CTI-1601 for Friedreich's Ataxia

(Jive Trial)

Enrolling by invitation at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Larimar Therapeutics, Inc.

Must not be taking: Amiodarone, Erythropoietin, Etravirine, others

Disqualifiers: Cardiac condition, Investigational drug, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called CTI-1601, designed to help individuals with Friedreich's ataxia, a genetic disorder affecting movement and coordination. The research aims to ensure the treatment's long-term safety, understand how the body processes it, and observe its effects on specific proteins, genes, and fats. Eligible participants must have previously taken part in a CTI-1601 study without experiencing major health issues from the treatment and must be able to administer daily injections or have a caregiver who can. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as amiodarone, erythropoietin, etravirine, gamma interferon, and high doses of biotin. You must also have been on a stable dose of your current medications for at least 28 days before the trial.

Is there any evidence suggesting that CTI-1601 is likely to be safe for humans?

Research has shown that CTI-1601, also known as nomlabofusp, is being tested for safety in treating Friedreich's ataxia. In earlier studies, some participants experienced a severe allergic reaction called anaphylaxis. Specifically, this occurred in 7 people, mostly in an open-label study. The FDA recommends monitoring at least 30 participants for six months to gather more safety data. While testing continues, the risk of anaphylaxis remains an important safety concern. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Friedreich's ataxia?

CTI-1601 is unique because it directly addresses the root cause of Friedreich's Ataxia by delivering frataxin, a protein that patients with this condition lack due to a genetic mutation. Unlike current treatments that mainly manage symptoms, CTI-1601 aims to increase frataxin levels in the body, potentially slowing or even halting disease progression. Researchers are excited about this treatment because it targets the disease at a molecular level, offering hope for more effective management of Friedreich's Ataxia beyond symptomatic relief.

What evidence suggests that CTI-1601 might be an effective treatment for Friedreich's ataxia?

Research has shown that CTI-1601, the investigational treatment studied in this trial, might help treat Friedreich's Ataxia by increasing levels of frataxin, a protein lacking in people with this condition. In earlier studies, patients taking CTI-1601 had more frataxin in their skin cells within two weeks. This increase is important because higher frataxin levels might alleviate symptoms like balance and stability issues. The treatment works by replacing frataxin, directly targeting the disease's root cause. Early findings suggest that CTI-1601 could stabilize or improve some symptoms of Friedreich's Ataxia, but further research is needed to confirm these effects. ^{1 3 6 7 8}

Who Is on the Research Team?

Larimar Therapeutics, Inc.

Principal Investigator

Larimar Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with Friedreich's Ataxia, a genetic movement disorder. Participants must have completed a prior CTI-1601 study to join this extension and continue evaluating the drug's effects.

Inclusion Criteria

I can self-inject my medication or have someone who can do it for me.

Subject has a HbA1c less than or equal to 7.0%

Subjects with FRDA who previously completed participation in a study of CTI-1601 will be eligible to participate in this study unless the subject experienced one or more of the following in a previous CTI-1601 study: a) serious adverse event (SAE) related to study drug; b) significant AE, defined as Grade 3 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (or higher), related to study drug; c) some other event, related to participation in a previous study with CTI-1601, that supports the exclusion of the subject from participating in this study as determined by the Sponsor (i.e., an AE considered clinically significant by the Sponsor regardless of whether it met SAE criteria and regardless of CTCAE grade); d) Withdraw from participation in a previous study of CTI-1601 for any reason

Exclusion Criteria

I take medication that is injected into my abdomen or thigh.

Subject has a Screening echocardiogram (ECHO) LVEF < 45%

I take more than 30 mcg/day of biotin or have changed my biotin dose in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily subcutaneous administration of CTI-1601

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive CTI-1601 to evaluate long-term safety, efficacy, and pharmacokinetics

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• CTI-1601

Trial Overview The trial tests long-term safety and effects of CTI-1601, administered under the skin, on disease symptoms, gene expression, and specific lipid levels in patients with Friedreich's Ataxia.

How Is the Trial Designed?

Group I: CTI-1601 Experimental Treatment 1 Intervention

CTI-1601 will be administered daily

Who Is Running the Clinical Trial?

Larimar Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

270+

Published Research Related to This Trial

A new cellular assay was developed to measure frataxin expression from the FRDA gene, which is crucial for identifying potential treatments for Friedreich ataxia, a neurodegenerative disease affecting motor function.

The study successfully created fusion proteins of frataxin and enhanced green fluorescent protein (EGFP), allowing researchers to visualize and enhance FRDA gene expression, which could lead to the discovery of pharmacological agents that improve frataxin levels in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upregulation of expression from the FRDA genomic locus for the therapy of Friedreich ataxia. Sarsero, JP., Li, L., Wardan, H., et al.[2023]

The study identifies a novel missense mutation, frataxinW168R, in Friedreich's ataxia patients, which results in the production of an intermediate form of frataxin that does not mature properly, indicating a specific defect in frataxin processing.

Despite the frataxinW168R being localized to mitochondria, increasing levels of the precursor form do not enhance the production of the mature frataxin, suggesting that new therapeutic strategies are needed to address this processing issue for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a novel missense mutation in Friedreich's ataxia -FXNW 168R. Clark, E., Strawser, C., Schadt, K., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06447025

An Open Label Extension Study of CTI-1601 in Subjects ... A higher score indicates a better outcome, reflecting greater stability and balance abilities while standing upright. Through study completion, up to 24 months.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10963286/

Safety, pharmacokinetics, and pharmacodynamics of ... Nomlabofusp (previously CTI‐1601) is a frataxin replacement therapy with a unique mechanism of action that directly addresses this underlying frataxin ...

3. ataxia.org.uk ataxia.org.uk/research-news/larimar-therapeutics-announces-progress-of-the-cti-1601-trial-for-friedreichs-ataxia/

Larimar Therapeutics announces progress of the ... At Day 14, all patients with quantifiable levels of FXN at baseline and Day 14 treated with 50 mg of CTI-1601 achieved FXN levels in skin cells ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04176991

Single Ascending Dose Study of CTI-1601 Versus Placebo ... Study Overview. Brief Summary. To evaluate the safety and tolerability of single ascending doses of CTI-1601 in participants with Friedreich's ataxia.

5. investors.larimartx.com investors.larimartx.com/static-files/9599c52a-bcbc-4db7-b4af-99235d4c1d6d

Forward-Looking Statements - Larimar Therapeutics ... data and testing of CTI-1601 may not be predictive of the results or success of later clinical trials, and assessments; the ongoing impact ...

6. curefa.org curefa.org/drug-development/nomlabofusp-cti-1601/

Nomlabofusp (CTI-1601) Safety data were also reported. Anaphylaxis (a severe allergic reaction) has been reported in 7 participants in the OL study, with most events occurring on ...

7. investors.larimartx.com investors.larimartx.com/news-releases/news-release-details/larimar-therapeutics-announces-fda-recommendations-safety

Larimar Therapeutics Announces FDA Recommendations on ... Safety Database: FDA recommended to evaluate safety in at least 30 participants with continuous study drug exposure for 6-months and a subset of ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/acn3.51971

Safety, pharmacokinetics, and pharmacodynamics of ... Nomlabofusp (previously CTI-1601) is a frataxin replacement therapy with a unique mechanism of action that directly addresses this underlying frataxin ...