ALLOGENEIC UMBILICAL CORD BLOOD-DERIVED NATURAL KILLER CELLS, EX VIVO EXPANDED for Systemic sclerosis | Rheumatoid arthritis | Idiopathic inflammatory myopathies | Sjögren’s disease

Inclusion criteria

• {"criterion_text":"- 1. Male or female subjects ≥ 18 years of age.\n- 26. Total Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) > 6.\n- 27. Salivary Flow Rate > 0.1 mL/min on stimulation\n- 11. Evidence of Active IIM with subjects meeting at least two of the following criteria: a.\tMMT-8 score < 135/150 (indicating moderate-to-severe proximal muscle weakness) b.\tCK or aldolase level > 1.5 × ULN, consistent with active muscle injury. c.\tPhysician Global Disease Activity ≥ 4/10 on a visual analog scale (VAS). d.\tCDASI Activity Score (for DM patients) ≥ 14, indicating moderate-to-severe skin activity. e.\tMRI finding evidence of muscle edema or inflammation on STIR or T2-weighted imaging f.\tESR or CRP elevated, supportive of inflammatory activity (in context). g.\tPatient-reported symptoms of significant muscle fatigue or pain limiting daily activities.\n- 28. Presence of extra-glandular domain involvement such as articular, renal, cutaneous, pulmonary, CNS, hematologic, lung, kidney and/or peripheral neuronal involvement.\n- 29. Serological activity defined as hypocomplementemia or elevated CRP/ESR/IgG level, or cryoglobulins (excluding acute or chronic infection and other factors).\n- 30. Patient failure to prior glucocorticoid therapy and at least two other immunosuppressive agents after 3 months of therapy, such as, but not limited to, cyclophosphamide, azathioprine, MMF, methotrexate, rituximab, or belimumab.\n- 4. Women of childbearing potential and all male participants must agree to use a highly effective method of contraception for the duration of the trial or through at least 1 year after completing lymphodepleting chemotherapy dosing: Female contraceptive methods include: •\tCombined hormonal contraception with estrogen and progesterone to inhibit ovulation, including oral, intravaginal, and transdermal preparations •\tProgesterone-only hormonal contraception that inhibits ovulation, including oral, injectable, and implantable preparations •\tIntrauterine device •\tIntrauterine hormone-releasing system •\tBilateral tubal ligation •\tVasectomized partner (if the partner is the sole sexual partner of the female subject of childbearing potential participating in the study, and has undergone a successful vasoligation) •\tComplete abstinence from heterosexual intercourse Male contraceptive methods include: •\tVasectomy •\tComplete abstinence from heterosexual intercourse •\tBarrier contraceptives in combination with female partner's hormonal or barrier method\n- 5. Predicted diffusing capacity for carbon monoxide (DLCO) of ≥ 60% and a forced vital capacity (FVC) ≥ 70% at screening or within 3 months of screening with written documentation and report available.\n- 6. Left ventricular ejection fraction (LVEF) ≥ 45% and no evidence of pericardial effusion as determined preferably by an echocardiogram (ECHO) or by multigated acquisition (MUGA) scan if ECHO is not available at screening or within 3 months of screening with written documentation and report available.\n- 7. Screening laboratory values fulfilling the following requirements: a.\tAbsolute Neutrophil Count (ANC) ≥ 1500/mm3 b.\tPlatelets ≥ 100,000/mm3 c.\tHemoglobin ≥ 8 g/dL d.\tCreatinine Clearance > 45 mL/minute as estimated by CKD-EPI equation (2021) e.\tLiver Transaminases (ALT, AST) ≤ 2x Upper Limit of Normal\n- 19. For Subjects with Rheumatoid Arthritis (RA) Meet the 2010 ACR/EULAR classification criteria for RA\n- 8. Performance status defined as ACR Functional Classification of Class III or less.\n- 9. Clinical examination to rule out inflammatory foci in the body by the PI or by a relevant consultation per clinical indication.\n- 10. For Subjects with Idiopathic Inflammatory Myopathies (IIMs) Meet 2017 EULAR/ACR classification crite for IIM, with a probability score meeting the threshold for “probable” or “definite” IIM.\n- 12. Presence of at least one myositis-specific autoantibody (MSA). Acceptable MSAs include, but are not limited to, anti-Jo-1, anti-PL-7, anti-PL-12, anti-Mi-2, anti-SRP, anti-MDA5, anti-TIF1-γ, , and anti- SAE.\n- 13. Refractory IIM is defined as an inadequate response or intolerance to at least 3 months of glucocorticoid therapy and at least two other immunosuppressive agents, such as (but not limited to) azathioprine, methotrexate, intravenous immunoglobulin (IVIG), mycophenolate mofetil (MMF), leflunomide, tacrolimus, cyclosporine, cyclophosphamide, and rituximab.\n- 14. For dermatomyositis (DM) and polymyositis (PM) subjects only, cancer screening as follows: a.\tAge- and sex- appropriate cancer-screening (e.g., breast cancer, cervical cancer, colorectal cancer, lung cancer) within past 12 months as recommended by local or national guidelines b.\tPhysical examination within the past 12 months to screen for evaluable malignancies (e.g., breast and pelvic examination for female patients, testicular and rectal examination for male patients, skin examination for malignancy-associated DM features)\n- 15. For Subjects with Systemic Sclerosis (SSc) Meets the 2013 ACR/EULAR classification criteria for SSc (score ≥ 9).\n- 16. Meet the following criteria for disease severity: •\tSkin: mRSS ≥ 15 AND •\tOne or more of the following major organ involvements within previous 12 months: a)\tLung: Interstitial lung disease with significant forced vital capacity (FVC) decline and/or diffusion capacity (DLCO) decline, pulmonary hypertension. b)\tGI tract: Dysphagia, significant gastroesophageal reflux, gastric paresis, gastric bleeding, intestinal dysmotility c)\tHeart: new or worsening cardiomyopathy, pericardial effusion, or arrhythmias. d)\tRenal: History of scleroderma renal crisis now stabilized (≥ 6 months from event).\n- 17. Disease duration ≤ 3 years from first non-Raynaud’s symptom (to target immune-active phase).\n- 18. Refractory SSc as defined by inadequate response or intolerance to at least two immunosuppressive agents for 3 months such as but not limited to, mycophenolate mofetil, cyclophosphamide, methotrexate, rituximab, tocilizumab, hydroxychloroquine, or azathioprine.\n- 20. Rheumatoid Factor (RF) or Anti Citrullinated Protein Antibody (ACPA) positive.\n- 2. Ability to understand the requirements of the study and provide written informed consent.\n- 3. Willingness to comply with the study procedures.\n- 21. High-sensitivity C-reactive protein (hs-CRP) > 3 mg/L or Erythrocyte Sedimentation Rate (ESR) > 28 mm/hr.\n- 22. Subjects must have refractory rheumatoid arthritis, defined as: a.\tAn inadequate response, loss of response, or intolerance to at least one conventional synthetic DMARD (csDMARD) (e.g., an inadequate response, loss of response, or intolerance at an approved dose after at least 3 months of treatment or for the duration as described in the approved label) AND b.\tAn inadequate response, loss of response, or intolerance to at least two biologic or targeted synthetic DMARDs (b/tsDMARDs) with different mechanisms of action, such as a TNF inhibitor, abatacept, rituximab, tocilizumab, JAK inhibitor.\n- 23. Minimum of 6 swollen joint counts (SJC) and 6 tender joint counts (TJC) of 66 swollen and 68 tender joint count evaluations.\n- 24. Disease Activity Score 28 (DAS28-ESR) > 3.2 at screening.\n- 25. For Subjects with Sjögren’s Disease (SjD) Meet 2016 ACR/EULAR criteria for Sjogren’s Disease with confirmatory diagnosis in the 24 weeks preceding the first day of the screening visit."}

Exclusion criteria

• {"criterion_text":"- 1. For All Subjects Subjects who received cyclophosphamide within 28 days of Day 1.\n- 19. Study subjects with any of the following tuberculosis (TB) criteria: •\tKnown active TB infection. •\tHistory of active TB infection involving any organ system or findings in other organ systems consistent with TB, unless adequately treated according to WHO/CDC therapeutic guidance and proven to be fully recovered upon consultation with a TB specialist. •\tLatent TB infection (LTBI) by QuantiFERON®-Gold Plus test unless appropriate prophylaxis is initiated at least 4 weeks prior to study medication dosing and will be continued to completion of prophylaxis. •\tHigh risk of acquiring TB infection, e.g., known close exposure to another person with active TB infection within 3 months prior to screening or significant time spent in a health care delivery setting or institution where individuals infected with TB are housed and where the risk of transmission is high within 3 months prior to Screening.\n- 20. Currently pregnant or lactating.\n- 3. Subjects who received the following agents in the relevant washout periods before screening: •\tMethotrexate within 4 weeks, except in patients with RA in whom methotrexate will be held from Day 1 until Week 4 and restarted on Week 5. •\tMycophenolate Mofetil (MMF) within 4 weeks •\tAzathioprine within 2 weeks •\tLeflunomide within 8 weeks or accelerated with cholestyramine •\tIVIG within 4 weeks •\tHydroxychloroquine within 4 weeks •\tAdditional washout requirements provided\n- 21. Any medical, psychological, familial, or sociological condition that, in the opinion of the principal investigator, would impair the subject's ability to receive study treatment or comply with study requirements.\n- 22. Subjects with a prior history of hypogammaglobulinemia or with low IgG levels (< 600 mg/dL).\n- 4. Known hypersensitivity or contraindication to any drug products or any component of the drug products they plan to receive (e.g., cyclophosphamide, fludarabine, rituximab, AlloNK®).\n- 5. History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies or dimethyl sulfoxide (DMSO).\n- 6. Prior treatment with any B-cell depleting therapy within 6 months of the start of the planned lymphodepletion regimen (e.g., rituximab, obinutuzumab, other depleting anti-CD20, anti-CD19 or anti-CD22 antibodies).\n- 7. Prior treatment with any autologous or allogeneic cell therapy approach using genetically modified immune cells (e.g., T, NK, macrophages, or gamma-delta T-cells modified with chimeric antigen receptors [CAR]).\n- 8. History of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant, or are due to receive such transplantation.\n- 11. Any of the following suggestive of significant heart disease: •\tModerate to severe congestive heart failure (New York Heart Association class III or IV), •\tRecent (within past 6 months) myocardial infarction, coronary stenting •\tClinically relevant or significant electrocardiogram (ECG) abnormalities, including ECG with QT interval corrected for heart rate (QTc) > 500 msec.\n- 9. Known past or current malignancy except for: •\tCervical carcinoma of stage 1B or less, •\tNoninvasive basal cell or squamous cell skin carcinoma, •\tNoninvasive, superficial bladder cancer, •\tProstate cancer with a current prostate specific antigen (PSA) level < 0.1 ng/mL •\tAny curable cancer with a complete response duration of > 2 years.\n- 10. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to IIMs, SSc, RA, or SjD which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.\n- 2. Subjects who received prednisone > 10 mg within 48 hours prior to Day 1.\n- 12. Have clinically significant central nervous system (CNS) involvement at screening (e.g., stroke, seizure, brain tumors, neurodegenerative conditions, or CNS infections) that, in the opinion of the investigator, would compromise the patient’s health, safety, or ability to participate in the trial.\n- 13. Have a planned surgical procedure or a history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the principal investigator, makes the subject unsuitable for the study.\n- 14. Have any signs or symptoms of illness or infection that require systemic treatment, or any infection or infestation which, in the opinion of the investigator, would compromise the patient’s health, safety, or ability to participate in the trial.\n- 15. Have received any vaccinations (live or inactivated) within 4 weeks of Day 1.\n- 16. Human immunodeficiency virus (HIV) infection, based on laboratory testing performed during the screening period.\n- 17. Active Hepatitis C virus (HCV) infection, based on laboratory testing performed during screening period. •\tAnti-HCV antibody positivity will require reflex HCV RNA testing. HCV RNA positivity will be exclusionary.\n- 18. Hepatitis B (HBV) infection •\tHBsAg positive •\tHBcAb positive will require reflex HBV DNA testing. HBV DNA positivity will be exclusionary."}

Primary endpoints

• {"endpoint_text":"- Dose- limiting toxicities will be assessed at each dose level in a 3+3 design to determine the MTD and/or MAD.\n- Idiopathic Inflammatory Myopathies: TIS ≥ 60\n- Systemic Sclerosis: rCRISS ≥ 50\n- Rheumatoid Arthritis: Disease Activity Score 28 (DAS28 - ESR) < 2.6\n- Sjögren’s Disease: Improvement from baseline in Clinical EULAR Sjogren's Syndrome Disease Activity Index (ClinESSDAI) of ≥ 4","definition_or_measurement_approach":"DLTs: assessed at each dose level using a traditional 3+3 design to determine MTD and/or MAD. Disease-specific efficacy endpoints measured at Week 52: TIS ≥ 60 for IIM; rCRISS ≥ 50 for systemic sclerosis; DAS28-ESR < 2.6 for rheumatoid arthritis; ClinESSDAI improvement ≥ 4 for Sjögren’s disease."}

Secondary endpoints

• {"endpoint_text":"- 1. Safety will be assessed according to the SoA by monitoring AEs, co-meds, physical exams, ECGs, vital signs, and lab test findings. AEs will be coded using MedDRA and graded for severity by the Investigator using the Common Terminology Criteria for Adverse Events Version 5.0, with the exception of the following adverse events:\n- 2. CRS events will be assessed by ASTCT grading; ICANS events will be assessed by ASTCT grading; GvHD diagnosis and grading of GvHD should follow the MAGIC criteria\n- 3. The following biomarkers will be measured at baseline and at the timepoints specified in the SoA (Table 1): •\tAutoantibodies for RA: Rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA, e.g. anti-cyclic citrullinated peptide [CCP]). •\tAutoantibodies for IMM: anti-synthetase autoantibodies (e.g. anti-Jo-1, PL-7, PL-12, EJ, OJ, KS), anti-SRP, anti-Mi-2, anti-p140)\n- 4. •\tAutoantibodies for SSc: e.g. anti-CENP-A/B/C, anti-topo-1, anti-RNAPI/III, anti-Scl70, anti-Jo1, anti-SSA. •\tAutoantibodies for SjD: Disease associated, e.g., anti-Ro (anti-SS-A) and anti-La (anti-SS-B)\n- 6. Secondary Humoral Immunogenicity Endpoint Humoral immunogenicity will be determined by measuring anti-HLA antibodies specific to AlloNK® in subjects’ serum as specified in the SoA (Table 1). Exploratory objectives and associated endpoints are provided in the protocol.","definition_or_measurement_approach":"Safety monitored per Schedule of Assessments (SoA) including AEs (MedDRA coding) graded by CTCAE v5.0; CRS and ICANS graded by ASTCT; GvHD per MAGIC criteria. Biomarkers and autoantibodies measured at baseline and specified SoA timepoints; humoral immunogenicity assessed by anti-HLA antibody assays as specified in SoA/Table 1."}

Methods

• Doctor-to-Doctor letters to referring physicians (country-specific doctor-to-doctor documents present: e.g., Doctor_to_Doctor_letter_ROU, Dr-to-Dr letters for DE, FR, ES, IT, PL). Target audience: healthcare professionals/physicians.
• Patient-facing trial flyers and one-page trial summaries for distribution at clinics and referral sites (country-specific flyers present for RO, BG, PL, PT, DE, FR, ES, IT, etc.). Target audience: potential patient participants in site countries.
• Digital advertising / PatientWing digital ads and PatientWing materials (documents: PatientWing_Materials_Digital_Ads_DEU_ENG_Public, PatientWingMaterials_ESP_SPA_Digital-Ads). Target audience: patients via online/digital channels.
• Recruitment arrangements documents and privacy policies tailored per country (K1/K2 recruitment arrangements documents submitted per country). Channel: site-based recruitment coordination and local outreach; country-specific versions provided.
• Site-based referrals and investigator network outreach (materials include trial flyers and doctor-to-doctor letters targeted at rheumatology/clinical immunology clinics).

Romania

Earliest CTIS Part Ii Submission Date

20-05-2025

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

258

Number Of Sites

2

Number Of Participants

2

Bulgaria

Earliest CTIS Part Ii Submission Date

07-08-2025

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

204

Number Of Sites

2

Number Of Participants

2

Poland

Earliest CTIS Part Ii Submission Date

14-08-2025

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

165

Number Of Sites

3

Number Of Participants

2

Portugal

Earliest CTIS Part Ii Submission Date

04-08-2025

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

177

Number Of Sites

2

Number Of Participants

2

Germany

Earliest CTIS Part Ii Submission Date

30-07-2025

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

180

Number Of Sites

2

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

08-08-2025

Latest Decision Or Authorization Date

22-02-2026

Processing Time Days

198

Number Of Sites

3

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

14-08-2025

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

167

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

04-08-2025

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

214

Number Of Sites

3

Number Of Participants

2

Primary sponsor

Full Name

Artiva Biotherapeutics Inc.

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

Sponsor duties codes: [1,12,13,2,3,5,7,8,9] (multiple operational responsibilities per submission)

Name

PPD International Holdings LLC

Responsibilities

Sponsor duties codes: [4]

Name

Q2 Solutions LLC

Responsibilities

Sponsor duties codes: [4] (laboratory/testing services)

Name

Q Squared Solutions Limited

Responsibilities

Sponsor duties codes: [4]

Third parties

• {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Clinical Ink Inc.","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"sponsorDuties codes: [10, 6]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Artiva Biotherapeutics Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Tempus Compass LLC","duties_or_roles":"sponsorDuties codes: [8]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties codes: [14, 15] (includes study labeling of authorized IMP products and responsible for QP certification of authorized IMP products, where required)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: [1,12,13,2,3,5,7,8,9]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"sponsorDuties codes: [15] (patient Concierge Services and Compensation)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Cryoport France","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}