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

Systemic Lupus Erythematosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02472795
• Other study ID #: AC-064A201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 1, 2015
• Est. completion date: February 28, 2017

Study information

• Verified date: February 2020
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: February 28, 2017
• Est. primary completion date: January 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

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).
• 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).

Locations

Country	Name	City	State
Belarus	Investigator Site	Minsk
Belarus	Investigator Site	Minsk
Belarus	Investigator Site	Vitebsk
Bulgaria	Investigator Site	Plovdiv
Bulgaria	Investigator Site	Plovdiv
Bulgaria	Investigator Site	Sofia
Georgia	Investigator Site	Tbilisi
Russian Federation	Investigator Site	Kemerovo
Russian Federation	Investigator Site	Kursk
Russian Federation	Investigator Site	Omsk
Russian Federation	Investigator Site	Orenburg
Russian Federation	Investigator Site	Smolensk
Russian Federation	Investigator Site	Vladimir
Ukraine	Investigator Site	Vinnytsya
Ukraine	Investigator Site	Vinnytsya
Ukraine	Investigator Site	Zaporizhia
United States	Investigator Site	Anniston	Alabama
United States	Investigator Site	Clearwater	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Countries where clinical trial is conducted

United States,  Belarus,  Bulgaria,  Georgia,  Russian Federation,  Ukraine, 

References & Publications (1)

Hermann V, Batalov A, Smakotina S, Juif PE, Cornelisse P. 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):e0003 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)

External 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.