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)

Summary:

This study is a global, multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial evaluating the safety and efficacy of DNTH103, an investigational therapy, in adult patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Approximately 480 participants will be enrolled worldwide across leading academic medical centers, including Hospital for Special Surgery (HSS).

The study consists of multiple parts:

• Part A: An open-label treatment period of up to 13 weeks to evaluate initial response to DNTH103. Participants will receive subcutaneous DNTH103 every two weeks, following an initial intravenous loading dose.
• Part B: Eligible responders from Part A will be randomized to receive either DNTH103 or placebo every two weeks in a double-blind phase lasting up to 52 weeks.
• Optional Open-Label Extension: Participants completing the double-blind phase or experiencing a relapse may enter an open-label extension for up to 104 weeks.
• Follow-Up: A 40-week safety follow-up period after treatment completion.

Enrollment Period: Participant enrollment is expected to continue on a rolling basis through 2025.

Follow-Up Duration: Total study participation, including treatment and safety follow-up, may last up to four years per participant.

Inclusion Criteria:

1. Must have given written informed consent before any study-related activities are carried out.
2. Adult males and females ≥ 18-75 years of age (inclusive) at Screening.
3. Weight range between 40 kilograms (kg) and 120 kg.
4. 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.
5. CIDP Disease Activity Status (CDAS) score ≥ 3 at screening.
6. Must be neurologically stable (i.e., no relapses or other neurological events that could affect examinations).
7. Must have an adjusted INCAT score between 2 and 9 inclusive.
8. 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.
9. Documented vaccinations against encapsulated bacteria in accordance with local requirements and vaccine availability.
10. 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.
11. 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.

Contact Information for the study (Full Name, email address, phone number):

Kathleen Peterson

neurologyresearch@hss.edu

917.260.4904