An open label, phase I/II study investigating the safety and efficacy of the bispecific T-cell engaging antibody cizutamig (BCMAxCD3) in patients with immune-mediated inflammatory diseases – the SPLENDID Trial

Condition studied

Severe, treatment refractory primary Sjögren’s disease (pSjD), Severe, treatment refractory idiopathic inflammatory myopathy (IIM), Severe, treatment refractory systemic sclerosis (SSc), Severe, treatment-refractory, seropositive (anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor positive) rheumatoid arthritis (RA)

Investigational medicinal product(s)

Eligibility

Primary endpoint

Primary endpoint (Safety): Incidence and grading of severity of Cytokine Release Syndrome (CRS), Immune Cell Associated Neurotoxicity Syndrome (ICANS) and treatment-emergent adverse events (TEAE) and serious adverse events (SAE) due to IMP until 28 days after the last administration of BCMAxCD3 TCE cizutamig

Endpoint detail

Main disease specific clinical efficacy (SSc): rCRISS30/5 response at Week 16, Main disease specific clinical efficacy (IIM): moderate or major total improvement score (TIS) response at week 16, Main disease specific clinical efficacy (pSjD): change from baseline in European Alliance of Associations for Rheumatology (EULAR) Sjögren's syndrome disease activity index (ESSDAI) at week 16, Main disease specific clinical efficacy (RA): American College of Rheumatology (ACR) 20 response at week 16, Main disease specific clinical efficacy (ONLY for those with interstitial lung disease [ILD] at baseline for all IMIDs): Change in forced vital capacity (FVC) and diffusion capacity of the lungs for carbon monoxide (DLCO) at 16 and 52 weeks compared to baseline, Further disease specific clinical efficacy (SSc): rCRISS 20/30/50 response at week 16 and 52, Further disease specific clinical efficacy (SSc): Change in modified Rodnan skin score (mRSS) at 16, 24 and 52 weeks compared to baseline, Further disease specific clinical efficacy (SSc): Change in Troponin T levels at 16, 24 and 52 weeks compared to baseline, Further disease specific clinical efficacy (SSc): Change in EULAR SSc Impact Score (Sclero-ID) over time compared to baseline, Further disease specific clinical efficacy (SSc): Change in digital ulcer count at 16, 24 and 52 weeks compared to baseline, Further disease specific clinical efficacy (IIM): Minimal, moderate or major TIS response at 16, 24 and 52 weeks, Further disease specific clinical efficacy (IIM): Change in TIS score from baseline at 16, 24 and 52 weeks, Further disease specific clinical efficacy (IIM): Change in muscle memory test 8 (MMT8) at 16, 24 and 52 weeks compared to baseline, Further disease specific clinical efficacy (IIM): Change in physician’s global assessment of extramuscular activity at 16, 24 and 52 weeks compared to baseline, Further disease specific clinical efficacy (IIM): Change in cutaneous disease area and severity index (CDASI) at 16, 24 and 52 weeks (in case of DM) compared to baseline, Further disease specific clinical efficacy (IIM): Change in CK, aldolase and Troponin T levels over time compared to baseline, Further disease specific clinical efficacy (pSjD): Change from baseline in ESSDAI at week 24 and 52, Further disease specific clinical efficacy (pSjD): Change from baseline in EULAR Sjögren’s syndrome patient reported index (ESSPRI) at week 16, 24 and 52, Further disease specific clinical efficacy (pSjD): Percentage (%) of participants with decrease in ESSPRI ≥1 or 15% from baseline at 16, 24 and 52 weeks, Further disease specific clinical efficacy (pSjD): Percentage (%) of participants with decrease in ESSDAI ≥3 points from baseline at 16, 24 and 52 weeks, Further disease specific clinical efficacy (pSjD): Percentage (%) of participants with ESSDAI <5 at 16, 24 and 52 weeks, Further disease specific clinical efficacy (pSjD): Change from baseline in oral and ocular dryness numerical rating scale (NRS) at 16 and 52 weeks, Further disease specific clinical efficacy (pSjD): Percentage (%) of participants with increase of Schirmer's test ≥ 5 mm if abnormal baseline at 16 and 52 weeks, Further disease specific clinical efficacy (RA): American College of Rheumatology (ACR) 50/70 response at 16, 24 and 52 weeks., Further disease specific clinical efficacy (RA): ACR 20 response at week 24 and 52 weeks., Further disease specific clinical efficacy (RA): Disease acitivity score 28 (DAS28)-CRP / DAS28-ESR / simplified disease acitivity index (SDAI) / Boolean remission at 16, 24, and 52 weeks., Further disease specific clinical efficacy (RA): Proportion of patients with DAS28-CRP<3.2 at week 16, 24 and 52, Further disease specific clinical efficacy (RA): Change in DAS28-CRP / SDAI / clinical disease activity index (CDAI) at 16, 24, and 52 weeks compared to baseline., Further disease specific clinical efficacy (RA): Change in ESR values over time compared to baseline, General clinical response and patient reported outcomes in all IMID groups: Duration without disease-modifying antirheumatic drug (DMARD) therapy from week 5 to week 52, General clinical response and patient reported outcomes in all IMID groups: Time until clinical relapse or flare observed between week 5 and week 52, General clinical response and patient reported outcomes in all IMID groups: Number of flares from week 5 through week 52, General clinical response and patient reported outcomes in all IMID groups: Cumulative steroid dosage from week 5 to week 52, General clinical response and patient reported outcomes in all IMID groups: Change in levels of CRP over time compared to baseline, General clinical response and patient reported outcomes in all IMID groups: Change in hand strength over time compared to baseline, General clinical response and patient reported outcomes in all IMID groups: Change in patient’s global assessment (PtGA) of disease activity (VAS 0-100mm) over time compared to baseline, General clinical response and patient reported outcomes in all IMID groups: Change in physician’s global assessment (PhGA) of disease activity (VAS 0-100mm) over time compared to baseline, General clinical response and patient reported outcomes in all IMID groups: Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) over time compared to baseline, General clinical response and patient reported outcomes in all IMID groups: Change in Short Form 36 (SF-36, quality of life questionnaire) over time compared to baseline, General clinical response and patient reported outcomes in all IMID groups: Change in Health Assessment Questionnaire Disability Index (HAQ-DI) over time compared to baseline