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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dianthus Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

4 Aug 2025 → ongoing

Decision date (initial)

2025-06-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Dianthus Therapeutics Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate the efficacy of DNTH103 compared to placebo based on the time to relapse.

Secondary objectives 8

1. To demonstrate the efficacy of DNTH103 compared to placebo based on time to a decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS) disability scores during Part B
2. To demonstrate the efficacy of DNTH103 compared to placebo based on time to a decrease in grip strength in the dominant hand during Part B
3. To assess the efficacy of DNTH103 in Part A and Part B based on measures of muscle strength and disability
4. To assess the efficacy of DNTH103 based on health-related quality of life outcomes
5. To assess the long-term efficacy and durability of response of DNTH103 during the open-label extension (OLE)
6. To assess the safety and tolerability of DNTH103
7. To assess the pharmacokinetics (PK) and pharmacodynamics (PD) of DNTH103
8. To assess the immunogenicity of DNTH103

Conditions and MedDRA coding

Chronic Inflammatory Demyelinating Polyneuropathy

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Paul-Ehrlich-Institut, Danish Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 fulfil one of the following treatment conditions for CIDP: a. 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. b.Currently treated with and responded to oral corticosteroids alone or oral corticosteroids in combination with azathioprine or mycophenolate mofetil. c. 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, due to side, experienced adverse effects, or have documented contraindications. d. 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 11

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Part B: Time from first dose to relapse as assessed by the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT)

Secondary endpoints 17

1. Part B: Time to decrease of ≥ 4 points (centile metric) in Inflammatory Rasch-built Overall Disability Scale (I-RODS) score
2. Part B: Time to a decrease of ≥ 8 kilopascal (kPa) in grip strength in the dominant hand
3. Part B: Proportion of participants who relapse as assessed by the adjusted INCAT
4. Parts A and B: Change in I-RODS score
5. Parts A and B: Change in grip strength in the dominant hand
6. Parts A and B: Change in adjusted INCAT Score
7. Parts A and B: Change in grip strength in the nondominant hand
8. Parts A and B: Change in Medical Research Council Sum Score (MRC-SS)
9. Part A: Proportion of participants with a confirmed response to DNTH103 as assessed by the adjusted INCAT
10. Parts A and B: Change in Euro-Quality of Life Visual Analogue Scale (EQ-VAS)
11. Parts A and B: Change in Fatigue Severity Scale (FSS)
12. Parts A and B and OLE: Change in adjusted INCAT score
13. Part B and OLE: Proportion of participants with a confirmed relapse as assessed by the adjusted INCAT
14. Parts A, B, OLE, and Safety Follow-up: Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)
15. Parts A, B, OLE, and Safety Follow-up: Serum concentrations of DNTH103
16. Parts A, B, and OLE: Change from baseline in complement total blood test (CH50)
17. Parts A, B, OLE, and Safety Follow-up: Incidence and titer of antidrug antibodies (ADAs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dianthus Therapeutics Inc.

Sponsor organisation

Dianthus Therapeutics Inc.

Address

7 Times Square Floor 43rd Suite 4303

City

New York

Postcode

10036-6508

Country

United States

Scientific contact point

Organisation

Dianthus Therapeutics Inc.

Contact name

Scientific CTIS contact point

Public contact point

Organisation

Dianthus Therapeutics Inc.

Contact name

Public CTIS contact point

Third parties 9

Locations

12 EU/EEA countries · 72 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 173 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications