Clinical trial NCT05835986: A First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7507062 in Participants With Systemic Lupus Erythematosus
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-04-28
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Tocilizumab is an additional investigational medicinal product (IMP), which may be used at the investigator's discretion when required in case of clinical presentation of cytokine release syndrome (CRS).

Eligibility criteria: 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 should 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 item.
* 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.

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 cyclophosphamide, B-cell-depleting therapies, other biologic or targeted 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 5 years prior to the Screening visit (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).

Primary outcomes:
measure: Part 1: Number of Participants with Dose Limiting Adverse Events (DLAEs)
timeFrame: Day 1 through Day 29
measure: Part 2: Fractionated Dose Cohort: Number of Participants with DLAEs
timeFrame: Day 1 through to the end of the 28-day safety evaluation period
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 12 months
Secondary outcomes:
measure: Serum Concentration of RO7507062
timeFrame: Up to approximately 12 months
measure: Time to Maximum Serum Concentration (Tmax) of RO7507062
timeFrame: Up to approximately 12 months
measure: Maximum Serum Concentration (Cmax) of RO7507062
timeFrame: Up to approximately 12 months
measure: Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7507062
timeFrame: Up to approximately 12 months
measure: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of RO7507062
timeFrame: Up to approximately 12 months
measure: Apparent Terminal Half-Life (T1/2) of RO7507062
timeFrame: Up to approximately 12 months
measure: Terminal Rate Constant (λz) of RO7507062
timeFrame: Up to approximately 12 months
measure: Apparent Volume of Distribution (Vz/F) of RO7507062
timeFrame: Up to approximately 12 months
measure: Apparent Total Body Clearance (CL/F) of RO7507062
timeFrame: Up to approximately 12 months
measure: Number of Participants with Anti-Drug Antibodies (ADAs) to RO7507062
timeFrame: Up to approximately 12 months
Other outcomes:
Locations:
city: Barranquilla
country: Colombia
facility: Clinica De La Costa
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Monteria
country: Colombia
facility: Oncomedica S.A.
city: Montpellier
country: France
facility: Hôpital Saint Eloi
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Duesseldorf
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: Guadalajara
country: Mexico
facility: CREA Hospital Mexico Americano
state: Jalisco
city: Mexico City
country: Mexico
facility: Hospital Angeles De Lindavista
state: Mexico CITY (federal District)
city: Leiden
country: Netherlands
facility: Centre For Human Drug Research
city: Lima
country: Peru
facility: Clínica San Juan Bautista CSJB
city: Pozna?
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Warszawa
country: Poland
facility: MICS Centrum Medyczne Damiana, Walbrzyska
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny- Panstwowy Instytut Badawczy
city: Bloemfontein
country: South Africa
facility: FARMOVS (Pty) Ltd
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol Uni
city: London
country: United Kingdom
facility: UCL Hospital NHS Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: