A First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7507062 in Participants With Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title:

An Open-label, Multicenter, Dose Escalation, First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered RO7507062 in Participants With Systemic Lupus Erythematosus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05835986
• Other study ID #: BP44315
• Secondary ID: 2022-502632-39-0
• Status: Recruiting
• Phase: Phase 1
• Start date: December 18, 2023
• Est. completion date: November 30, 2027

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: BP44315 https://forpatients.roche.com/
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RO7507062 in participants with systemic lupus erythematosus (SLE). The study will have 2 parts: Part 1 is a single ascending dose-finding (SAD) part and Part 2 is a dose escalation with fractionated dosing part.

Description:

Tocilizumab is an additional investigational medicinal product (IMP), which will be used when required in case of clinical presentation of cytokine release syndrome (CRS). Data on the efficacy of tocilizumab in ameliorating the symptoms of CRS related to RO7507062 will be collected in this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: November 30, 2027
• Est. primary completion date: November 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Participants must have a diagnosis of SLE according to the 2019 European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) Classification Criteria at least 24 weeks prior to Screening and must have been treated for SLE according to standard clinical practice.

• Presence of anti-double stranded DNA (dsDNA), anti-Smith (Sm), anti-ribonucleoprotein (RNP) or anti-Sjögren's syndrome antigen A (SS-A) above the upper limit of normal (ULN); or, positive anti-nuclear antibody (ANA; = 1:160).

• Active SLE disease, as demonstrated by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score of =4 with at least 1 positive clinical.

• For participants receiving oral corticosteroids (OCS), treatment with = 20 milligram per day (mg/day) prednisone or equivalent, during Screening, at a dose that has been stable for at least 7 days prior to Day 1.

• For participants receiving conventional immunosuppressants (e.g., azathioprine, sulfasalazine, mycophenolate mofetil [= 3.0 grams per day], mycophenolic acid [= 3 grams per day], methotrexate [oral, SC, or intramuscular routes]), and calcineurin inhibitors [oral]), treatment should be at a stable dose for at least 6 weeks prior to Screening and during Screening and expected to remain stable during the study.

• For transitioning participants, stable hormonal therapy 3-6 months prior to screening.

Exclusion Criteria:

• Active or unstable lupus-associated neuropsychiatric disease.

• Catastrophic or severe antiphospholipid syndrome within 12 months prior to Screening or during Screening.

• Presence of severe lupus-associated renal disease that is likely to require treatment with protocol-prohibited therapies.

• Organ-threatening SLE manifestations (e.g., active myocarditis) considered to be severe by the Investigator.

• Severe active systemic autoimmune disease other than SLE.

• Active infection of any kind, excluding fungal infection of the nail beds.

• History of serious recurrent or chronic infection, especially; recurring, chronic infections specifically related to respiratory issues.

• Moderate or severe chronic obstructive pulmonary disease (COPD).

• History of progressive multifocal leukoencephalopathy (PML).

• History of macrophage-activation syndrome and/or hemophagocytic lymphohistiocytosis.

• History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the past 5 years (with the exception of basal cell carcinoma, non melanoma skin cancer, and cervical cancer in situ, if these have been adequately treated and are considered cured).

• Intolerance or contraindication to study therapies including history of severe allergic or anaphylactic reactions to monoclonal antibodies (mAbs) or known hypersensitivity to any component of the RO7507062 injection.

• History of infection with hepatitis B virus (HBV), or positive serology indicative of current or past HBV infection.

• Human immunodeficiency virus (HIV; positive HIV antibody test) and active hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid [RNA]).

• Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection.

• Receipt of any anti- cluster of differentiation (CD)19 or anti-CD20 therapy such as blinatumomab, obinutuzumab, rituximab, ocrelizumab, or ofatumumab less than 6 months prior to screening or during screening.

• Receipt of Inhibitors of Janus kinase (JAK), Bruton tyrosine kinase, or tyrosine kinase 2 including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, and fenebrutinib,or any investigational agent within 30 days prior to screening or during screening.

• Receipt of Cyclophosphamide or a biologic therapy such as, but not limited to, adalimumab, etanercept, golimumab, infliximab, belimumab,ustekinumab, anifrolumab, secukinumab, or atacicept, within 4 weeks prior to enrollment.

• Active tuberculosis or history of recurring or severe active tuberculosis, or a positive Interferon Gamma Release Assay (IGRA). Latent tuberculosis which has been treated prior to baseline is not exclusive.

• Receipt of an investigational therapy (except severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] vaccines) within 30 days or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment and during the study.

• Immunoglobulin (IgG) level of <6 gram per liter (g/L).

• Estimated glomerular filtration rate (eGFR) <45 milliliter per minute (mL/min)/1.73-meter square (m^2).

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• RO7507062
RO7507062 solution for injection will be administered SC as specified in each treatment arm.
• Tocilizumab
Tocilizumab solution for infusion will be administered intravenously at 8 milligram per kilogram (mg/kg) for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.

Locations

Country	Name	City	State
Germany	Charité Research Organisation GmbH	Berlin
Netherlands	Centre For Human Drug Research; Research	Leiden
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu; Osrodek Badan Klinicznych Wczesnych Faz	Pozna?
Poland	MICS Centrum Medyczne Damiana, Walbrzyska	Warszawa
Poland	Wojskowy Instytut Medyczny- Panstwowy Instytut Badawczy; Centrum Wsparcia Badan Klinicznych	Warszawa
South Africa	FARMOVS (Pty) Ltd; University of the Free State, Pharmacology Building	Bloemfontein
Spain	Hospital Universitario Reina Sofia; Servicio de Reumatologia	Cordoba
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Reumatología	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Reumatologia	Madrid
United Kingdom	UCL Hospital NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Germany,  Netherlands,  Poland,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants with Dose Limiting Adverse Events (DLAEs)		Day 1 through Day 29
Primary	Part 2: Number of Participants with DLAEs		Day 8 through Day 36
Primary	Number of Participants with Adverse Events (AEs) and CRS	Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), and CRS, will be graded based on the American Society for Transplantation and Cell Therapy (ASTCT) criteria.	Up to approximately 12 months
Secondary	Serum Concentration of RO7507062		Up to approximately 12 months
Secondary	Time to Maximum Serum Concentration (Tmax) of RO7507062		Up to approximately 12 months
Secondary	Maximum Serum Concentration (Cmax) of RO7507062		Up to approximately 12 months
Secondary	Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7507062		Up to approximately 12 months
Secondary	Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUClast) of RO7507062		Up to approximately 12 months
Secondary	Apparent Terminal Half-Life (T1/2) of RO7507062		Up to approximately 12 months
Secondary	Terminal Rate Constant (?z) of RO7507062		Up to approximately 12 months
Secondary	Apparent Volume of Distribution (Vz/F) of RO7507062		Up to approximately 12 months
Secondary	Apparent Total Body Clearance (CL/F) of RO7507062		Up to approximately 12 months
Secondary	Number of Participants with Anti-Drug Antibodies (ADAs) to RO7507062		Up to approximately 12 months