Clinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of ACT-334441 in Subjects With Systemic Lupus Erythematosus

A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-response Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of ACT-334441 in Subjects With Systemic Lupus Erythematosus

International trial to evaluate the biological activity and safety of cenerimod (ACT-334441) in systemic lupus erythematosus (SLE) patients.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Cenerimod; Drug: Matching placebo

Detailed Description

This multicentre, double-blind, placebo-controlled study will have a staggered approach (Part A and B).

In part A, eligible patients will be randomly assigned (1:1:1:1) to once daily oral administration of cenerimod (0.5, 1, 2 mg) or placebo. After all patients have completed 4 weeks of treatment during part A, an Independent Data Monitoring Committee will review non-blinded data in an interim analysis to evaluate the safety profile of cenerimod and recommend whether the study could proceed to part B.

In part B, additional patients will be randomized (3:1) to once daily oral administration of cenerimod 4 mg or placebo.

All participants will receive study medication for 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus, 220116
    • Investigator Site
  • Minsk, Belarus, 223041
    • Investigator Site
  • Vitebsk, Belarus, 210037
    • Investigator Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Investigator Site
  • Plovdiv, Bulgaria, 4002
    • Investigator Site
  • Sofia, Bulgaria, 1612
    • Investigator Site
• Georgia
  • Tbilisi, Georgia, 0186
    • Investigator Site
• Russia
  • Kemerovo, Russia, 650066
    • Investigator Site
  • Kursk, Russia, 305007
    • Investigator Site
  • Omsk, Russia, 644111
    • Investigator Site
  • Orenburg, Russia, 460018
    • Investigator Site
  • Smolensk, Russia, 214025
    • Investigator Site
  • Vladimir, Russia, 600023
    • Investigator Site
• Ukraine
  • Vinnytsia, Ukraine, 21018
    • Investigator Site
  • Vinnytsia, Ukraine, 21029
    • Investigator Site
  • Zaporizhia, Ukraine, 69600
    • Investigator Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Investigator Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female participants aged 18 to 65 years with established SLE. Participants must have active SLE, Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score of at least 2 points for musculoskeletal or mucocutaneous manifestations and history or presence at screening of positive anti-nuclear antibodies (ANA) or anti-double-stranded DNA (anti-dsDNA) antibodies.
• Enrolled participants must be treated with background SLE medications.

Exclusion Criteria:

• Participants with significant medical conditions or therapies for such conditions (e.g., cardiovascular, pulmonary, immunological, hepatic, ophthalmological, infection and infection risks, history or presence of malignancy, history or presence of bone marrow or solid organ transplantation) or lactating or pregnant women.
• Participants with severe SLE disease or with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cenerimod 0.5 mg (Part A); Participants will receive cenerimod 0.5 mg capsules orally once daily for 12 weeks.	Drug: Cenerimod; One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).; Other Names: ACT-334441
Experimental: Cenerimod 1 mg (Part A); Participants will receive cenerimod 1 mg capsules orally once daily for 12 weeks.	Drug: Cenerimod; One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).; Other Names: ACT-334441
Experimental: Cenerimod 2 mg (Part A); Participants will receive cenerimod 2 mg capsules orally once daily for 12 weeks.	Drug: Cenerimod; One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).; Other Names: ACT-334441
Experimental: Cenerimod 4 mg (Part B); Participants will received cenerimod 4 mg capsules orally once daily for 12 weeks. This treatment arm will start after all patients in Part A have completed 4 weeks of placebo, 0.5 mg, 1 mg and 2 mg cenerimod treatment.	Drug: Cenerimod; One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).; Other Names: ACT-334441
Placebo Comparator: Matching placebo (Part A and B); Capsules of matching placebo taken orally once daily for 12 weeks.	Drug: Matching placebo; One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT)	The primary objective of the clinical study was to asses whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at end-of-treatment (EOT) minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12.	Baseline to end-of-treatment (EOT) (up to 12 weeks)
Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment	The primary objective of the clinical study was to assess whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at visit minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12.	Baseline, Week 2, Week 4, Week 8, Week 12, end-of-treatment Visit (up to 12 weeks)

Collaborators and Investigators

• Sponsor: Viatris Innovation GmbH
• Investigators: Study Director: Clinical Trials, Viatris Innovation GmbH

Publications and helpful links

General Publications

• Hermann V, Batalov A, Smakotina S, Juif PE, Cornelisse P. First use of cenerimod, a selective S1P1 receptor modulator, for the treatment of SLE: a double-blind, randomised, placebo-controlled, proof-of-concept study. Lupus Sci Med. 2019 Nov 9;6(1):e000354. doi: 10.1136/lupus-2019-000354. eCollection 2019.

Helpful Links

• Lay summary on results reference by Hermann V et al. First use of cenerimod, a selective S1P(1) receptor modulator, for the treatment of SLE: a double-blind, randomised, placebo-controlled, proof-of-concept study. Lupus Sci Med. 2019 Nov 9;6(1):e000354.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): January 23, 2017
• Study Completion (Actual): February 28, 2017

Study Registration Dates

• First Submitted: May 14, 2015
• First Submitted That Met QC Criteria: June 12, 2015
• First Posted (Estimated): June 16, 2015

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Systemic lupus erythematosus
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; cenerimod
• Other Study ID Numbers: AC-064A201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO