A Study to Evaluate the Efficacy and Safety of DNTH103 in Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CAPTIVATE)

Phase 3RecruitingNCT06858579

Dianthus Therapeutics256 enrolled

Overview

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

The study includes the following periods: * Part A: An open-label period (up to 13 weeks) * Part B: A randomized, placebo-controlled, double-blind treatment period (up to 52 weeks) for participants who respond to DNTH103 in Part A * Optional open-label extension (OLE) for eligible participants (up to 104 weeks) * Safety follow-up (40 weeks)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

256

Conditions

Chronic Inflammatory Demyelinating Polyneuropathy

Interventions

ClaseprubartDRUG

IV Infusion

ClaseprubartDRUG

SC injection

PlaceboDRUG

SC injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Must have given written informed consent before any study-related activities are carried out. 2. Weight range between 40 kilograms (kg) and 120 kg. 3. Confirmed diagnosis of CIDP or possible CIDP. Participants must have either typical CIDP or one of the following variants: motor or multifocal CIDP. Diagnosis must be confirmed by the Independent CIDP Review Panel. 4. CIDP Disease Activity Status (CDAS) score ≥ 3 at screening. 5. Must be neurologically stable. 6. Must have an INCAT score between 2 and 9 inclusive. 7. Must fulfill one of the following treatment conditions for CIDP: 1. Currently treated with and responded to immunoglobulin (Ig) (intravenous immunoglobulin \[IVIg\] or subcutaneous immunoglobulin \[SCIg\]) alone or Ig (IVIg or SCIg) plus oral corticosteroids, or previously treated with and responded to, but are no longer being treated with (eg, lost access to), a maintenance regimen of Ig (IVIg or SCIg) alone or Ig (IVIg or SCIg) plus oral corticosteroids. 2. Currently treated with and responded to oral corticosteroids alone or oral corticosteroids in combination with azathioprine or mycophenolate mofetil. 3. Refractory participants who have had treatment failure (worsening) or an inadequate response to Ig and/or oral corticosteroids (defined as no clinically meaningful improvement after a period of a minimum of 12 weeks, which may include both active treatment and observation to assess response), or who at any time were unable to tolerate these treatments, experienced adverse effects, or have documented contraindications. 4. Treatment naïve with no history of prior treatment for CIDP. 8. Documented vaccinations against encapsulated bacteria in accordance with local requirements and vaccine availability. 9. 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. 10. Male participants must 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 or be surgically sterile for at least 90 days prior to Screening. Exclusion Criteria: 1. Clinical signs or symptoms suggestive of polyneuropathy of causes other than CIDP. 2. Known evidence of central demyelination or known history of myelopathy. 3. History or presence of significant medical/surgical condition including any acute illness or major surgery considered to be clinically significant or that could have a potential impact on safety/efficacy or study procedures. 4. Any other condition, including mental illness or prior therapy that would make the participant unsuitable for this study. 5. Known complement deficiency or history of positive titer for anti-C1 antibodies. 6. Diagnosis of systemic lupus erythematosus (SLE) or family history of SLE (defined as a parent, sibling, or child). 7. Participants with an autoimmune disease affecting joints, muscle or nervous system. 8. Any coexisting or overlapping condition, which may interfere with outcome assessments, such as severe diabetic neuropathy, fibromyalgia, inflammatory arthritis or osteoarthritis affecting the hands and feet. 9. Prior history of N. meningitidis infection. 10. 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. 11. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies.

Locations (192)

Outcomes

Primary Outcomes

Part B: Time From First Dose to Relapse as Assessed by the Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT)

Adjusted INCAT scores range from 0-10 with a score of 10 indicating the greatest degree of disability. A relapse is defined as an increase of ≥1 point from baseline in adjusted INCAT score.

Time frame: Part B baseline to Part B end of treatment period (up to Week 52)

Secondary Outcomes

Part B: Time to Decrease of ≥ 4 Points (Centile Metric) in Inflammatory Rasch-built Overall Disability Scale (I-RODS) Score

The I-RODS score ranges from 0-100, with lower scores indicating the greatest degree of disability.

Time frame: Part B baseline to Part B end of treatment period (up to Week 52)

Part B: Time to Decrease of ≥ 8 kilopascal (kPa) in Grip Strength in the Dominant Hand

This is measured with a handheld device called a vigorimeter.

Time frame: Part B baseline to Part B end of treatment period (up to Week 52)

Part B: Percentage of Participants who Relapse as Assessed by the Adjusted INCAT

Adjusted INCAT scores range from 0-10 with a score of 10 indicating the greatest degree of disability. A relapse is defined as an increase of ≥1 point from baseline in adjusted INCAT score.

Time frame: Part B baseline to end of treatment period for Part B (up to Week 52)

Parts A and B: Change in I-RODS Score (Centile Metric)

The I-RODS score ranges from 0-100, with lower scores indicating the greatest degree of disability.

Time frame: Part A baseline up to Part A end of treatment period (up to Week 13); Part A baseline to Part B end of treatment period (up to Part B Week 52)

Parts A and B: Change in Grip Strength in the Dominant Hand

Central Contacts

Dianthus Clinical Contact Center

CONTACT

929-999-4055 clinicaltrials@dianthustx.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Clinical Study Site

Birmingham, Alabama, United States

RECRUITING

Clinical Study Site

Phoenix, Arizona, United States

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Clinical Study Site

Scottsdale, Arizona, United States

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Clinical Study Site

Los Angeles, California, United States

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Clinical Study Site

San Francisco, California, United States

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Clinical Study Site

San Francisco, California, United States

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Cinical Study Site

New Haven, Connecticut, United States

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Clinical Study Site

Washington D.C., District of Columbia, United States

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Clinical Study Site

Maitland, Florida, United States

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Clinical Study Site

Tampa, Florida, United States

RECRUITING

...and 182 more locations

This is measured with a handheld device called a vigorimeter.

Time frame: Part A baseline to Part A end of treatment period (up to Week 13); Part A baseline to Part B end of treatment period (up to Part B Week 52)

Parts A and B: Change in Adjusted INCAT Score

Adjusted INCAT scores range from 0-10 with a score of 10 indicating the greatest degree of disability.

Time frame: Part A baseline to Part A end of treatment period (up to Week 13); Part B baseline to Part B end of treatment period (up to Week 52); Part A baseline to Part B end of treatment period (up to Part B Week 52)

Parts A and B: Change in Grip Strength in the Nondominant Hand

This is measured with a handheld device called a vigorimeter.

Parts A and B: Change in Medical Research Council Sum Score (MRC-SS)

The MRC-SS ranges from 0 to 60 with a lower score indicating greater muscle weakness.

Part A: Percentage of Participants with a Confirmed Response to DNTH103 as Assessed by the Adjusted INCAT

Adjusted INCAT scores range from 0-10 with a score of 10 indicating the greatest degree of disability. A response is defined as a decrease of ≥1 point from baseline in adjusted INCAT score.

Time frame: Part A baseline to Part A end of treatment period (up to Week 13)

Parts A and B: Change in Euro-Quality of Life Visual Analogue Scale (EQ-VAS)

Participants mark their health status from 0 to 100 with 100 indicating the best health state.

Parts A and B: Change in Fatigue Severity Scale (FSS)

FSS assesses disabling fatigue in participants with chronic illness.

Parts A and B and OLE: Change in Adjusted INCAT Score

Adjusted INCAT scores range from 0-10 with a score of 10 indicating the greatest degree of disability.

Time frame: Part A baseline to OLE Week 52 and Week 104; Part B baseline to OLE Week 52 and Week 104; OLE baseline to OLE Week 52 and Week 104

Part B and OLE: Percentage of Participants With a Confirmed Relapse as Assessed by the Adjusted INCAT

Adjusted INCAT scores range from 0-10 with a score of 10 indicating the greatest degree of disability. A relapse is defined as an increase of ≥1 point from baseline in adjusted INCAT score.

Time frame: Part B baseline to OLE Week 52 and Week 104; OLE baseline to OLE Week 52 and Week 104

Parts A, B, OLE, and Safety Follow-up: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)

An adverse event (AE) is any undesirable experience associated with the use of a medicine, which does not necessarily have a causal relationship with the medicine. A TEAE is an AE with onset after the start of the medicine, or any worsening of a pre-existing medical condition/AE after the start of the medicine. An SAE is an AE that can cause disability, is life-threatening, results in hospitalization or death, or is a birth defect.

Time frame: Part A baseline through Safety Follow-up period (up to approximately 209 weeks)

Parts A, B, OLE, and Safety Follow-up: Serum Concentrations of DNTH103

Blood samples will be collected for measurement of serum concentrations of DNTH103 at various timepoints both pre- and post-dose.

Time frame: Part A baseline through Safety Follow-up period (up to approximately 209 weeks)

Parts A, B, and OLE: Change from Baseline in Complement Total Blood Test (CH50)

Blood samples will be collected to determine changes in CH50 at various timepoints.

Time frame: Part A baseline through Safety Follow-up period (up to approximately 209 weeks)

Parts A, B, OLE, and Safety Follow-up: Incidence and Titer of Antidrug Antibodies (ADAs)

Blood samples will be collected to measure ADA against DNTH103 at various timepoints.

Time frame: Part A baseline through Safety Follow-up period (up to approximately 209 weeks)