CTI-1601 for Friedreich's Ataxia

(Jive Trial)

Recruiting 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

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label extension (OLE) study designed to evaluate the long-term safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical effects of subcutaneous (SC) administration of CTI-1601, also known as nomlabofusp, in subjects with Friedreich's ataxia (FRDA). The objectives of this OLE study are: * To evaluate the safety of long-term subcutaneous (SC) administration of CTI-1601 in subjects with FRDA * To evaluate the PK of long-term subcutaneous (SC) administration of CTI-1601 in subjects with FRDA * To evaluate the effect of long-term subcutaneous (SC) administration of CTI-1601 in subjects with FRDA on: * Tissue FXN concentrations * Clinical evaluations of FRDA * Gene Expression and select lipids

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.

How does the drug CTI-1601 differ from other treatments for Friedreich's Ataxia?

CTI-1601 is unique because it is designed to deliver frataxin protein directly to the mitochondria, potentially addressing the root cause of Friedreich's Ataxia by increasing frataxin levels, unlike other treatments that may not target this specific mechanism. ^{1 2 3 4 5}

Research Team

Larimar Therapeutics, Inc.

Principal Investigator

Larimar Therapeutics, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Identification of a novel missense mutation in Friedreich's ataxia -FXNW 168R. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Mutation of the start codon in the FRDA1 gene: linkage analysis of three pedigrees with the ATG to ATT transversion points to a unique common ancestor. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Upregulation of expression from the FRDA genomic locus for the therapy of Friedreich ataxia. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Frequency and Genetic Profile of Compound Heterozygous Friedreich's Ataxia Patients-the Brazilian Experience. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

A review of Friedreich ataxia clinical trial results. [2012]