eprintid: 10133468
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/13/34/68
datestamp: 2021-08-26 08:36:14
lastmod: 2021-09-27 22:35:28
status_changed: 2021-08-26 08:36:14
type: article
metadata_visibility: show
creators_name: Spiera, R
creators_name: Khanna, D
creators_name: Kuwana, M
creators_name: Furst, DE
creators_name: Frech, TM
creators_name: Hummers, L
creators_name: Stevens, W
creators_name: Matucci-Cerinic, M
creators_name: Baron, M
creators_name: Distler, O
creators_name: Dgetluck, N
creators_name: Bloom, BJ
creators_name: Dinh, Q
creators_name: White, B
creators_name: Denton, CP
title: A randomised, double-blind, placebo-controlled phase 3 study of lenabasum in diffuse cutaneous systemic sclerosis: RESOLVE-1 design and rationale
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G90
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
abstract: OBJECTIVES:
The multi-systemic, heterogenous nature of diffuse cutaneous systemic sclerosis (dcSSc) presents challenges in designing clinical studies that can demonstrate a treatment effect on overall disease burden. We describe the design of the first Phase 3 study in dcSSc patients where the American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score was chosen prospectively as the primary outcome. The CRISS measures key clinical disease parameters and patient-reported outcomes (PROs). 
METHODS:
RESOLVE-1 is a Phase 3, randomised, double-blind, placebo-controlled trial of dcSSc patients evaluating the efficacy and safety of lenabasum. Patients ≥18 years of age with dc-SSc and disease duration ≤6 years were eligible. Patients could continue stable background therapy for dcSSc, including stable immunosuppressive therapies. They were randomised to lenabasum 5 or 20 mg twice daily or placebo. The primary efficacy outcome was the mean change from baseline to 52 weeks in the ACR CRISS score. 
RESULTS:
The study enrolled 365 patients over 1.5 years at 77 sites in 13 countries in North America, Europe, Israel, and Asia-Pacific, with the last patient first visit on May 1, 2019. 
CONCLUSIONS:
RESOLVE-1 is the first Phase 3 interventional study to date in dcSSc to prospectively use the ACR CRISS as the primary efficacy outcome. Eligibility criteria allowed background therapy as might occur in clinical practice. This approach also facilitated timely patient enrolment. RESOLVE-1 provides a novel study design that may be used for future Phase 3 dcSSc studies to assess the holistic efficacy of therapy.
date: 2021-07-28
date_type: published
publisher: CLINICAL & EXPER RHEUMATOLOGY
official_url: https://www.clinexprheumatol.org/abstract.asp?a=16298
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1883513
lyricists_name: Denton, Christopher
lyricists_id: CPDEN87
actors_name: Denton, Christopher
actors_id: CPDEN87
actors_role: owner
full_text_status: public
publication: Clinical and Experimental Rheumatology
volume: 39
number: 4
pagerange: S124-S133
pages: 10
issn: 1593-098X
citation:        Spiera, R;    Khanna, D;    Kuwana, M;    Furst, DE;    Frech, TM;    Hummers, L;    Stevens, W;                                 ... Denton, CP; + view all <#>        Spiera, R;  Khanna, D;  Kuwana, M;  Furst, DE;  Frech, TM;  Hummers, L;  Stevens, W;  Matucci-Cerinic, M;  Baron, M;  Distler, O;  Dgetluck, N;  Bloom, BJ;  Dinh, Q;  White, B;  Denton, CP;   - view fewer <#>    (2021)    A randomised, double-blind, placebo-controlled phase 3 study of lenabasum in diffuse cutaneous systemic sclerosis: RESOLVE-1 design and rationale.                   Clinical and Experimental Rheumatology , 39  (4)   S124-S133.          Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10133468/1/Resolve%20trial%20methodology%20CXR-2021-for%20UCL%20upload.pdf