DNTH103 for Polyneuropathy

(CAPTIVATE Trial)

Recruiting at 75 trial locations

Overseen By Dianthus Clinical Contact Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Dianthus Therapeutics

Must be taking: Immunoglobulin, Corticosteroids

Disqualifiers: Polyneuropathy, Central demyelination, Autoimmune, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

480 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DNTH103 to determine its effectiveness for people with chronic inflammatory demyelinating polyneuropathy (CIDP), a condition causing long-term nerve damage. The study compares DNTH103 to a placebo, a substance without active medication, to assess the drug's efficacy. Participants receive various doses over time in different groups. Ideal candidates for this trial have been diagnosed with CIDP and have experienced issues such as needing regular immunoglobulin or steroid treatments, or they have not received prior treatment for CIDP. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that DNTH103 has a good safety record from earlier studies. The data suggest it could be a safer choice, with positive results supporting its safety and effectiveness. Previous trials indicated that DNTH103 is well-tolerated when administered either intravenously or subcutaneously. No major safety issues were reported, and the treatment offers a promising balance of benefits and manageable side effects. This suggests that DNTH103 could be a suitable option for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for polyneuropathy?

Researchers are excited about DNTH103 for polyneuropathy because it offers a fresh approach compared to traditional treatments like gabapentin and pregabalin. Unlike these standard options that primarily focus on symptom relief, DNTH103 is designed to potentially target the underlying mechanisms of nerve damage. It's administered via subcutaneous injection every two weeks, which might provide more consistent and sustained effects. This novel delivery method and its potential for addressing the root cause make DNTH103 a promising candidate in the fight against polyneuropathy.

What evidence suggests that DNTH103 might be an effective treatment for CIDP?

Research has shown that DNTH103, which participants in this trial may receive, may help treat conditions like chronic inflammatory demyelinating polyneuropathy (CIDP). In earlier studies, DNTH103 significantly reduced symptoms such as fatigue in people with nerve and muscle disorders. For example, one study found that fatigue levels dropped by 24.8% to 27.8%. DNTH103 also improved daily activities for patients. Although most data comes from similar conditions, these results suggest that DNTH103 could be effective for CIDP as well. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

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 have a history of nerve damage in my spinal cord.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• DNTH103

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. investor.dianthustx.com investor.dianthustx.com/news-releases/news-release-details/dianthus-therapeutics-announces-positive-data-claseprubart

Dianthus Therapeutics Announces Positive Data for ... Efficacy Results. MG-ADL. Claseprubart dosed at 300mg S.C. Q2W achieved a statistically significant and clinically meaningful mean improvement ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06858579

A Study to Evaluate the Efficacy and Safety of DNTH103 ... The purpose of this Phase 3 study is to demonstrate the efficacy of DNTH103 as compared to placebo in participants with chronic inflammatory demyelinating ...

3. investor.dianthustx.com investor.dianthustx.com/news-releases/news-release-details/dianthus-therapeutics-completes-enrollment-phase-2-magic-trial

Dianthus Therapeutics Completes Enrollment of Phase 2 ... Dianthus is building a neuromuscular franchise with DNTH103 and anticipates reporting top-line data from the Phase 2 MaGic trial in ...

4. neurologylive.com neurologylive.com/view/fda-clears-phase-2-momentum-trial-dnth103-multifocal-motor-neuropathy

FDA Clears Phase 2 MoMeNtum Trial of DNTH103 in ... MoMeNtum will evaluate the efficacy and safety of DNTH103, administered subcutaneously every two weeks over a 17-week period, followed by a 52- ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/dianthus-reveals-preclinical-data-for-its-phase-ii-neuromuscular-candidate/

Dianthus reveals preclinical data for its Phase II ... Data from the blood of three patients with gMG showed that DNTH103 reached a 24.8% – 27.8% reduction from baseline in the fatigue index, which ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06858579

A Study to Evaluate the Efficacy and Safety of DNTH103 ... The purpose of this Phase 3 study is to demonstrate the efficacy of DNTH103 as compared to placebo in participants with chronic inflammatory demyelinating ...

7. investor.dianthustx.com investor.dianthustx.com/static-files/92bea474-2ebc-43b8-918a-276b5b610e33

DNTH103, a Potentially Safer and ... This presentation is intended for non-promotional scientific purposes only and contains information on products or indications currently ...

8. investor.dianthustx.com investor.dianthustx.com/news-releases/news-release-details/dianthus-therapeutics-announces-positive-top-line-phase-1-data

Dianthus Therapeutics Announces Positive Top-line Phase ... Positive top-line Phase 1 data for lead clinical program DNTH103 confirm potent classical pathway inhibition, extended half-life, ...