KYV-101 for Generalized myasthenia gravis

Inclusion criteria

• {"criterion_text":"- 1. Patients must be ≥ 18 to ≤ 75 years of age with a diagnosis of generalized MG\n- 9. No change in dose of acetylcholinesterase inhibitors for ≥2 weeks prior to screening\n- 11. No use of rituximab (or any other anti-CD20 or CD19 monoclonal antibody) within 12 weeks prior to screening.\n- 12. No use of FcRn inhibitors within 4 weeks prior to screening.\n- 10. No use of intravenous immune globulin (IVIG) or plasmapheresis (PLEX) within 4 weeks of screening or pre-dose baseline (unless this is part of their SOC treatment regimen).\n- 2. Presence of autoantibodies to AChR or MuSK at screening (not just historical).\n- 3. Myasthenia Gravis Foundation of America (MGFA) Class IIb-IV.\n- 4. MG-ADL total score of ≥6 at screening and confirmed at pre-dose baseline.\n- 5. QMG total score of ≥11 at screening and confirmed at pre-dose baseline.\n- 6. Failed treatment with 2 or more immunosuppressive/immunomodulatory therapies, or failed at least 1 immunosuppressive therapy and required chronic plasmapheresis, or IVIG to control symptoms. a. Failed treatment may consist of either lack of sufficient efficacy with an adequate trial, intolerable adverse effects, or contraindications to therapy, as determined by the investigator.\n- 7. In Germany only, failed standard-of-care immunosuppressive and immunomodulatory therapies including complement inhibitors and FcRn modulators. o Failed treatment may consist of either lack of sufficient efficacy with an adequate trial, intolerable adverse effects, or contraindications to therapy, as determined by the investigator. o Failure of chronic plasmapheresis or IVIG to control symptoms.\n- 8. On a stable dose of glucocorticoids and/or other immunotherapies for ≥1 month prior to screening. For azathioprine, being on a stable dose for ≥2 months prior to screening is required."}

Exclusion criteria

• {"criterion_text":"- 1. Unable to washout or interrupt autoimmune therapy prior to apheresis as specificed in protocol\n- 10. Patients requiring chronic anticoagulation therapy that cannot be discontinued for medical procedures (such as apheresis\n- 11. Prior treatment with gene therapy product or cellular immunotherapy (eg, CAR T) requiring vector integration and directed at any target.\n- 12. Plan to receive live, attenuated vaccine after signing ICF (inactive vaccines, such as the flu vaccine, are allowed).\n- 13. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to KYV-101 or its excipients, including dimethyl sulfoxide; or to CYC, FLU, or tocilizumab.\n- 14. Have evidence of latent or active TB infection, as documented by a positive QuantiFERON-TB Gold test at screening.\n- 15. Positive hepatitis B surface antigen (HBsAg) at screening. Patients who are HBsAg negative but hepatitis B core antibody (HBcAb) positive must have negative hepatitis B virus (HBV) DNA testing.\n- 16. Positive hepatitis C serology confirmed by polymerase chain reaction (PCR).\n- 17. Positive serology for human immunodeficiency virus (HIV).\n- 18. Positive screening test for SARS-CoV-2, by PCR or rapid antigen testing (not antibody testing). Note: Patients with a positive SARS-CoV-2 at screening can be enrolled if the patient has all 3 of the following: no active signs or symptoms of SARS-Cov-2 infection after 10 days, a negative repeat PCR or rapid antigen test, and no sequelae or complications of SARS-CoV-2 infection.\n- 19. Any laboratory values at screening exceeding the cutoff values\n- 2. Co-occurring neurological autoimmune disease (ie, Lambert-Eaton Myasthenic Syndrome) or any disease affecting the neuromuscular junction or muscle causing weakness (eg, myositis, myopathy, motor neuropathy)\n- 20. Any of the following vital sign parameters at rest: • Systolic Blood Pressure (mmHg) < 95 or > 150 • Diastolic Blood pressure (mmHg) < 55 or > 95 • Heart Rate < 50 or > 100 bpm • Oral Temperature > 37.7° C/afebrile • Respiratory rate < 12 or > 20 bpm (Note: Up to 3 assessments of blood pressure, heart rate, and respiratory rate may be made within a 24-hour period)\n- 21. Pregnant or breastfeeding, plans to become pregnant/breastfeed or father a child, risk of unintentional pregnancy/fathering, or plans to donate eggs/sperm in the timeframe provided in the protocol\n- 3. History of stroke (with residual sequalae and/or risk for recurrence), seizure (even if well controlled on antiepileptics), neurodegenerative disease, altered mental status (unexplained and/or recent/current), or uncontrolled/severe psychiatric disease\n- 4. Any serious and/or uncontrolled medical condition that, in the investigator’s judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol, including but not limited to, clinically significant cardiac or pulmonary disease.\n- 5. History of primary immunodeficiency, organ or allogeneic bone marrow transplant, or splenectomy.\n- 6. Active, uncontrolled, viral, bacterial, or systemic fungal infection or recent history of repeated infections.\n- 7. Previous or concurrent malignancy with the following exceptions: a. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening). b. In situ carcinoma (eg, of the cervix or breast), treated curatively and without evidence of recurrence for at least 3 years prior to screening. c. A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening.\n- 8. Major surgery within 4 weeks prior to apheresis or planned within 4 weeks after KYV-101 administration. For surgery planned after 4 weeks post KYV-101 administration, discuss with the sponsor\n- 9. Thymectomy ≤ 12 months of screening or planned during the study."}

Primary endpoints

• {"endpoint_text":"- 1. Phase 2: Incidence and severity of AEs and laboratory abnormalities.","definition_or_measurement_approach":"Incidence and severity of adverse events (AEs) and laboratory abnormalities as reported/recorded during Phase 2 (no further definition provided in the supplied data)."}
• {"endpoint_text":"- 2. Phase 2: MG-ADL change from baseline at 24 weeks.","definition_or_measurement_approach":"Change from baseline in MG-ADL (Myasthenia Gravis Activities of Daily Living) score at 24 weeks."}
• {"endpoint_text":"- 3. Phase 3: MG-ADL change from baseline at 24 weeks for KYV-101 compared to SOC (co-primary)","definition_or_measurement_approach":"Between-arm comparison of change from baseline in MG-ADL at 24 weeks (KYV-101 vs standard-of-care)."}
• {"endpoint_text":"- 4. Phase 3: QMG change from baseline at 24 weeks for KYV-101 compared to SOC (co-primary)","definition_or_measurement_approach":"Between-arm comparison of change from baseline in QMG (Quantitative Myasthenia Gravis) score at 24 weeks (KYV-101 vs standard-of-care)."}

Secondary endpoints

• {"endpoint_text":"- 1. Phase 3: MGC change from baseline at 24 weeks for KYV-101 compared to SOC.","definition_or_measurement_approach":"Change from baseline in MGC (Myasthenia Gravis Composite) score at 24 weeks, compared between KYV-101 and SOC."}
• {"endpoint_text":"- 2. Phase 3: Percent change from baseline in anti-AChR or anti-MuSK antibody levels at week 24 for KYV-101 compared to SOC.","definition_or_measurement_approach":"Percent change from baseline in anti-AChR or anti-MuSK antibody levels at week 24, compared between KYV-101 and SOC."}
• {"endpoint_text":"- 3. Phase 3: Proportion of patients with a ≥3 point improvement from baseline in MG-ADL at 24 weeks for KYV-101 compared to SOC.","definition_or_measurement_approach":"Proportion of patients achieving ≥3-point improvement in MG-ADL at 24 weeks, compared between arms."}
• {"endpoint_text":"- 4. Phase 3: Proportion of patients with MSE at week 24 for KYV-101 compared to SOC.","definition_or_measurement_approach":"Proportion of patients with MSE at week 24 (MSE not further defined in the supplied data), compared between arms."}
• {"endpoint_text":"- 5. Phase 3: MG-QoL15r change from baseline at 24 weeks for KYV-101 compared to SOC.","definition_or_measurement_approach":"Change from baseline in MG-QoL15r (Myasthenia Gravis Quality of Life 15 revised) at 24 weeks, compared between arms."}
• {"endpoint_text":"- 6. Phase 3: Incidence and severity of AEs and laboratory abnormalities.","definition_or_measurement_approach":"Incidence and severity of adverse events and laboratory abnormalities during Phase 3 (no further definition provided in the supplied data)."}

Germany

Earliest CTIS Part Ii Submission Date

16-04-2024

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

661

Number Of Sites

8

Number Of Participants

17

Primary sponsor

Full Name

Kyverna Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

sponsorDuties codes: [1,10,11,12,4,5,6,7]

Name

Icon (Lr) Limited

Responsibilities

sponsorDuties codes: [4]

Name

Pra International

Responsibilities

sponsorDuties codes: [4]

Name

PPD Global Central Labs

Responsibilities

sponsorDuties codes: [4]

Name

Icon Laboratory Services Inc.

Responsibilities

Flow Cytometry (sponsorDuties code: 15)

Third parties

• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Pra International","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Molecularmd Corp.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: [1,10,11,12,4,5,6,7]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Precision for Medicine GmbH","duties_or_roles":"Cytokine Analysis (sponsorDuties code: 15)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Precision For Medicine Inc. (Frederick)","duties_or_roles":"sponsorDuties codes: [5]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Definitive Media Corp.","duties_or_roles":"ePRO eCOA collection (sponsorDuties code: 15)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Central IRB (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Elevatebio Base Camp Inc.","duties_or_roles":"Manufacturing (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"eDC Database (sponsorDuties code: 15)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Wuxi Advanced Therapies Inc.","duties_or_roles":"Manufacturing (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Pharma Bio-Research Group","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"SYNLAB International GmbH","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Flow Cytometry (sponsorDuties code: 15)","organisation_type":"Laboratory/Research/Testing facility"}