A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of RO7303509 in Participants With Systemic Sclerosis

Systemic Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05462522
• Other study ID #: GA43360
• Secondary ID: 2021-004578-68
• Status: Recruiting
• Phase: Phase 1
• Start date: January 16, 2023
• Est. completion date: November 28, 2025

Study information

• Verified date: May 2024
• Source: Genentech, Inc.
• Contact: Reference Study ID Number: GA43360 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 28, 2025
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• RO7303509
RO7303509 will be administered as SC injection monthly, as specified in each treatment group.
• Placebo
RO7303509 matching placebo will be administered as SC injection monthly, during the MAD stage.

Locations

Country	Name	City	State
Argentina	Hospital de Alta Complejidad en Red ?El Cruce? Dr. Néstor Kirchner ? S.A.M.I.C.	Buenos Aires
Argentina	Clínica Adventista Belgrano	Estomba
Argentina	Clinica Privada Independencia	Munro Buenos Aires
Argentina	Clinica Mayo de U.M.C.B. S.R.L	San Miguel de Tucumán
Belgium	UZ Leuven	Leuven
Belgium	CHU de Liège	Liège
France	Centre Hospitalier Universitaire de Grenoble - Albert Michallon	La Tronche
France	Hopital Cochin	Paris
France	CHU de Bordeaux	Pessac
France	CHRU Rennes	Rennes
France	Hopitaux Universitaires	Strasbourg
France	Hopital Purpan	Toulouse
Germany	Universitaetsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	Universitätsklinikum Freiburg	Freiburg
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Medical Center - PPDS	Haifa
Israel	Meir Medical Center; Rheumatology Dept	Kfar Saba
Israel	Sheba Medical Center - PPDS	Ramat Gan
Poland	Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy; Klinika Reumatologii	Bydgoszcz
Poland	Szpital Specjalistyczny im. Jozefa Dietla w Krakowie	Kraków
Poland	Zespol Poradni Specjalistycznych REUMED	Lublin
Poland	Lecznica MAK-MED NZOZ	Nadarzyn
Poland	Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher	Warszawa
Portugal	Hospital Garcia de Orta	Almada
Portugal	Centro Hospitalar E Universitário de Coimbra EPE	Coimbra
Puerto Rico	The Alliance Medical Sciences Campus; University Hospital	San Juan
Serbia	Institute of Rheumatology Belgrade - PPDS	Belgrade
Serbia	Military Medical Academy	Belgrade
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d Hebron	Barcelona
Spain	C.H. Regional Reina Sofia - PPDS	Cordoba
Spain	Hospital de Merida	Merida	Badajoz
Spain	Hospital Quironsalud Infanta Luisa	Sevilla
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United Kingdom	Royal Free Hospital; Haematology	London
United Kingdom	Salford Royal Hospital	Salford
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Metroplex Clinical Research Centre	Dallas	Texas
United States	Hospital For Special Surgery	New York	New York
United States	Stanford University	Palo Alto	California
United States	Mayo Clinic - Cancer Center - Rochester - PPDS	Rochester	Minnesota
United States	University of Toledo Medical Center	Toledo	Ohio
United States	Medstar Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  France,  Germany,  Israel,  Poland,  Portugal,  Puerto Rico,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)		Up to approximately 17 months
Primary	Number of Participants With Clinically Significant Change From Baseline in Vital Signs		Up to approximately 17 months
Primary	Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Test Results		Up to approximately 17 months
Primary	Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters		Up to approximately 17 months
Secondary	MAD Stage: Maximum Serum Concentration (Cmax) of RO7303509		Predose on Day 1 and at multiple timepoints up to Day 113 or early termination (ET) visit
Secondary	MAD Stage: Area Under the Concentration vs Time Curve (AUC) of RO7303509		Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
Secondary	MAD Stage: Time to Maximum Concentration (Tmax) of RO7303509		Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
Secondary	MAD Stage: Total Clearance (CL) of RO7303509		Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
Secondary	MAD Stage: Volume of Distribution (V) of RO7303509		Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
Secondary	MAD Stage: Half-Life (t1/2) of RO7303509		Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit
Secondary	MAD and OSE Stage: Percentage of Participants With Anti-Drug Antibodies (ADAs) Against RO7303509		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)