DNTH103 for Polyneuropathy

(CAPTIVATE Trial)

Recruiting at 7 trial locations

Overseen By Dianthus Clinical Contact Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Dianthus Therapeutics

Must be taking: Immunoglobulin, Corticosteroids

Disqualifiers: Polyneuropathy, Central demyelination, Autoimmune, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this Phase 3 study is to demonstrate the efficacy of DNTH103 as compared to placebo in participants with chronic inflammatory demyelinating polyneuropathy (CIDP).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants can be currently treated with certain medications like immunoglobulin or corticosteroids, so you might be able to continue those.

How does the treatment DNTH103 differ from other treatments for polyneuropathy?

DNTH103 is unique because it involves gene therapy using neurotrophin 3 (NT-3), which supports nerve cell survival and repair, potentially offering a novel approach to treating polyneuropathy by promoting nerve regeneration and reducing inflammation, unlike traditional treatments that mainly focus on symptom management. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), a nerve disorder. Participants should meet specific health criteria, but the provided information doesn't detail these requirements.

Inclusion Criteria

I am a male who is either surgically sterile or will not donate sperm and will use contraception if my partner can get pregnant.

Must have given written informed consent before any study-related activities are carried out.

I haven't had any recent neurological events affecting my health.

Exclusion Criteria

Prior history of N. meningitidis infection.

I do not have any health conditions that would prevent me from joining this study.

I have a history of nerve damage in my spinal cord.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Treatment (Part A)

Participants receive DNTH103 intravenously on Day 1, followed by subcutaneous administration every 2 weeks for up to 13 weeks

13 weeks

Randomized, Double-Blind Treatment (Part B)

Participants who respond in Part A are randomized to receive either DNTH103 or placebo subcutaneously every 2 weeks for up to 52 weeks

52 weeks

Optional Open-label Extension (OLE)

Eligible participants may continue to receive DNTH103 subcutaneously every 2 weeks for up to 104 weeks

104 weeks

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

40 weeks

Treatment Details

Interventions

• DNTH103 (Monoclonal Antibodies)

Trial Overview The study tests DNTH103's effectiveness and safety against a placebo in treating CIDP. It's a Phase 3 trial, which means it's one of the final steps before potential approval if results are positive.

Participant Groups

Group I: DNTH103 Low Dose (Part B) Experimental Treatment 1 Intervention

DNTH103 SC once every 2 weeks for up to 52 weeks.

Group II: DNTH103 High Dose (Part B) Experimental Treatment 1 Intervention

DNTH103 SC once every 2 weeks for up to 52 weeks.

Group III: DNTH103 (Part A) Experimental Treatment 1 Intervention

DNTH103 intravenous (IV) loading dose on Day 1. DNTH103 subcutaneous (SC) once every 2 weeks for up to 13 weeks.

Group IV: DNTH103 (Optional OLE) Experimental Treatment 1 Intervention

DNTH103 SC once every 2 weeks for up to 104 weeks.

Group V: Placebo (Part B) Placebo Group 1 Intervention

Placebo SC once every 2 weeks for up to 52 weeks.

Who Is Running the Clinical Trial?

Dianthus Therapeutics

Lead Sponsor

Trials

3

Recruited

580+

Findings from Research

In a study using a spontaneous autoimmune peripheral polyneuropathy (SAPP) model in mice, treatment with Neurotrophin 3 (NT-3) led to significant improvements in hind limb grip strength and nerve function, indicating its potential efficacy for conditions like chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

NT-3 treatment resulted in a 1.9 times increase in myelinated fiber density and a significant reduction in demyelinated axons, alongside decreased inflammation in the sciatic nerve, suggesting that NT-3 not only supports nerve repair but also has anti-inflammatory properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AAV1.NT-3 gene therapy attenuates spontaneous autoimmune peripheral polyneuropathy. Yalvac, ME., Arnold, WD., Braganza, C., et al.[2018]

The study identified a specific genetic variant (c.110G>C, p.Arg37Pro) in the HINT1 gene associated with a distinct phenotype in 10 patients, characterized by early onset distal weakness, muscle stiffness, and neuromyotonia, which serves as a key diagnostic feature.

Ultrasound examinations revealed reduced muscle volume and signs of nerve dysfunction, such as fasciculations and fibrillations, without structural changes in the nerves, highlighting the importance of ultrasonographic evaluation in diagnosing HINT1-related neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The most common European HINT1 neuropathy variant phenotype and its case studies. Rozevska, M., Rots, D., Gailite, L., et al.[2023]

Intramuscular injection of a recombinant adenovirus encoding NT-3 (AdNT-3) effectively prevented nerve conduction slowing in rat models of diabetic neuropathy and axonal neuropathy, indicating its potential as a treatment for these conditions.

AdNT-3 treatment was well tolerated with minimal side effects, suggesting that this gene therapy approach could provide a safe and effective method for delivering neurotrophic factors to combat peripheral neuropathies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous delivery of neurotrophin 3 by gene therapy has a neuroprotective effect in experimental models of diabetic and acrylamide neuropathies. Pradat, PF., Kennel, P., Naimi-Sadaoui, S., et al.[2013]

Peripheral neuropathy, particularly distal symmetric polyneuropathy (DN), affects up to half of diabetes patients and can lead to significant morbidity and mortality, highlighting the need for early diagnosis and preventive measures.

Currently, there is no established treatment for DN beyond improving blood sugar control, and less than one-third of patients with painful DN find relief with existing medications, indicating a need for more targeted therapies and large clinical trials to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management. Jensen, TS., Karlsson, P., Gylfadottir, SS., et al.[2023]

Neurotrophin 3 gene transfer therapy significantly improved functional and electrophysiological outcomes in a mouse model of Charcot-Marie-Tooth disease type-2D (GarsP278KY/+), enhancing myelin thickness and neuromuscular junction integrity after 12 weeks.

The therapy also addressed mitochondrial dysfunction in muscle, suggesting that neurotrophin 3 could be a promising treatment for various subtypes of Charcot-Marie-Tooth disease linked to aminoacyl-tRNA synthetase mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AAV1.NT-3 gene therapy in a CMT2D model: phenotypic improvements in GarsP278KY/+ mice. Ozes, B., Moss, K., Myers, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

AAV1.NT-3 gene therapy attenuates spontaneous autoimmune peripheral polyneuropathy. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The most common European HINT1 neuropathy variant phenotype and its case studies. [2023]

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

Continuous delivery of neurotrophin 3 by gene therapy has a neuroprotective effect in experimental models of diabetic and acrylamide neuropathies. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management. [2023]

5. England pubmed.ncbi.nlm.nih.gov

AAV1.NT-3 gene therapy in a CMT2D model: phenotypic improvements in GarsP278KY/+ mice. [2021]