A Phase 2a Master Protocol Assessing Inebilizumab and Blinatumomab in Autoimmune Diseases

Launched by AMGEN · Aug 22, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at two medications, inebilizumab and blinatumomab, to see how safe and well-tolerated they are for adults with certain autoimmune diseases, specifically systemic lupus erythematosus (SLE) with kidney problems (lupus nephritis) and rheumatoid arthritis (RA) that hasn't responded to other treatments. The trial is divided into three parts, each focusing on different groups of participants: one group with SLE and kidney issues, another with the same condition but receiving a different medication, and the last group with RA.

To be eligible for the trial, participants need to have been diagnosed with these conditions and show that previous treatments haven’t worked for them. For instance, those with SLE must have specific autoantibodies in their blood and active kidney problems, while RA participants must have had active disease despite trying various medications. If you join the trial, you'll be monitored closely by medical professionals to ensure your safety. It's also important to note that the trial is not yet recruiting participants, so there’s no immediate action needed if you’re interested.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Subprotocol A and B: Diagnosis of SLE according to 2019 European League Against Rheumatism and the American College of Rheumatology (ACR) classification criteria.
• * Subprotocol A and B: Participant must be positive for at least one of the following autoantibodies at screening (performed by central laboratory) or through documented history:
• • 1. Antinuclear antibodies (ANA) ≥ 1:80
• • 2. Anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies elevated to above normal range (ie, positive results)
• • 3. Anti-Smith antibodies elevated to above normal (ie, positive results).
• • Subprotocol A and B: Active, biopsy-proven, proliferative LN demonstrating class III or class IV with or without co-existing features of Class V LN according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria. The local biopsy report will be used.
• • Subprotocol A and B: Inadequate response, loss of response or intolerance to at least 1 therapy (Subprotocol A) or 2 therapies (Subprotocol B) at the maximally tolerated doses as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines (KDIGO, 2024). Inadequate response is defined as: UPCR ≥ 1.0 mg/mg
• * Subprotocol A and B: If receiving any of the following medications, participants must be on these doses prior to day 1:
• • 1. Prednisone dose ≤ 20 mg/day (or its equivalent in other corticosteroid forms) and at a stable dose for 5 days
• • 2. Hydroxychloroquine dose ≤ 400 mg/day and at a stable dose for 4 weeks. Other equivalent antimalarials (chloroquine, quinacrine) are also accepted at a stable dose for 4 weeks.
• • 3. MMF dose ≤ 3 g/day or MPA dose ≤ 2160 mg/day and at a stable dose for 2 weeks.
• • 4. AZA dose ≤ 2 mg/kg/day and at a stable dose for 2 weeks.
• • Subprotocol C: Diagnosis of RA according to the 2010 ACR/ European Alliance of Associations for Rheumatology (EULAR) classification criteria.
• * Subprotocol C: Active disease defined as having all the following criteria:
• • 1. DAS28-CRP \> 3.2 at screening
• • 2. at least 6 tender joints at screening
• • 3. at least 6 swollen joints at screening
• * Subprotocol C: Refractory disease defined as:
• * Moderate to severe active disease despite having received treatment with:
• • 1. at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD), AND
• • 2. at least 2 biologic disease-modifying antirheumatic drugs (bDMARDs) of different mechanisms of action OR 1 bDMARD and at least 1 targeted synthetic disease-modifying antirheumatic drugs (tsDMARD).
• * Inadequate response or intolerance to csDMARDs, bDMARDs, and tsDMARDs should be defined as:
• • 1. Participant having active disease despite a minimum of 12 weeks of treatment with a csDMARD, bDMARD, or tsDMARD.
• • 2. Intolerance to treatment as defined by participant having experienced an adverse effect from treatment with a csDMARD, bDMARD, or tsDMARD.
• Exclusion Criteria:
• • Subprotocol A and B: Estimated glomerular filtration rate (eGFR) of \< 30 mL per minute per 1.73 m\^2 of body surface area (calculated using the Modification of Diet in Renal Disease \[MDRD\] formula, with screening laboratory results for serum creatinine value).
• • Subprotocol A and B: Significant likely irreversible organ damage related to SLE (eg, end-stage renal disease \[ESRD\]).
• • Subprotocol A and B: Any acute, severe lupus related flare during screening that needs immediate treatment.
• • Subprotocol A and B: A previous kidney transplant or planned transplant within study treatment period.
• • Subprotocol A and B: History of or current renal diseases (other than LN) that in the opinion of the investigator could interfere with the LN assessment and confound the disease activity assessment (eg, diabetic nephropathy).
• • Subprotocol A and B: Renal biopsy showing pure class V.
• • Subprotocol C: Prior history of current inflammatory joint disease other than RA including but not limited to systemic lupus erythematosus, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (eg, vasculitis, pulmonary fibrosis, or Felty's syndrome).
• • Subprotocol C: Functional Class IV as defined by the ACR classification of functional status in RA.