Clinical trial NCT06858579: A Study to Evaluate the Efficacy and Safety of DNTH103 in Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CAPTIVATE)
Official title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of DNTH103 In Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CAPTIVATE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Inflammatory Demyelinating Polyneuropathy
Lead sponsor: Dianthus Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-03-05
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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)

Eligibility criteria: 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 (ie, no relapses or other neurological events that could affect examinations).
6. Must have an adjusted 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 either no longer have access to or are no longer being treated with, 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, or previously treated with and responded to, but no longer have access to, oral corticosteroids.
   3. Refractory participants who have had failure (worsened) or an inadequate response (defined as no clinically meaningful improvement after treatment for a minimum of 12 weeks on Ig and/or oral corticosteroids) or are unable to tolerate these treatments due to side effects.
   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 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. Clinical signs or symptoms suggestive of polyneuropathy of other causes, such as inflammatory neuropathies.
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. Diagnosis of an autoimmune disorder other than CIDP.
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.

Primary outcomes:
measure: Part B: Time From First Dose to Relapse as Assessed by the Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT)
timeFrame: Part B baseline to Part B end of treatment period (up to Week 52)
Secondary outcomes:
measure: Part B: Percentage of Participants who Relapse as Assessed by the Adjusted INCAT
timeFrame: Part B baseline to end of treatment period for Part B (up to Week 52)
measure: Part B: Change in Inflammatory Rasch-built Overall Disability Scale (I-RODS) Score
timeFrame: Part B baseline to Part B end of treatment period (up to Week 52)
measure: Part B: Change in Grip Strength in the Dominant Hand
timeFrame: Part B baseline to Part B end of treatment period (up to Week 52)
measure: Parts A and B: Change in I-RODS Score
timeFrame: 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)
measure: Parts A and B: Change in Grip Strength in the Dominant Hand
timeFrame: 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)
measure: Parts A and B: Change in Adjusted INCAT Score
timeFrame: 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)
measure: Parts A and B: Change in Grip Strength in the Nondominant Hand
timeFrame: 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)
measure: Parts A and B: Change in Medical Research Council Sum Score (MRC-SS)
timeFrame: 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)
measure: Part A: Percentage of Participants with a Confirmed Response to DNTH103 as Assessed by the Adjusted INCAT
timeFrame: Part A baseline to Part A end of treatment period (up to Week 13)
measure: Parts A and B: Change in Euro-Quality of Life Visual Analogue Scale (EQ-VAS)
timeFrame: 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)
measure: Parts A and B: Change in Fatigue Severity Scale (FSS)
timeFrame: 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)
measure: Parts A and B and OLE: Change in Adjusted INCAT Score
timeFrame: 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
measure: Part B and OLE: Percentage of Participants With a Confirmed Relapse as Assessed by the Adjusted INCAT
timeFrame: Part B baseline to OLE Week 52 and Week 104; OLE baseline to OLE Week 52 and Week 104
measure: Parts A, B, OLE, and Safety Follow-up: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Part A baseline through Safety Follow-up period (up to approximately 209 weeks)
measure: Parts A, B, OLE, and Safety Follow-up: Serum Concentrations of DNTH103
timeFrame: Part A baseline through Safety Follow-up period (up to approximately 209 weeks)
measure: Parts A, B, and OLE: Change from Baseline in Complement Total Blood Test (CH50)
timeFrame: Part A baseline through Safety Follow-up period (up to approximately 209 weeks)
measure: Parts A, B, OLE, and Safety Follow-up: Incidence and Titer of Antidrug Antibodies (ADAs)
timeFrame: Part A baseline through Safety Follow-up period (up to approximately 209 weeks)
Other outcomes:
Locations:
city: Maitland
country: United States
facility: Clinical Study Site
state: Florida
city: Honolulu
country: United States
facility: Clinical Study Site
state: Hawaii
city: Edwardsville
country: United States
facility: Clinical Study Site
state: Illinois
city: Indianapolis
country: United States
facility: Clinical Study Site
state: Indiana
city: New York
country: United States
facility: Clinical Study Site
state: New York
city: Cincinnati
country: United States
facility: Clinical Study Site
state: Ohio
city: Dallas
country: United States
facility: Clinical Study Site
state: Texas
city: Denton
country: United States
facility: Clinical Study Site
state: Texas
city: Houston
country: United States
facility: Texas Locations
state: Texas
city: Sugar Land
country: United States
facility: Clinical Study Site
state: Texas
Study officials:
References: