A Study to Investigate the Safety, Tolerability, and Processing by the Body of Intravenous and Subcutaneous RO7121932 in Participants With Multiple Sclerosis.

Multiple Sclerosis Clinical Trial

Official title:

Official Title: A Multiple-Center, Non-randomized, Open-label, Adaptive, Single-Ascending Dose (Part 1 and Part 2) and Multiple-Ascending Dose (Part 3) Parallel, Phase IB Study to Investigate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of RO7121932 Following Intravenous (Part 1) and Subcutaneous Administration (Parts 2 and 3) in Participants With Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05704361
• Other study ID #: BP42230
• Secondary ID: 2020-004122-33
• Status: Recruiting
• Phase: Phase 1
• Start date: August 11, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BP42230 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 primary purpose of the study is to evaluate the safety and tolerability of single ascending intravenous (IV) (Part 1) and subcutaneous (SC) (Part 2) doses of RO7121932 and multiple ascending SC (Part 3) doses of RO7121932 in participants with multiple sclerosis (MS).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 129
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Expanded Disability Status Scale (EDSS) score =7.0 at Screening

• Participants with relapsing multiple sclerosis (RMS) or progressive multiple sclerosis (PMS) who fulfil international panel criteria for diagnosis (McDonald 2017 criteria)

• Participants not treated with any approved MS treatment at Screening and not planning to start on any MS therapy during the study (including follow-up)

• Female participants must practice abstinence or otherwise use contraception

Exclusion Criteria:

• Evidence of clinical disease activity as defined by any clinical relapse within 3 months prior to screening, or by >1 clinical relapse within 12 months prior to screening

• Evidence of magnetic resonance imaging (MRI) activity as defined by the presence of = 1 Gadolinium-enhancing T1 lesion in the screening MRI scan or by = 4 new or enlarging T2 lesions in the screening scan as compared to a reference scan

• Participants who have active progressive multifocal leukoencephalopathy (PML), have had confirmed PML, or have a high degree of suspicion for PML

• Known presence of other neurological disorders that may mimic MS including but not limited to: neuromyelitis optica spectrum disease, Lyme disease, untreated Vitamin B12 deficiency, neurosarcoidosis, cerebrovascular disorders, and untreated hypothyroidism

• Known active or uncontrolled bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds, including participants exhibiting symptoms consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 6 weeks prior to Day 1

• Participants with a current diagnosis of epilepsy

• Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal, or other major diseases

• History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening. Basal or squamous cell carcinoma of the skin that has been excised and is considered cured and in situ carcinoma of the cervix treated with apparent success by curative therapy >1 year prior to screening is not exclusionary

• Any concomitant disease that may require treatment with systemic corticosteroids or immunosuppressants during course of the study

• History of currently active primary or secondary (non-drug-related) immunodeficiency

• History of hypersensitivity to biologic agents or any of the excipients in the formulation

• Only for cohorts where CSF samples are planned to be collected: Participants with a history of spinal cord compression, raised intra-cerebral pressure, clinically significant vertebral joint pathology or any other current abnormalities in the lumbar region which could prevent the lumbar puncture procedure.

Prior/Concomitant Therapy:

• Treatment with any approved MS treatment at Screening. Participants may become eligible after completion of a washout period prior to acquiring any screening laboratory tests but should not be withdrawn from therapies for the sole purpose of meeting eligibility for the trial

• Previous treatment with RO7121932, alemtuzumab, cladribine, mitoxantrone, cyclophosphamide, total body irradiation, bone marrow transplantation, and hematopoietic stem cell transplantation. For the USA only, previous treatment with daclizumab

• Previous treatment with anti-CD20 B-cell-depleting therapies (e.g., rituximab, ocrelizumab, or ofatumumab)

• <12 months prior to acquiring any screening laboratory tests,

• =12 months prior to acquiring any screening laboratory tests, if B-cells are outside the normal range, or not back to individual baseline ± 20% (if data are available),

• If discontinuation of a prior B-cell depletion therapy was motivated by safety reasons

• Current or prior treatment with natalizumab (if <24 months prior to acquiring any screening laboratory tests)

Prior/Concurrent Clinical Study Experience:

• Participation in an investigational drug medicinal product or medical device study within 30 days before Screening or within five times the pharmacodynamic (PD) or pharmacokinetic (PK) half-life (if known), whichever is longer

Diagnostic Assessments:

• Positive result on human immunodeficiency virus (HIV1) and HIV2, hepatitis C, or hepatitis B

• Participants with suicidal ideation or behavior within 6 months prior to Screening or participants who, in the Investigator's judgment, pose a suicidal or homicidal risk

• Vaccination with a live or live-attenuated vaccine within 6 weeks prior to Day 1

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• RO7121932 IV - SAD
Part 1: Participants will receive a single dose of RO7121932 administered as IV infusion.
• RO7121932 SC - SAD
Part 2: Participants will receive a single dose of RO7121932 administered as SC injection.
• RO7121932 - MAD
Part 3: Participants will receive multiple doses of RO7121932 administered as SC injections.

Locations

Country	Name	City	State
Belgium	UZ Gent	Gent
Canada	Montreal Neurological Institute and Hospital; Pharmacy Department	Montreal	Quebec
Germany	Universitätsklinikum "Carl Gustav Carus"; MS Center Dresden	Dresden
Germany	Universitätsmedizin Göttingen Georg-August-Universität; Klinik für Neurologie	Göttingen
Germany	Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum	München
Germany	Universitätsklinikum Münster Klinik u. Poliklinik f. Neurologie	Münster
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Tel Aviv Sourasky Medical Center; Department of Neurology	Tel Aviv
Italy	Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari	Milano	Lombardia
Italy	IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla	Milano	Lombardia
Moldova, Republic of	ARENSIA Exploratory Medicine Phase I, PMSI Republican Clinical Hospital	Chisinau
Poland	Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz	Gda?sk
Poland	Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial Neurologiczny	Grudzi?dz
Poland	MedPolonia	Poznan
Poland	Osrodek Badan Klinicznych Euromedis	Szczecin
Poland	Instytut Psychiatrii i Neurologii II Klinika Neurologiczna	Warszawa
Poland	SPSK nr 1; Klinika Neurologii	Zabrze
Portugal	Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)	Braga
Romania	ARENSIA Exploratory Medicine, County Emergency Hospital	Cluj-Napoca
United States	UC Health, LLC.	Cincinnati	Ohio
United States	Yale University Multiple Sclerosis Center	New Haven	Connecticut
United States	Stanford University Medical Center; Stanford Neuroscience Health Center	Stanford	California
United States	University of South Florida	Tampa	Florida
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Israel,  Italy,  Moldova, Republic of,  Poland,  Portugal,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1, Part 2 and 3: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) with Severity of AEs Measured According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5)		Day 1 to Day 169 for part 1 and part 2; Day 1 to Day 197 for part 3
Primary	Part 1, Part 2 and Part 3: Percentage of Participants With Abnormal Laboratory Findings		Day 1 to Day 169 for part 1 and part 2; Day 1 to Day 197 for part 3
Primary	Part 1, Part 2 and Part 3: Percentage of Participants With Abnormal Vital Signs and Electrocardiogram (ECG) Parameters		Day 1 to Day 169 for part 1 and part 2; Day 1 to Day 197 for part 3
Primary	Part 1, Part 2 and Part 3: Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is an interview-based instrument used to assess baseline incidence of suicidal ideation and behavior. The assessment includes "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings are provided for severity of ideation (if present), from 0 to 5. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates suicidal ideation or behavior, with 5 being the most severe.	Day 1 to Day 169 for part 1 and part 2; Day 1 to Day 197 for part 3
Primary	Part 2 and Part 3: Percentage of Participants with Local Pain at the Site of Injection Assessed Using the Visual Analog Scale (VAS)	VAS is a 100 millimetre (mm) horizontal visual analog scale with values 0 to 100 mm to indicate pain. The following cutpoints on the pain VAS will be considered in the interpretation of the pain data: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). A higher score indicates greater pain intensity.	Day 1, 2, 5, 8 for part 2; Day 1, 2, 5, 8, 15, 22, 29, 36 for part 3
Primary	Part 2 and Part 3: Percentage of Participants with Local Injection Site Reaction Using Local Injection-site Symptom Assessment (LISSA)	LISSA form will be used to assess the participant's injection site for the following categories of reactions: Burning, Itching, Bruising, Erythema (redness), Hive formation, Induration, Swelling, Ecchymosis, Sensitivity, Papules, Stinging, Blister, Cold sensation, and Other. These reactions will be described using the following scale: Unable to assess, less than a dime (<18 mm/<0.7 inches), a dime (18 mm/0.7 inches), a nickel (21 mm/0.8 inches), a quarter (24 mm/1 inch), a half dollar (31 mm/1.2 inches), larger than a half dollar (>31 mm/>1.2 inches). A higher score indicate high injection site reactions.	Day 1,2, 5, 8 for part 2; Day 1, 2, 5, 8, 15, 22, 29, 36 for part 3
Secondary	Part 1, Part 2 and Part 3 (Week 1 and Week 4): Time to Maximum Observed Concentration (Tmax) of RO7121932		Day 1 to Day 169 for part 1 and part 2; Days 1, 2, 5 and, 22 for part 3
Secondary	Part 1, Part 2 and Part 3 (Week 1 and Week 4): Maximum Observed Serum Concentration (Cmax) of RO7121932		Day 1 to Day 169 for part 1 and part 2; Days 1, 2, 5 and, 22 for part 3
Secondary	Part 1, Part 2 and Part 3 (Week 1 and Week 4): Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours (h) (AUC0-168h) Postdose		Day 1 (predose) to Day 8 (168 hours post-dose) for parts 1, 2, and 3 (Week 1) and Day 22 (predose) to Day 29 (168 hours post-dose) for part 3 (Week 4)
Secondary	Part 1 and Part 2: Area Under the Serum Concentration-Time Curve up to the Last Measurable Concentration (AUClast)		Day 1 to Day 169 for part 1 and part 2
Secondary	Part 1 and Part 2: AUC From Time 0 to Infinity (AUCinf)		Day 1 to Day 169 for part 1 and part 2
Secondary	Part 1: Total Body Clearance (CL) Of RO7121932		Day 1 to Day 169
Secondary	Part 2 and Part 3 (Week 4): Apparent Clearance (CL/F) of RO7121932		Day 1 to Day 169 for part 2; Day 22 to Day 29 for part 3
Secondary	Part 1, Part 2 and Part 3: Terminal Rate Constant of RO7121932		Day 1 to Day 169 for part 1 and part 2; Day 22 to Day 197 for part 3
Secondary	Part 1, Part 2 and Part 3: Apparent Terminal Half-Life (T1/2) of RO7121932		Day 1 to Day 169 for part 1 and part 2; Day 22 to Day 197 for part 3
Secondary	Part 3: Trough Concentrations (Ctrough) of RO7121932		Day 1 to Day 197
Secondary	Part 1 and Part 3: Cerebrospinal Fluid (CSF) Concentration of RO7121932		Screening, Day 2 to Day 169 for part 1; Screening, Day 2 to Day 197 for part 3
Secondary	Part 1, Part 2 and Part 3: Percentage of Participants With Anti-RO7121932 Antibodies		Predose on Day 1, and on Days 8, 22, 29, 57, 85, 169 for part 1; Predose on Day 1, and on Days 8, 22, 57, 85, 169 for part 2 Predose on Days 1, 8, 15, 22, and on Days 29, 57, 85, 120, 197 for part 3
Secondary	Part 1, Part 2 and Part 3: Time Course of B-cell Frequencies in Blood		Screening, Days 1, 2, 8, 22, 57, 85, 169 for part 1; Screening, Days 1, 2, 8, 22, 57, 85, 169 for part 2; Screening, Days 1, 2, 8, 15, 22, 57, 85, 120, 197 for part 3
Secondary	Part 1 and Part 3: Time Course of B-cell Frequencies in CSF		Screening, Day 2 to 169 for part 1; Screening, Day 2 to 197 for part 3
Secondary	Part 1, Part 2 and Part 3: Change From Baseline in B-cell Frequencies in Blood		Screening, Days 1, 2, 8, 22, 57, 85, 169 for part 1; Screening, Days 1, 2, 8, 22, 57, 85, 169 for part 2; Screening, Days 1, 2, 8, 15, 22, 57, 85, 120, 197 for part 3
Secondary	Part 1 and Part 3: Change From Baseline in B-cell Frequencies in CSF		Screening, Day 2 to 169 for part 1; Screening, Day 2 to 197 for part 3