Efficacy and Safety of Afimetoran Compared with Placebo in Participants with Active Systemic Lupus Erythematosus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol-Myers Squibb Services Unlimited Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

25 Nov 2021 → ongoing

Decision date (initial)

2023-09-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bristol-Myers Squibb International Corporation

External identifiers

EU CT number

2023-504320-25-00

EudraCT number

2019-004021-25

WHO UTN

U1111-1241-6528

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Pharmacogenetic, Others, Efficacy, Pharmacodynamic, Safety

To assess the efficacy of Afimetoran versus placebo using a composite measure of improvement in lupus activity that is primarily driven by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), in participants with active SLE

Secondary objectives 5

1. To assess the efficacy of Afimetoran versus placebo using an alternative composite measure of improvement in lupus activity that is primarily driven by the British Isles Lupus Assessment Group (BILAG), in participants in active SLE
2. To assess the efficacy of Afimetoran versus placebo on measures of global and organ-specific clinical response in participants with active SLE
3. To assess the steroid-sparing effect of Afimetoran versus placebo in participants with active SLE
4. To characterize patient-reported health status in participants with active SLE on Afimetoran
5. To assess the safety and tolerability of Afimetoran versus placebo in participants with active SLE

Conditions and MedDRA coding

Active Systemic Lupus Erythematosus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Diagnosed ≥ 12 weeks before the screening visit and qualify as having Systemic Lupus Erythematosus (SLE), according to the SLE International Collaborating Clinics (SLICC) Classification Criteria at the screening visit
2. Test positive, as determined by the central laboratory, for at least one of the following lupus related autoantibodies at the time of screening: antinuclear antibody>/= 1:80, anti-double-stranded deoxyribonucleic acid (dsDNA) antibody, or anti-Smith antibody
3. Have a total Hybrid Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥ 6 points and clinical Hybrid SLEDAI score ≥ 4 points with joint involvement and/or rash
4. Inclusion criteria for long-term extension (LTE) period: - Completion of study treatment through Week 48 - In the opinion of the investigator, participant may benefit from continuation in the optional LTE period

Exclusion criteria 5

1. Active severe lupus nephritis (LN) as assessed by the investigator
2. Active or unstable neuropsychiatric lupus manifestations defined by the Hybrid SLEDAI
3. Diagnosis of Mixed Connective Tissue Disease for which the predominant diagnosis is not SLE
4. Antiphospholipid Syndrome
5. Exclusion criteria for long-term extension (LTE) period: - Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic, psychiatric) or active infection/infectious illness that, as determined by the investigator's clinical judgment, will substantially increase the risk to the participant if he or she participates in the LTE

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants who achieve an SLE Responder Index 4 (SRI[4]) response at Week 48

Secondary endpoints 22

1. Proportion of participants that achieve a British Isles Lupus Assessment Group (BILAG)-based Combine Lupus Assessment (BICLA) at Week 24 and Week 48
2. Proportion of participants who achieve an SRI(4) response at Week 24
3. Proportion of participants who achieve a Lupus Low Disease Activity State (LLDAS) response at Week 24 and Week 48
4. Proportion of participants with a Cutaneous Lupus Erythematosus Disease Area and Severity Index; Activity (CLASI-A) score ≥ 10 at baseline who achieve a decrease of ≥ 50% from baseline CLASI-A score (CLASI-50) response at Week 24 and Week 48
5. Proportion of participants with 6 or more swollen joints and 6 or more tender joints at baseline who achieve a ≥ 50% reduction from baseline in both swollen and tender joints at Week 24 and Week 48
6. Mean change from baseline in swollen joint count using the 28-joint count at Week 24 and Week 48 in participants with ≥ 2 swollen joints at baseline
7. Mean change from baseline in tender joint count at Week 24 and Week 48 using the 28- joint count in participants with ≥ 2 tender joints at baseline
8. Change from baseline in PGA score of disease activity at Week 24 and Week 48
9. Proportion of participants who achieve CS reduction or maintenance to ≤ 7.5 mg per day at Week 48
10. Change in patient reported disease activity from baseline to Week 24 and Week 48 according to the (36-item Short Form Health Questionnaire) SF-36
11. Number of participants that experience Serious Adverse Events (SAEs)
12. Proportion of participants that experience SAEs
13. Number of participants that experience Adverse Events (AEs)
14. Proportion of participants that experience AEs
15. Number of participants that experience abnormalities or clinically important changes in clinical laboratory values (Hematology tests; Chemistry tests, Coagulation tests, Urinalysis tests, Serology tests)
16. Proportion of participants that experience abnormalities or clinically important changes in clinical laboratory values (Hematology tests; Chemistry tests, Coagulation tests, Urinalysis tests, Serology tests)
17. Number of participants that experience abnormalities or clinically important changes in physical examination
18. Proportion of participants that experience abnormalities or clinically important changes in physical examination
19. Number of participants that experience abnormalities or clinically important changes in vital signs (body temperature, Respiratory rate, Blood pressure, Heart rate)
20. Proportion of participants that experience abnormalities or clinically important changes in vital signs (body temperature, Respiratory rate, Blood pressure, Heart rate)
21. Number of participants that experience abnormalities or clinically important changes in Electrocardiogram (ECG) parameters (PR Interval, QRS, QT interval, QtCF)
22. Proportion of participants that experience abnormalities or clinically important changes in ECG parameters (PR Interval, QRS, QT interval, QtCF)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol-Myers Squibb Services Unlimited Company

Sponsor organisation

Bristol-Myers Squibb Services Unlimited Company

Address

Plaza 254, Blanchardstown Corporate Park 2 Blanchardstown Corporate Park 2

City

Dublin 15

Postcode

D15 T867

Country

Ireland

Scientific contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Public contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Third parties 12

Locations

6 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications