A Study of CC-97540, CD-19-Targeted Nex-T CAR T Cells, in Participants With Severe, Refractory Autoimmune Diseases

Juno Therapeutics

Status and phase

Enrolling

Phase 1

Conditions

Systemic Sclerosis

Idiopathic Inflammatory Myopathy

Systemic Lupus Erythematosus

Treatments

Drug: Fludarabine

Drug: CC-97540

Drug: Tocilizumab

Drug: Cyclophosphamide

Study type

Interventional

Funder types

Industry

Other

Identifiers

NCT05869955

2023-503823-24 (EudraCT Number)

CA061-1001

Details and patient eligibility

About

The purpose of this study is to establish the tolerability, preliminary efficacy, and pharmacokinetics of CC-97540 in participants with severe, refractory autoimmune diseases.

Enrollment

129 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Diagnosis of Systemic Lupus Erythematosus (SLE) defined as follows:.

i) Fulfilling the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria of SLE.

ii) Presence of anti-dsDNA, anti-histone, anti-chromatin, anti-Ro (anti-SS-A), anti-La (anti-SS-B), or anti-Sm antibodies at screening.

SLE disease activity.

i) Active disease at screening, with recent ≥ 1 major organ system with a BILAG A score (excluding musculoskeletal, mucocutaneous, and/or constitutional organ system).

ii) Inadequate response to glucocorticoids and to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, obinutuzumab, cyclosporin, tacrolimus or voclosporin.

Diagnosis of Idiopathic Inflammatory Myopathy (IIM) defined as follows:.

i) Fulfilling the 2017 EULAR/ACR classification criteria for probable or definite IIM.

ii) Participant diagnosed with the following IIM subgroups: dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), and polymyositis (PM).

iii) Presence of at least 1 myositis specific (MSA), associated antibody (MAA), or ANA at screening or prior to screening.

IIM disease activity.

i) Severe muscle AND/OR skin involvement.

ii) Proof of activity as documented by:.

A. An active myositis-associated rash OR.

B. A recent muscle biopsy OR.

C. An elevated CK > 3 times the upper limit of normal OR.

D. Participants diagnosed IIM AND progressive Interstitial Lung Disease (ILD) on high-resolution computed tomography (HRCT)

iii) Inadequate response to glucocorticoids and at least 2 of the following treatments used for at least 3 months: azathioprine, methotrexate, cyclosporin A, tacrolimus, MMF, cyclophosphamide, leflunomide, IVIG, and rituximab.

Diagnosis of Systemic Sclerosis (SSc) defined as follows:.

i) Fulfilling 2013 EULAR/ACR classification criteria for SSc.

ii) Antinuclear Antibody (ANA) positive at screening or prior to screening.

SSc disease activity.

i) Participants diagnosed with diffuse cutaneous SSc OR diffuse or limited cutaneous SSc AND progressive ILD, AND.

ii) Inadequate response to at least 1 of the following treatments used for at least 3 months: mycophenolate, cyclophosphamide, rituximab, nintedanib, azathioprine, tocilizumab, or intravenous immunoglobulins (IVIG).

Exclusion Criteria

Diagnosis of drug-induced SLE rather than idiopathic SLE.
Other systemic autoimmune diseases (eg, multiple sclerosis, psoriasis, inflammatory bowel disease, etc) are excluded. Participants with type I autoimmune diabetes mellitus, thyroid autoimmune disease, Celiac disease, or secondary Sjögren's syndrome are not excluded.
SLE overlap syndromes including, but not limited to, rheumatoid arthritis, scleroderma, and mixed connective tissue disease, are excluded.
Present or recent clinically significant CNS pathology, within 12 months.
IIM disease activity.

i) Other forms of IIM: Inclusion Body Myositis, Amyopathic DM, any form of juvenile myositis.

ii) Myositis other than IIM, eg, drug-induced myositis and PM associated with HIV.

iii) Participants with severe muscle damage (Physician VAS for muscle damage in Myositis Damage Index > 7 cm on a 10 cm scale), permanent weakness due to a non-IIM cause (eg, stroke), or myositis with cardiac involvement.

SSc disease activity.

i) SSc related PAH requiring active treatment.

ii) Rapidly progressive SSc related lower GI (small and large intestines) involvement (requiring parenteral nutrition); active gastric antral vascular ectasia.

iii) Prior scleroderma renal crisis.