Clinical trial NCT05232825: A Phase III, Non-Inferiority, Randomized, Open-Label, Parallel Group, Multicenter Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Radiological And Clinical Effects Of Subcutaneous Ocrelizumab Versus Intravenous Ocrelizumab In Patients With Multiple Sclerosis
Official title: A Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Radiological And Clinical Effects Of Subcutaneous Ocrelizumab Versus Intravenous Ocrelizumab In Patients With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Relapsing Multiple Sclerosis
Primary Progressive Multiple Sclerosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-02-10
Enrollment: 236
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the pharmacokinetics, pharmacodynamics, safety, immunogenicity, and radiological and clinical effects of subcutaneous (SC) administration of ocrelizumab compared with the intravenous (IV) infusion of ocrelizumab in patients with either relapsing multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS).


Eligibility criteria: Inclusion Criteria:

* Diagnosis of PPMS or RMS according to the revised McDonald 2017 criteria (Thompson et al. 2018)
* EDSS score, 0-6.5, inclusive, at screening
* Neurological stability for ≥30 days prior to both screening and baseline
* Disease duration from onset of MS symptoms of less than 15 years for patients with EDSS score \<2.0 at screening
* For females participants, without reproductive potential may be enrolled if post-menopausal, unless receiving a hormonal therapy for menopause or if surgically sterile
* For females of childbearing potential, agreement to remain abstinent or use adequate contraceptive methods

Exclusion Criteria:

* Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV anti microbials within 8 weeks prior to and during screening or treatment with oral anti microbials within 2 weeks prior to and during screening
* History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
* History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
* Immunocompromised state
* Receipt of a live-attenuated vaccine within 6 weeks prior to randomization Influenza vaccination is permitted if the inactivated vaccine formulation is administered
* Inability to complete an MRI or contraindication to gadolinium administration
* Contraindications to mandatory premedications for IRRs, including closed-angle glaucoma for antihistamines
* Known presence of other neurologic disorders
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude patient from participating in the study
* History of or currently active primary or secondary (non-drug-related) immunodeficiency
* Pregnant or breastfeeding, or intending to become pregnant during the study and 6 or 12 months
* Lack of peripheral venous access
* History of alcohol or other drug abuse within 12 months prior to screening
* Treatment with any investigational agent within 24 weeks prior to screening or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
* Participants who have previously received anti-CD20s if the last treatment was less than 2 years before screening, and/or if B-cell count is below lower limit of normal, and/or the discontinuation of the treatment was due to safety reasons or lack of efficacy
* Previous treatment with cladribine, atacicept, and alemtuzumab
* Previous treatment with fingolimod, siponimod, ponesimod, or ozanimod within 6 weeks of baseline
* Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
* Previous treatment with natalizumab within 4.5 months of baseline
* Treatment with mitoxantrone within 2 years prior to baseline visit or evidence of cardiotoxicity following mitoxantrone use or a cumulative lifetime dose of more than 60 mg/m2
* Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label.
* If the washout requirements are not described in the applicable local label, then the wash out period must be 5 times the half-life of the medication. The PD effects of the previous medication must also be considered when determining the required time for washout.
* Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
* Any previous history of transplantation or anti-rejection therapy
* Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
* Systemic corticosteroid therapy within 4 weeks prior to screening
* Positive screening tests for active, latent, or inadequately treated hepatitis B
* Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
* Any additional exclusionary criterion as per ocrelizumab (Ocrevus®) local label, if more stringent than the above

Primary outcomes:
measure: Serum ocrelizumab area under the concentration-time curve (AUCW1-12)
timeFrame: Day 1 to Week 12
Secondary outcomes:
measure: Maximum serum concentration (Cmax) of ocrelizumab SC in patients with MS
timeFrame: Day 1 to Week 12
measure: Total number of T1Gd+ lesions as detected by brain MRI
timeFrame: Weeks 8 and 24
measure: Total number of new or enlarging T2 lesions as detected by brain MRI
timeFrame: Weeks 12 and 24
measure: Percentage of participants with Adverse Events
timeFrame: Day 1 to Week 48
measure: Incidence of treatment-emergent antidrug antibodies to ocrelizumab after SC or IV administration
timeFrame: Day 1 to Week 48
measure: Incidence of treatment-emergent antibodies to rHuPH20
timeFrame: Day 1 to Week 48
measure: Proportion of participants achieving CD19+ B cell level ≤5 cells/uL
timeFrame: Day 1 to Week 48
Other outcomes:
Locations:
city: Maitland
country: United States
facility: Neurology Associates PA
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Owosso
country: United States
facility: Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis
state: Michigan
city: Dayton
country: United States
facility: UC Health Neurology
state: Ohio
city: Greenville
country: United States
facility: Premier Neurology
state: South Carolina
city: Cordova
country: United States
facility: Neurology Clinic PC
state: Tennessee
city: Salvador
country: Brazil
facility: Clinica Amo - Assistencia Medica Em Oncologia
state: Bahia
city: Vitoria
country: Brazil
facility: CEDOES - Diagnóstico e Pesquisa
state: Espírito Santo
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny
city: Hradec Králové
country: Czechia
facility: Charles University, Medical faculty, Hradec Kralove
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava
city: Ostrava-Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Pardubice
country: Czechia
facility: Pardubicka Krajska Nemocnice
city: Praha 2
country: Czechia
facility: Fakultni poliklinika VFN
city: Praha
country: Czechia
facility: Fakultni nemocnice Motol
city: Teplice
country: Czechia
facility: Krajska zdravotni a.s Nemocnice Teplice o.z.
city: Roma
country: Italy
facility: Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
state: Lazio
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
state: Lazio
city: Montichiari
country: Italy
facility: Ospedale Civile di Montichiari
state: Lombardia
city: Pozzilli
country: Italy
facility: IRCCS Istituto Neurologico Neuromed
state: Molise
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials
city: Hastings
country: New Zealand
facility: Hawkes Bay Hospital
city: Bydgoszcz
country: Poland
facility: Neurocentrum Bydgoszcz sp. z o.o
city: Katowice
country: Poland
facility: Care Clinic
city: Lodz
country: Poland
facility: Centrum Neurologii Krzysztof Selmaj
city: Wroc?aw
country: Poland
facility: Przychodnia EuroMediCare
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
state: Sevilla
city: Santa Cruz De Tenerife
country: Spain
facility: Complejo Hospitalario Nuestra Señora de la Candelaria
state: Tenerife
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Istanbul
country: Turkey
facility: Bakirkoy State Mental Hospital
city: Istanbul
country: Turkey
facility: Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi
city: Izmir
country: Turkey
facility: Katip Celebi University Ataturk Training and Research Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli University Hospital
city: Süleymanpa?a
country: Turkey
facility: Namik Kemal Universitesi Sagli Uygulama ve Arastirma Hastanesi
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: