Adults with chronic inflammatory demyelinating polyneuropathy
Conditions
Interventions
DNTH103 300 mg:DNTH103 300 mg
placebo:placebo
DNTH103 600 mg:DNTH103 600 mg
Sponsors
Huashan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects. 2. Adult males and females = 18-75 years of age (inclusive) at Screening. 3. Weight range between 40 kg and 120 kg at Screening. 4. A diagnosis of CIDP or possible CIDP per the 2021 EAN/PNS guidelines. Participants must have either typical CIDP or one of the following variants: motor or multifocal CIDP. Diagnosis must be confirmed by the ICRP, which may determine that a participant requires additional standard-of-care procedures (eg, nerve conduction studies and imaging studies) to inform their assessment. 5. CIDP Disease Activity Status (CDAS) score = 3 at Screening. 6. Must be neurologically stable (ie, no relapses or other neurological events that could affect examinations) at Screening and confirmed prior to dosing on Day 1 of Part A. The participant must be stabilized at least 1 week prior to Day 1 of Part A. Clinically meaningful deterioration may occur during Screening (eg, during corticosteroid tapering) and is defined as at least one of the following: (1) = 1-point increase in adjusted INCAT score (2) = 4 points decrease in I-RODS total score (3) = 3 points decrease in MRC-SS (4) = 8 kilopascal worsening in mean grip strength (one hand) or (5) a significant deterioration in the participant’s health per the Investigator’s judgment; 7. Must have an adjusted INCAT score between 2 and 9 inclusive at Screening and confirmed on Day 1 of Part A prior to dosing. Participants with an adjusted INCAT score of 2 at study entry must have this score exclusively from the leg disability subscore. 8. Must fulfill one of the following treatment conditions for CIDP: (1) Currently treated with and responded to Ig (IVIg or 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. Clinically meaningful improvement is defined as one of the following: 1) = 1-point decrease in adjusted INCAT score, 2) = 4 points increase in I-RODS total score, 3) = 3 points increase in MRC-SS, 4) = 8 kilopascal improvement in mean grip strength (one hand), or 5) an equivalent improvement based on information documented in medical records and per the Investigator's judgment. (4) Treatment naïve with no history of prior treatment for CIDP. 9. Participants on Ig, corticosteroids, or immunosuppressant drugs must adhere to the following stability requirements: (1) If currently treated with Ig, must have received a stable maintenance dose for at least 3 cycles or 6 weeks, whichever is longer, prior to Screening and then remain on the same stable maintenance dose until enrollment on Day 1 of Part A with the typical IV maintenance dosing of 0.4-1.0 g/kg e
Exclusion criteria
Exclusion criteria: 1. Clinical signs or symptoms suggestive of polyneuropathy of other causes, such as inflammatory neuropathies. 2. Any other neurologic or other disease that could better explain the participant’s signs and symptoms or that could cause signs/symptoms that could interfere with treatment or outcome assessments. 3. Diagnosis with CIDP variants not specified above per the 2021 EAN/PNS guidelines. 4. Known evidence of central demyelination or known history of myelopathy; 5. 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 in the opinion of the Investigator. A planned surgery during the treatment period may be allowed in consultation with the Medical Monitor. 6. Any other condition, including mental illness or prior therapy that in the opinion of the Investigator would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements. 7. Known complement deficiency or history of positive titer for anti-C1 antibodies. 8. Diagnosis of SLE or family history of SLE (defined as a parent, sibling, or child). 9. Diagnosis of an autoimmune disorder other than CIDP. Exceptions (other than SLE) may be allowed following consultation with the Medical Monitor and based on the Investigator’s clinical judgment. 10. 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 (among others). 11. Prior history (at any time) of N. meningitidis infection. 12. 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. 13. History of hospitalization for 24 hours or longer within the 6 weeks (42 days) prior to Part A Day 1 unless discussed with the Medical Monitor. 14. Poorly controlled diabetes (hemoglobin A1c [HbA1c] > 7%); 15. Clinically significant drug or alcohol abuse in the opinion of the Investigator. 16. Known hypersensitivity to any of the study treatment ingredients or other therapeutic proteins. 17. Females who are breastfeeding or planning to breastfeed at any time during the study. 18. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies during Screening. Participants who have no evidence of cirrhosis, have completed a curative intent regimen for HCV, and are deemed by a gastroenterologist to have no active HCV will not be excluded. 19. Liver test results elevated more than 2-fold above the ULN for GGT, bilirubin (total), AST, or ALT. 20. For female participants of childbearing potential, a positive serum pregnancy test during Screening or a positive urine pregnancy test (with confirmatory serum pregnancy test) on Part A Day 1. 21. An ANA titer = 1:320, or positive for both ANA (any titer) and dsDNA, at Screening. If participants have these laboratory values after recent Ig treatment, they may be retested following discussion and agreement between the Investi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time from first dose in Part B to relapse as assessed by the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) during Part B; | — |
Secondary
| Measure | Time frame |
|---|---|
| Serum concentrations and PK parameters of DNTH103;Change in neurofilament light chain (NfL) levels in serum and plasma ;Due to word limit, please refer to Chinese;Proportion of participants who relapse as assessed by the adjusted INCAT during Part B;Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent SAEs (Part A, Part B, OLE, and Safety Follow-up);Incidence and titer of antidrug antibodies (ADAs);Serum concentrations and PK parameters of DNTH103,;Change in I-RODS score from Part B baseline to Part B end-of-treatment period (EOTP);Advantageous grip strength;Change in adjusted INCAT score:Proportion of participants with a confirmed relapse as assessed by the adjusted INCAT;Change in grip strength in the dominant hand from Part B baseline to Part B EOTP;Change in Euro-Quality of Life Visual Analogue Scale (EQ-VAS) ;Change in Euro-Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) scale ; | — |
Countries
China
Contacts
Public ContactJie Lin
Huashan Hospital, Fudan University
Outcome results
None listed