Multifocal Motor Neuropathy
Conditions
Brief summary
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).
Interventions
DRUGDNTH103
* Day 1: IV loading dose * Week 1 to Week 15: DNTH103 administered SC every 2 weeks
DRUGPlacebo
* Day 1: IV infusion of placebo * Week 1 to Week 15: placebo administered SC every 2 weeks
Sponsors
Dianthus Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Must have given written informed consent before any study-related activities are carried out 2. Adult males and females, 18 to 75 years of age (inclusive). 3. Weight range between 40 to 120 kilograms (kg). 4. Confirmed diagnosis of definite or probable MMN. 5. Evidence of: 1. Responsiveness to Ig treatment; and 2. Receiving a stable Ig regimen 6. Documented vaccinations against encapsulated bacteria in accordance with local requirements and vaccine availability. 7. Female participants must be of nonchildbearing potential or if of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use a highly effective method of contraception. 8. Male participants must be surgically sterile for at least 90 days prior to Screening or agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception.
Exclusion criteria
1. History or presence of significant medical/surgical condition including any acute illness or major surgery considered to be clinically significant or that could impact efficacy assessments. 2. Any coexisting conditions which may interfere with outcome assessments (eg, severe diabetic neuropathy). 3. Concurrent or previous use of rituximab, cyclophosphamide, mycophenolate mofetil, azathioprine, or cyclosporine. If a participant has previously used these medications, the last dose must be at least 6 months prior to randomization. 4. Currently or previously on complement inhibitors including in a clinical trial setting. 5. Prior history (at any time) of N. meningitidis infection. 6. Diagnosis of an autoimmune disorder other than MMN. 7. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies during Screening. 8. History of active malignancy within 5 years prior to Screening, except basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, cervical carcinoma in situ curatively treated or low-grade prostate adenocarcinoma for which appropriate management is observation alone. 9. Participation in another clinical study of an investigational drug within 90 days or 5 half-lives of the investigational agent (whichever is longer) prior to randomization (Day 1). 10. Any other overlapping condition for which the condition or treatment of the condition may affect the study assessments or outcomes. 11. Any other condition, including mental illness or prior therapy, that in the opinion of the Investigator would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Baseline to Week 17 | Incidence of treatment-emergent adverse events (TEAEs) and treatment emergent serious adverse events (SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Clinical Deterioration (CD) | Baseline to Week 17 | The time it takes a participant to meet defined criteria for worsening of symptoms in the study |
| Mean Value, Mean Change, and Percentage Change From Baseline in Grip Strength | Baseline to Week 17 | Grip strength measured in kilopascal (kPa) using a vigorimeter |
| Area Under Curve (AUC) of the Change From Baseline in Grip Strength | Baseline to Week 17 | Grip strength measured in kPa using a vigorimeter |
| AUC of the Change From Baseline in Medical Research Council (MRC)-10 Sum Score | Baseline to Week 17 | MRC-10 evaluates motor strength/weakness from a predetermined set of 10 muscle pairs (upper and lower limbs) on a scale of 0 to 5 |
| Mean Value and Mean Change From Baseline in MRC-10 Sum Score | Baseline to Week 17 | MRC-10 evaluates motor strength/weakness from a predetermined set of 10 muscle pairs (upper and lower limbs) on a scale of 0 to 5 |
| Mean Value and Mean Change From Baseline in MRC-14 Sum Score | Baseline to Week 17 | MRC-14 evaluates motor strength/weakness from a predetermined set of 14 muscle pairs (upper and lower limbs) on a scale of 0 to 5 |
| Mean Value and Mean Change From Baseline in Multifocal Motor Neuropathy Rasch-Built Overall Disability Scale (MMN-RODS) Score | Baseline to Week 17 | MMN-RODS consists of 25 items scored on a 3-point scale |
| Mean Value and Mean Change From Baseline in Average Time to Complete the 9-Hole Peg Test (9-HPT) | Baseline to Week 17 | 9-HPT is a quantitative measure of upper extremity (arm and hand) function and dexterity |
| Mean Change From Baseline in Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | Baseline to Week 17 | INCAT comprises 2 parts, the arm score and the leg score. Each part is scored between 0 and 5 points, resulting in an INCAT total score between 0 and 10. Adjusted INCAT disability score excludes changes in upper limb function from 0 (normal) to 1 (minor symptoms) |
| Time to Retreatment With Immunoglobulin (Ig) Since the Final Ig Treatment Before Randomization | Baseline to Week 17 | Time between the participant's last dose of Ig and when they require the next dose of Ig after entering the randomized, controlled treatment period of the study |
| Mean Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) | Baseline to Week 17 | A vertical VAS is included in the EQ 5D 5L. Participants mark their health status from 0 to 100 |
| Count and Proportion of Participants With Patient Global Impression of Change (PGIC) Score of Improved or Better | Baseline to Week 17 | PGIC is a 7-point scale depicting a participant's rating of overall improvement |
| Mean Change From Baseline in Fatigue Severity Scale (FSS) Score | Baseline to Week 17 | FSS assesses disabling fatigue in participants with chronic illness |
| Mean Change From Baseline in Health-Related Productivity Questionnaire (HRPQ) Outcomes | Baseline to Week 17 | HRPQ is a participant diary tool designed to provide data on health-related impacts to labor force participation |
| Effectiveness, Side Effects, Convenience, and Overall Satisfaction Scores as Assessed by Treatment Satisfaction Questionnaire for Medications (TSQM)-14 | Baseline to Week 17 | TSQM-14 is a 14-item treatment satisfaction questionnaire that evaluates the following domains: effectiveness, side effects, convenience, and global satisfaction |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | Up to Week 52 of OLE | Incidence of treatment-emergent adverse events (TEAEs) and treatment emergent serious adverse events (SAEs) |
| Serum Concentrations of DNTH103 | Baseline to Week 17 | Blood samples will be collected for measurement of serum concentrations of DNTH103 at various timepoints both pre- and post-dose |
| Incidence and Titer of Antidrug Antibody (ADA) Levels Against DNTH103 | Baseline to Week 17 | Blood samples will be collected to measure ADA against DNTH103 at various timepoints |
| Mean Change From Baseline in Euro-Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) Scale | Baseline to Week 17 | EQ-5D-5L is comprised of 5 dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression |
Countries
Denmark, France, Italy, Netherlands, North Macedonia, Poland, Serbia, Spain, United Kingdom, United States
Contacts
Primary ContactDianthus Clinical Contact Center
Outcome results
None listed