DNTH103 for Generalized Myasthenia Gravis

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Participants must be receiving at least 1 but not more than 3 of the following immunosuppressant medications at Screening, provided they have a stable daily dose for the minimum periods outlined below and maintain throughout the study: a. If taking oral corticosteroids, must have been taking for at least 4 weeks (28 days) prior to randomization, with doses not to exceed an average of 40 mg/day (280 mg/week) of prednisone or its equivalent; b. If taking azathioprine, must have been taking for at least 6 months (180 days) at time of randomization with a stable dose for at least 2 months (60 days) prior to randomization; c. If taking other immunosuppressants, must have been on other immunosuppressants (such as cyclosporin, mycophenolate mofetil, cyclophosphamide, or methotrexate) for at least 3 months (90 days) at time of randomization with a stable dose for at least 1 month (30 days) prior to randomization."}
• {"criterion_text":"- Female participants must: a. Be of nonchildbearing potential, ie, surgically sterilized via laparoscopic methods at least 6 weeks before Screening, if surgically sterilized via open abdominal surgery, at least 12 weeks before Screening or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone [FSH] level ≥ 40 IU/L at Screening), or b. 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 from signing the informed consent form throughout the study until the end of the Safety Follow-up period, or longer if required in accordance with local requirements."}
• {"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 from signing the informed consent form throughout the study until the end of the Safety Follow-up period, or longer if required in accordance with local requirements."}
• {"criterion_text":"- No clinically significant abnormalities (in the opinion of the Investigator) during Screening, including: a. No clinically significant findings in serum chemistry, hematology, coagulation, and urinalysis tests. b. Triplicate 12-lead electrocardiogram (ECG) with a mean QT interval corrected using the Fridericia method (QTcF) ≤ 450 msec for males and ≤ 460 msec for females and no clinically significant abnormalities. The triplicate 12-lead ECG assessment may be repeated once, if abnormal values were recorded in any of the 3 readings completed in the first instance, at the discretion of the PI. Electrocardiogram findings outside of normal ranges may be considered acceptable if determined by the Investigator to be not clinically significant."}
• {"criterion_text":"- Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions."}
• {"criterion_text":"- Adult males and females, 18 to 75 years of age (inclusive) at Screening."}
• {"criterion_text":"- Weight range between 40-120 kg at Screening."}
• {"criterion_text":"- Diagnosed with gMG at least 3 months (90 days) before the Screening visit, confirmed as specified in inclusion criterion #5 below."}
• {"criterion_text":"- Diagnosis of gMG by the following tests: a. Acetylcholine receptor antibody (AChR Ab) positive as confirmed during the Screening period prior to randomization, and b. One of the following: i. History of abnormal neuromuscular transmission test, consistent with gMG, as demonstrated by single-fiber electromyography or repetitive nerve stimulation; ii. History of positive anticholinesterase test (eg, edrophonium); iii. Clinical response to acetylcholinesterase inhibitors such as pyridostigmine (Mestinon®) as assessed by the treating physician."}
• {"criterion_text":"- Myasthenia Gravis Foundation of America (MGFA) Class II-IVa, at Screening and confirmed at randomization."}
• {"criterion_text":"- Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 6 or more, at Screening and confirmed at randomization."}
• {"criterion_text":"- Participants must have documented vaccinations against encapsulated bacterial pathogens N. meningitidis (including serogroup B meningococcus, where available) and S. pneumoniae within 3 years of enrollment or be vaccinated at least 2 weeks (14 days) prior to randomization. They should also have documented vaccinations against H. influenzae within 3 years prior to enrollment or be vaccinated at least 2 weeks (14 days) prior to randomization in accordance with local requirements and based on vaccine availability."}
• {"criterion_text":"- Participants using acetylcholinesterase inhibitors (eg, pyridostigmine, Mestinon) at Screening are allowed to continue provided they maintain a stable daily dose for a minimum period of 2 weeks (14 days) prior to randomization."}

Exclusion criteria

• {"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 potential impact on safety/efficacy or study procedures in the opinion of the Investigator."}
• {"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":"- History of hospitalization for 24 hours or longer, excluding elective procedures, within the 6 weeks (42 days) prior to Screening."}
• {"criterion_text":"- Liver test results elevated more than 2-fold above the upper limit of normal for gamma-glutamyl transferase, bilirubin (total), aspartate aminotransferase (AST) or alanine aminotransferase (ALT), unless a diagnosis of Gilbert syndrome. For history of Gilbert syndrome, the limit is extended to 3-fold above the upper limit of normal."}
• {"criterion_text":"- Concurrent or previous use of the following medications within the time periods specified below. a. Rituximab within 6 months (180 days) prior to randomization (Day 1); b. Intravenous immunoglobulin (IVIg) and plasma exchange (PLEX) within 4 weeks (28 days) prior to randomization (Day 1)."}
• {"criterion_text":"- Receipt of any live vaccine within 30 days prior to randomization (Day 1) or expected to receive a live vaccine during the study."}
• {"criterion_text":"- Clinically significant drug or alcohol abuse in the opinion of the Investigator."}
• {"criterion_text":"- Known hypersensitivity to any of the study drug ingredients."}
• {"criterion_text":"- For persons of childbearing potential, a positive serum pregnancy test during Screening or a positive urine pregnancy test (with confirmatory serum pregnancy test) at randomization."}
• {"criterion_text":"- Females who are breastfeeding or planning to breastfeed at any time during the study."}
• {"criterion_text":"- Participation in another clinical study of an investigational drug within 90 days or 5 half-lives of the investigational agent (whichever is longer) prior to randomization (Day 1)."}
• {"criterion_text":"- Clinical features that, in the opinion of the Investigator, are consistent with MG crisis/exacerbation at the time of the Screening visit or at any time between Screening and randomization."}
• {"criterion_text":"- Any other overlapping condition for which the condition or treatment of the condition may affect the study assessments or outcomes."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Diagnosis of SLE or family history (defined as a parent or sibling) of SLE."}
• {"criterion_text":"- Diagnosis of an autoimmune disorder other than gMG. Exceptions for other autoimmune disorders (except SLE) may be granted following Medical Monitor review and approval on a case-by-case basis."}
• {"criterion_text":"- An antinuclear antibodies (ANA) titer of ≥ 1:320, or positive for both ANA (any titer) and anti-double stranded (ds) DNA antibodies."}
• {"criterion_text":"- Known complement deficiency or history of positive titer for anti-C1 antibodies."}
• {"criterion_text":"- Prior history (at any time) of N. meningitidis infection."}
• {"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 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."}
• {"criterion_text":"- Currently or previously on complement inhibitors, or currently on antineonatal Fc receptor (FcRN) agents. Participants who were previously on anti-FcRN agents and took their last dose at least 5 half-lives or 90 days, whichever is greater, prior to randomization (Day 1) may be considered after review and approval by the Medical Monitor."}
• {"criterion_text":"- Any thymic surgery/biopsy within 1 year of Screening."}
• {"criterion_text":"- Any known or untreated thymoma. Past thymoma with resection (if surgery/resection done at least 1 year prior to Screening) is allowed, if no recurrence within 6 months prior to Screening or confirmed during Screening period (confirmed by computerized tomography scan or magnetic resonance imaging of the chest)."}
• {"criterion_text":"- Any history of thymic carcinoma or thymic malignancy."}

Primary endpoints

• {"endpoint_text":"- Safety and tolerability of DNTH103 up to Week 13: Incidence of TEAEs and treatment-emergent SAEs up to Week 13 (end of the RCT period)","definition_or_measurement_approach":"Incidence (count and proportion) of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs) recorded up to Week 13 (end of randomized controlled treatment period)."}

Secondary endpoints

• {"endpoint_text":"- Efficacy: Change from baseline to Week 13 in MG-ADL scale score","definition_or_measurement_approach":"Change from baseline to Week 13 in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score."}
• {"endpoint_text":"- Efficacy: Change from baseline to Week 13 in Quantitative Myasthenia Gravis (QMG) scale score","definition_or_measurement_approach":"Change from baseline to Week 13 in the Quantitative Myasthenia Gravis (QMG) score."}
• {"endpoint_text":"- Efficacy: Change from baseline to Week 13 in Myasthenia Gravis Composite (MGC) scale score","definition_or_measurement_approach":"Change from baseline to Week 13 in the Myasthenia Gravis Composite (MGC) score."}
• {"endpoint_text":"- Pharmacokinetics/Pharmacodynamics: Serum concentrations and PK parameters, including Cmax and Cmin","definition_or_measurement_approach":"Measurement of serum DNTH103 concentrations and calculation of PK parameters including maximum concentration (Cmax) and minimum/ trough concentration (Cmin)."}
• {"endpoint_text":"- Pharmacokinetics/Pharmacodynamics: PD parameters (eg, CH50 [complement hemolysis 50%]) in serum ex vivo","definition_or_measurement_approach":"Measurement of pharmacodynamic markers ex vivo in serum, e.g., CH50 (complement hemolysis 50%)."}
• {"endpoint_text":"- Immunogenicity: Incidence and titer of antidrug antibodies against DNTH103levels against DNTH103","definition_or_measurement_approach":"Assessment of incidence and titers of anti-drug (antibody) responses against DNTH103 (ADA testing and titration)."}
• {"endpoint_text":"- Safety and tolerability over 52 weeks in the OLE: Incidence of TEAEs and treatment-emergent SAEs up to Week 52 in the OLE","definition_or_measurement_approach":"Incidence (count and proportion) of TEAEs and treatment-emergent SAEs recorded up to Week 52 during the open-label extension (OLE) period."}

Denmark

Earliest CTIS Part Ii Submission Date

25-06-2024

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

587

Number Of Sites

1

Number Of Participants

4

Poland

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

08-02-2026

Processing Time Days

598

Number Of Sites

7

Number Of Participants

6

France

Earliest CTIS Part Ii Submission Date

21-06-2024

Latest Decision Or Authorization Date

08-11-2024

Processing Time Days

140

Number Of Sites

4

Number Of Participants

4

Netherlands

Earliest CTIS Part Ii Submission Date

25-06-2024

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

140

Number Of Sites

1

Number Of Participants

4

Norway

Earliest CTIS Part Ii Submission Date

08-07-2024

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

127

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

12-06-2024

Latest Decision Or Authorization Date

03-02-2026

Processing Time Days

601

Number Of Sites

2

Number Of Participants

6

Czechia

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

03-02-2026

Processing Time Days

589

Number Of Sites

1

Number Of Participants

2

Sweden

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

141

Number Of Sites

2

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

04-02-2025

Latest Decision Or Authorization Date

28-02-2025

Processing Time Days

24

Number Of Sites

4

Number Of Participants

24

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

Operational trial responsibilities (sponsorDuties codes: 1,11,12,13,14,2,5,6,8 as listed)

Name

QPS LLC

Responsibilities

sponsorDuties code 4 (as listed)

Third parties

• {"country":"Ireland","full_name":"Millmount Healthcare Limited","duties_or_roles":"QP release (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Kcas LLC","duties_or_roles":"sponsorDuties code 4","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Wuxi Biologics Co. Ltd.","duties_or_roles":"Drug product manufacturing, bulk packaging and labeling (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"sponsorDuties code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Merative US LP","duties_or_roles":"sponsorDuties code 7","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Croatia","full_name":"Worldwide Clinical Trials d.o.o.","duties_or_roles":"Multiple operational sponsor duties including codes 1,11,12,13,14,2,5,6,8 (as listed in sponsorDuties)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"sponsorDuties code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties code 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"Home IP administration, subjects travel management (sponsorDuties code 15)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Quipment","duties_or_roles":"MG specific equipment (sponsorDuties code 15)","organisation_type":"Non-Pharmaceutical company"}