DNTH103 for Neuropathy

(MOMENTUM Trial)

Recruiting at 7 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

Trial Summary

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.

What data supports the effectiveness of the drug DNTH103 for neuropathy?

Research on similar treatments, like nerve growth factor (NGF), shows that they can improve nerve function in conditions like diabetic neuropathy, although some studies had mixed results. NGF has been tested in clinical trials and showed promise in early phases, but later trials did not confirm its effectiveness, possibly due to issues like dosage and placebo effects. ^{1 2 3 4 5}

How is the drug DNTH103 different from other treatments for neuropathy?

DNTH103 is unique because it may target specific genetic mutations associated with neuropathic pain, unlike other treatments that focus on general symptom management or metabolic control. This approach could potentially address the underlying cause of neuropathy in certain hereditary cases. ^{6 7 8 9 10}

What is the purpose of this trial?

The purpose of this Phase 2 study is to evaluate the safety, tolerability, pharmacometrics, and efficacy of DNTH103 in participants with multifocal motor neuropathy (MMN).

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

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

2. United States 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? [2022]

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

A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale. [2022]

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Intermediate Charcot-Marie-Tooth disease due to a novel Trp101Stop myelin protein zero mutation associated with debilitating neuropathic pain. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. [2019]

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

Reversible axonal neuropathy from the treatment of AIDS and related disorders with 2',3'-dideoxycytidine (ddC). [2016]

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

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

10. Mexico pubmed.ncbi.nlm.nih.gov

[Diabetic neuropathy. Current concepts on etiopathogenesis, diagnosis, and treatment]. [2009]