DNTH103 for Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

Inclusion criteria

• {"criterion_text":"- Must have given written informed consent before any study-related activities are carried out."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Weight range between 40 kilograms (kg) and 120 kg."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- CIDP Disease Activity Status (CDAS) score ≥ 3 at screening."}
• {"criterion_text":"- Must be neurologically stable"}
• {"criterion_text":"- Must have an INCAT score between 2 and 9 inclusive."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Documented vaccinations against encapsulated bacteria in accordance with local requirements and vaccine availability."}
• {"criterion_text":"- 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"}

Exclusion criteria

• {"criterion_text":"- Clinical signs or symptoms suggestive of polyneuropathy of causes other than CIDP."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies."}
• {"criterion_text":"- Known evidence of central demyelination or known history of myelopathy."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Any other condition, including mental illness or prior therapy that would make the participant unsuitable for this study."}
• {"criterion_text":"- Known complement deficiency or history of positive titer for anti-C1 antibodies."}
• {"criterion_text":"- Diagnosis of systemic lupus erythematosus (SLE) or family history of SLE (defined as a parent, sibling, or child)."}
• {"criterion_text":"- Participants with an autoimmune disease affecting joints, muscle or nervous system."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Prior history of N. meningitidis infection."}

Primary endpoints

• {"endpoint_text":"- Part B: Time from first dose to relapse as assessed by the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT)","definition_or_measurement_approach":"Time-to-event: time from first dose to relapse assessed by the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) score."}

Secondary endpoints

• {"endpoint_text":"- Part B: Time to decrease of ≥ 4 points (centile metric) in Inflammatory Rasch-built Overall Disability Scale (I-RODS) score","definition_or_measurement_approach":"Time-to-event: time until ≥4-point decrease in I-RODS (centile metric)."}
• {"endpoint_text":"- Part B: Time to a decrease of ≥ 8 kilopascal (kPa) in grip strength in the dominant hand","definition_or_measurement_approach":"Time-to-event: time until ≥8 kPa decrease in dominant hand grip strength."}
• {"endpoint_text":"- Part B: Proportion of participants who relapse as assessed by the adjusted INCAT","definition_or_measurement_approach":"Proportion (%) of participants meeting relapse criteria per adjusted INCAT during Part B."}
• {"endpoint_text":"- Parts A and B: Change in I-RODS score","definition_or_measurement_approach":"Change from baseline in I-RODS score measured in Parts A and B."}
• {"endpoint_text":"- Parts A and B: Change in grip strength in the dominant hand","definition_or_measurement_approach":"Change from baseline in dominant-hand grip strength measured in Parts A and B."}
• {"endpoint_text":"- Parts A and B: Change in adjusted INCAT Score","definition_or_measurement_approach":"Change from baseline in adjusted INCAT score measured in Parts A and B."}
• {"endpoint_text":"- Parts A and B: Change in grip strength in the nondominant hand","definition_or_measurement_approach":"Change from baseline in nondominant-hand grip strength measured in Parts A and B."}
• {"endpoint_text":"- Parts A and B: Change in Medical Research Council Sum Score (MRC-SS)","definition_or_measurement_approach":"Change from baseline in MRC Sum Score measured in Parts A and B."}
• {"endpoint_text":"- Part A: Proportion of participants with a confirmed response to DNTH103 as assessed by the adjusted INCAT","definition_or_measurement_approach":"Proportion (%) of participants in Part A with confirmed response per adjusted INCAT."}
• {"endpoint_text":"- Parts A and B: Change in Euro-Quality of Life Visual Analogue Scale (EQ-VAS)","definition_or_measurement_approach":"Change from baseline in EQ-VAS measured in Parts A and B."}
• {"endpoint_text":"- Parts A and B: Change in Fatigue Severity Scale (FSS)","definition_or_measurement_approach":"Change from baseline in Fatigue Severity Scale measured in Parts A and B."}
• {"endpoint_text":"- Parts A and B and OLE: Change in adjusted INCAT score","definition_or_measurement_approach":"Change from baseline in adjusted INCAT score measured across Parts A, B and open-label extension (OLE)."}
• {"endpoint_text":"- Part B and OLE: Proportion of participants with a confirmed relapse as assessed by the adjusted INCAT","definition_or_measurement_approach":"Proportion (%) of participants with confirmed relapse per adjusted INCAT in Part B and OLE."}
• {"endpoint_text":"- Parts A, B, OLE, and Safety Follow-up: Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs)","definition_or_measurement_approach":"Incidence and nature of TEAEs and treatment-emergent SAEs collected across Parts A, B, OLE and safety follow-up."}
• {"endpoint_text":"- Parts A, B, OLE, and Safety Follow-up: Serum concentrations of DNTH103","definition_or_measurement_approach":"Serum concentration (PK) measurements of DNTH103 at scheduled timepoints across Parts A, B, OLE and safety follow-up."}
• {"endpoint_text":"- Parts A, B, and OLE: Change from baseline in complement total blood test (CH50)","definition_or_measurement_approach":"Change from baseline in CH50 complement activity measured across Parts A, B and OLE."}
• {"endpoint_text":"- Parts A, B, OLE, and Safety Follow-up: Incidence and titer of antidrug antibodies (ADAs)","definition_or_measurement_approach":"Incidence and titers of ADAs measured at scheduled timepoints across Parts A, B, OLE and safety follow-up."}

Methods

• Patient brochure (country-specific) — patient-facing brochure documents (K2_Patient Brochure) available for multiple MSCs/countries.
• Patient flyer (country-specific) — short flyer materials (K2_Patient Flyer) for multiple MSCs/countries.
• Website posting (country-specific) — trial website postings and recruitment web notices for multiple MSCs/languages (K2_Website Posting / Website Posting files).
• Recruitment arrangements documents (K1) — formal recruitment procedure documents per country (K1_Recruitment procedure/arrangements files).
• Foundation / advocacy website postings — e.g., CIDP Foundation / local foundation website postings (document titles reference Foundation Website Posting and BS CIDP Foundation Website Posting).

Primary sponsor

Full Name

Dianthus Therapeutics Inc.

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

United States

Contract research organisations

Name

Worldwide Clinical Trials d.o.o.

Responsibilities

Multiple sponsor duties indicated (codes: 1,11,12,13,14,2,5,6,8) as listed in CTIS third-party entries.

Third parties

• {"country":"Croatia","full_name":"Worldwide Clinical Trials d.o.o.","duties_or_roles":"[\"1\",\"11\",\"12\",\"13\",\"14\",\"2\",\"5\",\"6\",\"8\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Merative US LP","duties_or_roles":"[\"7\"]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"[\"14\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Labor Dr. Wisplinghoff GbR","duties_or_roles":"[\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"China","full_name":"Wuxi Biologics Co. Ltd.","duties_or_roles":"[\"14\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Accurant Biotech Inc.","duties_or_roles":"[\"15\",\"4\"] (note: includes 'blood samples storage' per entry)","organisation_type":"Industry"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"[\"3\"]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Kcas LLC","duties_or_roles":"[\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"LabConnect GmbH","duties_or_roles":"[\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}