD+ modulators like KL1333. The treatment landscape for mitochondrial diseases primarily involves supportive care and symptom management, as well as investigational therapies under clinical trials. KL1333 is being studied for its potential to improve fatigue and functional strength in patients with primary mitochondrial disease, but it has not yet received FDA approval.

What other types of research exist?

Promising alternatives to KL1333 for mitochondrial diseases in 2024 may include other NAD+ modulators such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Additionally, treatments that enhance mitochondrial biogenesis and function, such as PQQ (pyrroloquinoline quinone) and Coenzyme Q10, could be considered. Patients should discuss these options with their healthcare provider to determine the most appropriate treatment plan.

← Back to Search

Other

KL1333 for Mitochondrial Disease (FALCON Trial)

Phase 2

Waitlist Available

Led By Amel Karaa, MD

Research Sponsored by Abliva AB

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Presence of mitochondrial myopathy defined as myopathy (proximal muscle weakness) or limited exercise tolerance

Confirmed PMD diagnosis caused by a known pathogenic gene mutation or deletion of the mitochondrial genome according to ACMG/AMP criteria, with multisystemic disease expressions

Must not have

Primary mitochondrial disease with predominant neurodegenerative phenotypes

Primary mitochondrial disease nuclear DNA mutations or mutations causing mtDNA destabilisation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 48 weeks

Summary

This trial is testing KL1333, a new medicine, to see if it can help people with mitochondrial disease feel less tired and improve their physical abilities. The study targets people with primary mitochondrial disease because they often suffer from severe fatigue. KL1333 works by boosting energy production in cells.

Who is the study for?

Adults over 18 with primary mitochondrial disease (PMD) characterized by muscle weakness or limited exercise tolerance, chronic fatigue, and a confirmed genetic diagnosis. Participants must be clinically stable, able to attend appointments, willing to maintain diet and therapy regimens, not pregnant, and agree to contraception requirements.

What is being tested?

The FALCON study is testing the effectiveness of KL1333 on fatigue symptoms and daily life impact in PMD patients after 48 weeks compared to a placebo. It also measures lower extremity strength/endurance while assessing safety and tolerability of KL1333.

What are the potential side effects?

While specific side effects are not listed here for KL1333 or the placebo, typically such trials monitor for any adverse reactions ranging from mild discomforts like headaches or nausea to more serious issues affecting organ function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have muscle weakness or struggle with physical activity due to mitochondrial myopathy.

Select...

I have a confirmed PMD diagnosis with symptoms affecting multiple systems in my body.

Select...

I am not pregnant and follow the required birth control measures.

Select...

I am 18 years old or older.

Select...

I often feel very tired.

Select...

I am willing to stop taking idebenone for the study.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have a mitochondrial disease mainly affecting my nervous system.

Select...

I have a genetic mutation linked to mitochondrial disease.

Select...

I haven't taken any experimental drugs within the last 30 days.

Select...

I have not fully recovered from recent severe illness or stroke-like episodes.

Select...

My lab tests show values that could be risky for my health.

Select...

I do not have severe or unstable lung, immune system, liver, kidney diseases, or other serious illnesses.

Select...

I have sleep apnea that hasn't been treated or is under-treated.

Select...

I have heart disease or an abnormal heart test result.

Select...

I am not pregnant.

Select...

I have a history of stomach issues or acid reflux.

Select...

I do not have severe balance or nerve problems that would affect my ability to perform a sit-to-stand test.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 48 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~48 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 48 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in 30 Second Site-to-Stand Test.

Change in-patient-reported fatigue symptoms and impacts on daily living measured by Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue PMD Short Form

Secondary study objectives

Change from baseline in Glycated haemoglobin (HbA1c) for subjects with diabetes

Change in Clinician Global Impression of Severity

Change in Individual Activity Assessments - Interference

+6 more

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: KL1333Experimental Treatment1 Intervention

Twice daily

Group II: Matching PlaceboPlacebo Group1 Intervention

Twice daily

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

KL1333

2019

Completed Phase 1

~90

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

NAD+ modulators, such as KL1333, work by increasing the levels of NAD+, a vital coenzyme involved in cellular energy production. This enhancement of NAD+ levels can improve mitochondrial function, boost energy output, and reduce oxidative stress. For patients with mitochondrial diseases, these treatments are crucial as they target the fundamental problem of impaired energy production, potentially alleviating symptoms and improving overall cellular function and quality of life.