Last reviewed · How we verify

NCT02334306

A Phase 2a, Randomized, Placebo Controlled, Study to Evaluate the Safety and Efficacy of AMG 557/MEDI5872 in Primary Sjögren's Syndrome

Completed Phase 2 Results posted Last updated 19 March 2019
What this trial tests

Phase 2 trial testing AMG 557/MEDI5872 in Primary Sjögren's Syndrome in 32 participants. Completed in 13 August 2018.

Timeline
8 June 2015
Primary endpoint
16 January 2018
13 August 2018

Quick facts

Lead sponsorMedImmune LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment32
Start date8 June 2015
Primary completion16 January 2018
Estimated completion13 August 2018
Sites13 locations across France, United Kingdom, United States, Sweden

Drugs / interventions tested

Conditions studied

Sponsor

MedImmune LLC — full company profile →

Who can join

Adults 18 to 75, any sex, with Primary Sjögren's Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99 Primary · Baseline (Day 1 predose) and Day 99

The European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological). Each domain is assessed for activity level in 3 or 4 levels (i.e., no, low, moderate, high) according to their severity (no disease activity equals to 0 and for high disease activity the

GroupValue95% CI
Placebo-2.3± 0.8
MEDI5872 210 mg-3.8± 0.9
Ratio to Baseline in Peripheral Blood Biomarkers at Day 99 Secondary · Baseline (Day 1 predose) and Day 99

The peripheral blood biomarkers included total plasma cell levels (including plasma blast levels) and T follicular helper (TFH) cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented.

Plasma Cell Levels
GroupValue95% CI
Placebo0.70± 0.24
MEDI5872 210 mg0.65± 0.24
TFH Cells
GroupValue95% CI
Placebo0.94± 0.27
MEDI5872 210 mg0.62± 0.27
Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99 Secondary · Baseline (Day 1 predose) and Day 99

The minor salivary gland biopsy biomarkers included total plasma cell levels, CD4/ inducible T-cell costimulator (ICOS) TFH cells, and PD-1/ICOS TFH cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented.

Total Plasma Cells
GroupValue95% CI
Placebo1.32± 0.13
MEDI5872 210 mg1.15± 0.11
CD4/ICOS TFH Cells
GroupValue95% CI
Placebo1.76± 0.21
MEDI5872 210 mg0.75± 0.18
PD-1/ICOS TFH Cells
GroupValue95% CI
Placebo1.06± 0.19
MEDI5872 210 mg1.07± 0.16
Ratio to Baseline in Focus Score at Day 99 Secondary · Baseline (Day 1 predose) and Day 99

The focus score is a semi-quantitative assessment of focal lymphocytic sialoadenitis, which is defined as the presence of \>= 1 dense aggregate of 50 or more lymphocytes in a 4 mm2 area. Higher numbers are associated with more inflammation.

GroupValue95% CI
Placebo0.79± 0.53
MEDI5872 210 mg0.96± 0.50
Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) Score at Day 99 Secondary · Baseline (Day 1 predose) and Day 99

The European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) is a patient-reported, subjective symptom index for primary Sjögren's syndrome. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Adjusted mean change and standard error are presented.

GroupValue95% CI
Placebo-1.0± 0.5
MEDI5872 210 mg-0.6± 0.5
Percentage of ESSDAI Responders at Day 99 Secondary · Baseline (Day 1 predose) and Day 99

The ESSDAI is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological). Each domain is assessed for activity level in 3 or 4 levels (no, low, moderate, high) according to their severity (0=no disease activity and ¾ = high disease activity of the domain). Each domain is assigned a weight between 1 and 6, and the domain score is multipli

ESSDAI [3]
GroupValue95% CI
Placebo18.8
MEDI5872 210 mg43.8
ESSDAI [4]
GroupValue95% CI
Placebo18.8
MEDI5872 210 mg43.8
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Secondary · Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were collected from Day 1 (postdose) until Day 99 for 'Placebo' arm and Day 296 for 'Any MEDI5872 210 mg' arm that were

Any TEAEs
GroupValue95% CI
Placebo14
Any MEDI5872 210 mg29
Any TESAEs
GroupValue95% CI
Placebo0
Any MEDI5872 210 mg1
Number of Participants With Adverse Events of Special Interest (AESIs) Secondary · Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period

An AESI (serious or non-serious) was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor. The AESIs for this study were hepatic function abnormality meeting the definition of Hy's law, new or reactivated tuberculosis infection, malignancy, and hypersensitivity and anaphylactic reactions. Treatment-emergent AESIs were collected from Day 1 (postdose) until Day 99 for 'Placebo' arm and Day 296 for 'Any MEDI5872 210 mg' arm.

GroupValue95% CI
Placebo1
Any MEDI5872 210 mg6

Adverse events — posted to ClinicalTrials.gov

Time frame: Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period 1 participant from 'Placebo' arm discontinued treatment before Day 99, didn't receive MEDI5872 dose and entered in safety follow-up period.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 0/16 (0%)
Deaths: 0/16
Any MEDI5872 210 mg
Serious: 1/31 (3%)
Deaths: 0/31

Serious adverse events (1 terms)

ReactionSystemPlaceboAny MEDI5872 210 mg
Small intestine polypGastrointestinal disorders
Other adverse events (132 terms — click to expand)

ReactionSystemPlaceboAny MEDI5872 210 mg
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Injection site rashGeneral disorders
Urinary tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Dental cariesGastrointestinal disorders
NauseaGastrointestinal disorders
Injection site painGeneral disorders
Oral herpesInfections and infestations
Sjogren's syndromeMusculoskeletal and connective tissue disorders
ErythemaSkin and subcutaneous tissue disorders
PalpitationsCardiac disorders
Mouth ulcerationGastrointestinal disorders
FatigueGeneral disorders
Injection site bruisingGeneral disorders
Injection site erythemaGeneral disorders
ConjunctivitisInfections and infestations
Gastroenteritis viralInfections and infestations
Lower respiratory tract infectionInfections and infestations
ParonychiaInfections and infestations
Viral upper respiratory tract infectionInfections and infestations
Muscle spasmsMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
AlopeciaSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
HaematomaVascular disorders
AnaemiaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
VertigoEar and labyrinth disorders
Vision blurredEye disorders
Abdominal pain upperGastrointestinal disorders
Aphthous ulcerGastrointestinal disorders

Most-reported serious reactions: Small intestine polyp.

Data from ClinicalTrials.gov NCT02334306 adverse events section.

Sponsor's own description

A Phase 2a study to evaluate the efficacy and safety of AMG 557/MEDI5872 in Primary Sjögren's Syndrome

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.
    Pontarini E, Murray-Brown WJ, Croia C, Lucchesi D, et al · · 2020 · cited 128× · PMID 32963045 · DOI 10.1136/annrheumdis-2020-217646
  2. Current State of Knowledge on Primary Sjögren's Syndrome, an Autoimmune Exocrinopathy.
    Parisis D, Chivasso C, Perret J, Soyfoo MS, et al · · 2020 · cited 114× · PMID 32698400 · DOI 10.3390/jcm9072299
  3. Innate Immunity and Biological Therapies for the Treatment of Sjögren's Syndrome.
    Srivastava A, Makarenkova HP. · · 2020 · cited 40× · PMID 33271951 · DOI 10.3390/ijms21239172
  4. Acazicolcept (ALPN-101), a dual ICOS/CD28 antagonist, demonstrates efficacy in systemic sclerosis preclinical mouse models.
    Orvain C, Cauvet A, Prudent A, Guignabert C, et al · · 2022 · cited 21× · PMID 34986869 · DOI 10.1186/s13075-021-02709-2
  5. Biological Therapy in Primary Sjögren's Syndrome: Effect on Salivary Gland Function and Inflammation.
    Chowdhury F, Tappuni A, Bombardieri M. · · 2021 · cited 13× · PMID 34336905 · DOI 10.3389/fmed.2021.707104
  6. The Future of Targeted Treatment of Primary Sjögren's Syndrome: A Focus on Extra-Glandular Pathology.
    Zeng W, Zhou X, Yu S, Liu R, et al · · 2022 · cited 12× · PMID 36430611 · DOI 10.3390/ijms232214135
  7. Emerging treatment for Sjögren's disease: a review of recent phase II and III trials.
    Fox RI, Fox CM, McCoy SS. · · 2023 · cited 9× · PMID 37127914 · DOI 10.1080/14728214.2023.2209720
  8. The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia.
    Külp M, Siemund AL, Larghero P, Dietz A, et al · · 2022 · cited 8× · PMID 35800767 · DOI 10.1016/j.isci.2022.104613

Verify or expand the search:

Other MedImmune LLC trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02334306.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing