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

Amgen

Status and phase: Not yet enrolling; Phase 2

Conditions: Active Refractory Rheumatoid Arthritis; Systemic Lupus Erythematosus

Treatments: Drug: Blinatumomab; Drug: Inebilizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06570798

2024-514382-19 (EudraCT Number)

20240033

Details and patient eligibility

About

The main objective is to assess the safety and tolerability of inebilizumab in adult participants with active and refractory systemic lupus erythematosus (SLE) with nephritis (Subprotocol A) and to assess the safety and tolerability of subcutaneous (SC) blinatumomab in adult participants with active and refractory (SLE) with nephritis (Subprotocol B) and in adult participants with active refractory rheumatoid arthritis (RA) (Subprotocol C).

Enrollment: 110 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subprotocol A and B: Diagnosis of SLE and lupus nephritis (LN) 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:

  1. Antinuclear antibodies (ANA) ≥ 1:80
  2. Anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies elevated to above normal range as established by central laboratory (ie, positive results)
  3. Anti-Smith antibodies elevated to above normal (ie, positive results).

• Subprotocol A and B: SLEDAI-2K ≥ 8.

• 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. Renal biopsy must have been performed within 6 months before enrollment. The local biopsy report will be used. A central review center will confirm the eligibility.

• Subprotocol A and B: Inadequate response, for lack of efficacy or intolerance after 6 months 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:

  1. UPCR ≥ 1.5 mg/mg
  2. Less than 50% of proteinuria improvement in the past 3 months.

• 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 < 45 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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110 participants in 8 patient groups

Subprotocol A: Inebilizumab 3 Doses

Experimental group

Description:

Participants will receive 3 doses of inebilizumab administered via an intravenous (IV) infusion.

Treatment:

Drug: Inebilizumab

Subprotocol A: Inebilizumab 4 Doses

Experimental group

Description:

Participants will receive 4 doses of inebilizumab administered via an IV infusion.

Treatment:

Drug: Inebilizumab

Subprotocol B: Blinatumomab Low-dose

Experimental group

Description:

Participants will receive blinatumomab low-dose administered via SC injection.

Treatment:

Drug: Blinatumomab

Subprotocol B: Blinatumomab Medium-dose

Experimental group

Description:

Participants will receive blinatumomab medium-dose administered via SC injection.

Treatment:

Drug: Blinatumomab

Subprotocol B: Blinatumomab High-dose

Experimental group

Description:

Participants will receive blinatumomab high-dose administered via SC injection.

Treatment:

Drug: Blinatumomab

Subprotocol C: Blinatumomab Low-dose

Experimental group

Description:

Participants will receive blinatumomab low-dose administered via SC injection.

Treatment:

Drug: Blinatumomab

Subprotocol C: Blinatumomab Medium-dose

Experimental group

Description:

Participants will receive blinatumomab medium-dose administered via SC injection.

Treatment:

Drug: Blinatumomab

Subprotocol C: Blinatumomab High-dose

Experimental group

Description:

Participants will receive blinatumomab high-dose administered via SC injection.

Treatment:

Drug: Blinatumomab