Clinical trial NCT05462522: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of RO7303509 in Participants With Systemic Sclerosis
Official title: A Phase Ib, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple-Ascending Doses of RO7303509 in Participants With Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Systemic Sclerosis
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of RO7303509 treatment in participants with systemic sclerosis (SSc) during a multiple-ascending-dose (MAD) portion of the trial. In the MAD phase, increasing doses of study drug will be tested sequentially. For each dose tested, the MAD stage will consist of a treatment period of 12 weeks followed by either a safety follow-up period of 13 weeks or continued treatment in an optional open-label safety extension (OSE) stage of 52 weeks to assess the long-term safety. All patients in the OSE stage will receive RO7303509 and no patient will receive placebo.


Eligibility criteria: Inclusion Criteria:

Inclusion Criteria for the MAD Stage:

* Weight of 45-150 kg at screening
* Diagnosis of SSc, as defined by 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria and ≤ 10 years disease duration from first non-Raynaud's symptom
* Agreement to remain abstinent or use an effective contraceptive method among males and females with childbearing potential for 4 months after last dose of study drug

Inclusion Criteria for the OSE Stage:

* No clinically significant change in eligibility status
* Completion of the MAD and ability to roll over into the OSE within 5 days

Exclusion Criteria:

* Active rheumatic autoimmune disease other than SSc requiring treatment with disease-modifying therapy
* Pulmonary disease with forced vital capacity (FVC) ≤ 50% of predicted
* History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, hematologic, gastrointestinal, urologic, neurologic, or psychiatric disorders
* History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 4 months after the final dose of study drug
* Major surgery within 8 weeks prior to screening, or major planned surgery during the study or within 3 months after the final dose
* Positive hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody test at screening
* Any serious medical condition or abnormality in clinical laboratory tests

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 17 months
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Up to approximately 17 months
measure: Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Test Results
timeFrame: Up to approximately 17 months
measure: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: Up to approximately 17 months
Secondary outcomes:
measure: MAD Stage: Maximum Serum Concentration (Cmax) of RO7303509
timeFrame: Predose on Day 1 and at multiple timepoints up to Day 113 or early termination (ET) visit
measure: MAD Stage: Area Under the Concentration vs Time Curve (AUC) of RO7303509
timeFrame: Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
measure: MAD Stage: Time to Maximum Concentration (Tmax) of RO7303509
timeFrame: Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
measure: MAD Stage: Total Clearance (CL) of RO7303509
timeFrame: Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
measure: MAD Stage: Volume of Distribution (V) of RO7303509
timeFrame: Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
measure: MAD Stage: Half-Life (t1/2) of RO7303509
timeFrame: Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
measure: MAD and OSE Stage: Percentage of Participants With Anti-Drug Antibodies (ADAs) Against RO7303509
timeFrame: MAD Stage: Predose on Day 1 and at multiple timepoints up to Day 113 (Week 16) or ET visit; OSE Stage: Predose and multiple timepoints up to Week 52; (up to approximately 1.3 years)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: New York
country: United States
facility: Hospital For Special Surgery
state: New York
city: Dallas
country: United States
facility: Metroplex Clinical Research Centre
state: Texas
city: Buenos Aires
country: Argentina
facility: Hospital de Alta Complejidad en Red ?El Cruce? Dr. Néstor Kirchner ? S.A.M.I.C.
city: San Miguel de Tucumán
country: Argentina
facility: Clinica Mayo de U.M.C.B. S.R.L
city: Leuven
country: Belgium
facility: UZ Leuven
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire de Grenoble - Albert Michallon
city: Paris
country: France
facility: Hopital Cochin
city: Pessac
country: France
facility: CHU de Bordeaux
city: Rennes
country: France
facility: CHRU Rennes
city: Strasbourg
country: France
facility: Hopitaux Universitaires
city: Toulouse
country: France
facility: Hopital Purpan
city: Haifa
country: Israel
facility: Rambam Medical Center - PPDS
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Lublin
country: Poland
facility: Zespol Poradni Specjalistycznych REUMED
city: Almada
country: Portugal
facility: Hospital Garcia de Orta
city: Coimbra
country: Portugal
facility: Centro Hospitalar E Universitário de Coimbra EPE
city: San Juan
country: Puerto Rico
facility: The Alliance Medical Sciences Campus
city: Belgrade
country: Serbia
facility: Institute of Rheumatology Belgrade - PPDS
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d Hebron
city: Sevilla
country: Spain
facility: Hospital Quironsalud Infanta Luisa
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: