DNTH103 for Neuropathy

(MOMENTUM Trial)

Recruiting at 24 trial locations

Overseen By Sankalp Gokhale

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dianthus Therapeutics

Must be taking: Ig treatment

Must not be taking: Rituximab, Cyclophosphamide, others

Disqualifiers: Autoimmune disorders, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 17 weeks

36 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 for individuals with multifocal motor neuropathy (MMN), a condition that causes muscle weakness. The trial aims to assess the safety and effectiveness of DNTH103 at various doses compared to a placebo (a substance with no active medicine). Individuals managing MMN with stable immunoglobulin (Ig) treatment might be suitable candidates. The goal is to determine if DNTH103 can manage symptoms more effectively than existing treatments. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used certain medications like rituximab, cyclophosphamide, mycophenolate mofetil, azathioprine, or cyclosporine within 6 months before joining. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that DNTH103 is likely to be safe for humans?

Research has shown that DNTH103 has promising safety results from earlier studies. Most people tolerated the treatment well, experiencing no serious side effects. Both high and low doses proved safe, indicating that participants generally managed the treatment without major problems.

This study focuses on multifocal motor neuropathy, a nerve disorder, but DNTH103 has also been tested for other conditions. These results suggest that DNTH103 could be safe for those considering joining the trial. ^{1 2 3 4 5}

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

Researchers are excited about DNTH103 for treating neuropathy because it offers a unique approach compared to existing treatments like gabapentin and duloxetine, which primarily focus on symptom relief by altering neurotransmitter activity. Unlike these standard medications, DNTH103 potentially targets the underlying pathways responsible for nerve damage, promising more effective and longer-lasting relief. Moreover, the trial explores both high and low doses of DNTH103 administered every two weeks, which could offer flexible options in managing dosage and minimizing side effects. This innovative approach could revolutionize how neuropathy is managed, offering new hope for patients seeking more sustainable solutions.

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

Research has shown that DNTH103 might help treat conditions like multifocal motor neuropathy (MMN). In a lab study using a model, DNTH103 improved the speed of nerve signal transmission, which is crucial for nerve health. Another study involving patients with a different nerve and muscle issue found that DNTH103 reduced tiredness by about 25% to 28%. These results suggest DNTH103 could enhance nerve and muscle function, potentially benefiting people with MMN. While these findings are promising, further research is necessary to confirm them. Participants in this trial will receive either a high dose or low dose of DNTH103, or a placebo, to further evaluate its effectiveness and safety. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-75 with a confirmed diagnosis of multifocal motor neuropathy (MMN) who respond to Ig treatment and are on a stable Ig regimen can join. They must weigh between 40-120 kg, have had the required vaccinations, and agree to contraception if they can have children. Women must not be able to become pregnant or use effective birth control; men must either be sterile or use contraception.

Inclusion Criteria

I am on a consistent treatment plan for my immune system.

I have signed the consent form for this study.

I am either not able to have children or will use effective birth control and not try to get pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DNTH103 or placebo every two weeks to evaluate safety, tolerability, pharmacometrics, and efficacy

17 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term to assess long-term safety and efficacy

Up to 52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DNTH103

Trial Overview The trial is testing DNTH103's safety, how well it's tolerated by patients, its pharmacometrics (how the drug moves through and affects the body), and effectiveness in treating MMN. Participants will randomly receive either DNTH103 or a placebo for comparison.

How Is the Trial Designed?

Group I: DNTH103 low dose Q2W Experimental Treatment 1 Intervention

Group II: DNTH103 high dose Q2W Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Dianthus Therapeutics

Lead Sponsor

Trials

3

Recruited

580+

Published Research Related to This Trial

Patients with axonal peripheral neuropathy caused by the nucleoside analogues didanosine (ddl), zalcitabine (ddC), and stavudine (d4T) showed significantly lower levels of acetyl-carnitine compared to control groups, suggesting a specific deficiency linked to neurotoxicity.

The study indicates that while mitochondrial DNA synthesis impairment is a primary cause of toxicity for these drugs, the deficiency in acetyl-carnitine may also play a critical role in the development of peripheral nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. Famularo, G., Moretti, S., Marcellini, S., et al.[2019]

Nerve growth factor (NGF) and insulin-like growth factors (IGF-I and IGF-II) show promise in treating diabetic peripheral neuropathy, with extensive testing in animal models yielding positive results.

Recombinant human nerve growth factor (rhNGF) has shown encouraging outcomes in phase II clinical trials for diabetic patients, and phase III trials have been completed, indicating progress towards potential new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotrophic factors in the therapy of diabetic neuropathy. Apfel, SC.[2019]

Diabetic neuropathy significantly impacts patients' quality of life and is linked to serious complications like foot ulcers and increased mortality, highlighting the need for effective drug treatments.

Randomized clinical trials (RCTs) evaluating treatments for diabetic neuropathy have historically been of poor quality, emphasizing the importance of well-designed studies that consider factors like neuropathy stage, outcome measures, and long-term effects to ensure meaningful results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials for drugs against diabetic neuropathy: can we combine scientific needs with clinical practicalities? Ziegler, D., Luft, D.[2019]

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]

Diabetic neuropathy (DN) affects about 50% of people with long-standing diabetes and is primarily caused by hyperglycemia, leading to nerve damage through mechanisms like sorbitol accumulation and protein glycation.

While polyneuropathy is generally considered irreversible, effective glycemic control and the use of aldose reductase inhibitors can stabilize or even reverse nerve damage, highlighting the importance of managing blood sugar levels in preventing DN progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diabetic neuropathy. Current concepts on etiopathogenesis, diagnosis, and treatment]. Zorrilla Hernández, E., Frati Munari, A., Lozano Castañeda, O., et al.[2009]

A family across four generations was identified with a hereditary neuropathy characterized primarily by debilitating neuropathic pain and sensory loss, with some motor dysfunction, indicating a significant impact on quality of life.

Genetic testing revealed a novel mutation (Trp101X) in the myelin protein zero gene, which is crucial for myelin structure, suggesting that this mutation contributes to the neuropathy's development and associated chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermediate Charcot-Marie-Tooth disease due to a novel Trp101Stop myelin protein zero mutation associated with debilitating neuropathic pain. Ramirez, JD., Barnes, PRJ., Mills, KR., et al.[2021]

The Overall Neuropathy Limitations Scale (ONLS) shows high inter-rater reliability and a strong correlation with established measures of disability and physical health, indicating it is a reliable tool for assessing peripheral neuropathy activities.

The ONLS demonstrates better content validity and less ceiling effect compared to the Overall Disability Sum Score (ODSS), making it potentially more effective for both clinical practice and research in evaluating neuropathy limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale. Graham, RC., Hughes, RA.[2022]

Recombinant human nerve growth factor (rhNGF) has been shown to be safe and well tolerated in healthy volunteers and patients with diabetic peripheral neuropathy (DPN), with doses up to 1.0 microg/kg administered intravenously or subcutaneously.

Preliminary phase II results indicate that rhNGF improves the function of small-fibre sensory peripheral neurons, supporting its potential as a treatment for DPN, with larger phase III trials currently underway to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human studies of recombinant human nerve growth factor and diabetic peripheral neuropathy. Freeman, R.[2017]

Recombinant human nerve growth factor (rhNGF) showed initial promise in phase II trials for treating diabetic polyneuropathy and HIV-related neuropathy, but a larger phase III trial with 1019 patients did not confirm these benefits, leading to the decision to halt further development.

The phase III trial revealed that painful side effects limited the dosage of rhNGF, and factors such as a strong placebo effect and changes in study populations may have contributed to the lack of efficacy observed in the larger trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nerve growth factor for the treatment of diabetic neuropathy: what went wrong, what went right, and what does the future hold? Apfel, SC.[2022]

In a phase I study involving 20 patients with AIDS or AIDS-related complex, the anti-retroviral drug dideoxycytidine was associated with the development of painful sensory and motor neuropathy in 9 out of 11 patients who were treated for more than 5 weeks, indicating a significant side effect of the drug.

The neuropathy typically began around 10 weeks of treatment and was characterized by sudden intense burning discomfort in the feet, suggesting that dideoxycytidine may act as an axonal toxin, particularly at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversible axonal neuropathy from the treatment of AIDS and related disorders with 2',3'-dideoxycytidine (ddC). Dubinsky, RM., Yarchoan, R., Dalakas, M., et al.[2016]

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 ... Claseprubart 300mg and 600mg demonstrated rapid, statistically significant and clinically meaningful improvements over placebo as measured by ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06537999

NCT06537999 | A Clinical Study to Evaluate DNTH103 in ... The purpose of this Phase 2 study is to evaluate the safety, tolerability, pharmacometrics, and efficacy of DNTH103 in participants with multifocal motor ...

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

FDA Clears Phase 2 MoMeNtum Trial of DNTH103 in ... In an established in vitro model of CIDP containing 10% human serum, DNTH103 showed the ability to restore neuronal conduction velocity, further ...

4. investor.dianthustx.com investor.dianthustx.com/news-releases/news-release-details/dianthus-therapeutics-highlights-recent-business-achievements-4

Release Details Dianthus is building a neuromuscular franchise with DNTH103 and anticipates reporting top-line data from the Phase 2 MaGic trial in generalized ...

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/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, ...