NCT02696785: COAST-V

A Study of Ixekizumab (LY2439821) in bDMARD-Naive Participants With Radiographic Axial Spondyloarthritis

Completed Phase 3 Results posted Last updated 19 November 2019

What this trial tests

Phase 3 trial testing Ixekizumab in Spondyloarthritis in 341 participants. Completed in 17 October 2018.

Timeline

2 May 2016

Primary endpoint
8 December 2017

17 October 2018

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	341
Start date	2 May 2016
Primary completion	8 December 2017
Estimated completion	17 October 2018
Sites	28 locations across Netherlands, Japan, Taiwan, Germany, South Korea, United States, Czechia

Drugs / interventions tested

• Ixekizumab (ixekizumab) — full drug profile →
• Placebo
• Adalimumab (ADALIMUMAB) — full drug profile →

Conditions studied

• Spondyloarthritis — all drugs for Spondyloarthritis →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Spondyloarthritis. 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.

Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response Primary · Week 16

ASAS40 is defined as improvement from baseline of greater than or equal to (\>=) 40% and absolute improvement from baseline of at least 2 units in at least 3 of the following 4 domains without any worsening in the remaining domains. 1. Patient Global: How active was your spondylitis on average during the last week? score range 0 (not active) to 10 (very active). 2. Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3. Bath Ankylosing Spondylitis Functional Index: Participant is asked to rate the difficulty associated with 10 i

Group	Value	95% CI
Placebo	18.4
Adalimumab	35.6
IXE80Q4W	48.1
IXE80Q2W	51.8

Percentage of Participants Achieving an ASAS20 Response Secondary · Week 16

ASAS20 response is defined as a ≥20% improvement and an absolute improvement from baseline of ≥1 units in ≥3 of 4 following domains and no worsening of ≥20% and ≥1 unit (range 0 to 10) in the remaining domain. 1. Patient Global: How active was your spondylitis on average during the last week? score range 0 (not active) to 10 (very active). 2. Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3. Bath Ankylosing Spondylitis Functional Index: Participant is asked to rate the difficulty associated with 10 individual basic functio

Group	Value	95% CI
Placebo	40.2
Adalimumab 40mg	58.9
IXE80Q4W	64.2
IXE80Q2W	68.7

Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) Secondary · Baseline, Week 16

ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with CRP as acute phase reactant) are the following: 1. Total back pain 2. Patient global 3. Peripheral pain/swelling 4. Duration of morning stiffness 5. CRP in mg/L The ASDAScrp is calculated with the following equation: 0.121 × total back pain + 0.110 × patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in mg/liter, the range of other variables is from 0 to 10.Data from five variables combined to yield a score (0.6361 to no define

Group	Value	95% CI
Placebo	-0.46	± 0.099
Adalimumab 40mg	-1.30	± 0.096
IXE80Q4W	-1.43	± 0.102
IXE80Q2W	-1.37	± 0.101

Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) Response Secondary · Week 16

The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to radiographic axial spondyloarthritis measuring discomfort, pain, and fatigue. 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. participants need to score each item with a score from 0 to 10 (NRS). total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem). BASDAI50 represents an improvement of ≥50% of the BASDAI score from baseline.

Group	Value	95% CI
Placebo	17.2
Adalimumab 40mg	32.2
IXE80Q4W	42.0
IXE80Q2W	43.4

Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Secondary · Baseline, Week 16

The BASFI is a participant-reported assessment that establishes a participants functional baseline and subsequent response to treatment. To complete the BASFI, a participant is asked to rate the difficulty associated with 10 individual basic functional activities. Participants respond to each question using an NRS scale (range 0 to 10) with a higher score indicating worse function. The participants final BASFI score is the mean of the 10 item scores has a possible minimum value of 0 and a possible maximum value of 10, with a higher score indicating worse function. LSMean was calculated using

Group	Value	95% CI
Placebo	-1.16	± 0.215
Adalimumab 40mg	-2.14	± 0.209
IXE80Q4W	-2.39	± 0.222
IXE80Q2W	-2.43	± 0.219

Percentage of Participants Achieving ASDAS Inactive Disease Secondary · Week 16

ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with CRP as acute phase reactant) are the following: 1. Total back pain 2. Patient global 3. Peripheral pain/swelling 4. Duration of morning stiffness 5. CRP in mg/L The ASDAScrp is calculated with the following equation: 0.121 × total back pain + 0.110 × patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in mg/liter, the range of other variables is from 0 to 10.Data from five variables combined to yield a score (0.6361 to no define

Group	Value	95% CI
Placebo	2.3
Adalimumab 40mg	15.6
IXE80Q4W	16.0
IXE80Q2W	10.8

Change From Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Ankylosing Spondylitis Spinal Magnetic Resonance Imaging [ASSpiMRI] - Berlin Score) Secondary · Baseline, Week 16

The Berlin modification of Ankylosing Spondylitis spine MRI score for activity (ASspiMRI) scoring technique assesses inflammation in each of 23 disco-vertebral units (DVU). All 23 disco-vertebral units (DVU) of the spine (from C2 to S1) are scored for bone marrow edema. Scores for each DVU range from 0-3 (0=normal; 1=minor bone marrow edema \[less than or equal to 25% of DVU; 3=severe bone marrow edema (more that 50% of DVU)\]. The composite score ranges from 0 to 69, with higher scores reflecting worse disease. Least Squares (LS) Mean was calculated using ANCOVA model with treatment, geograp

Group	Value	95% CI
Placebo	-0.15	± 0.323
Adalimumab 40mg	-2.92	± 0.314
IXE80Q4W	-2.77	± 0.328
IXE80Q2W	-2.54	± 0.330

Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores Secondary · Baseline, Week 16

The SF-36 is a 36-item participant administered measure designed to be a short, multipurpose assessment of health in the areas of physical functioning, role - physical, role - emotional, bodily pain, vitality, social functioning, mental health, and general health. The 2 overarching domains of mental well- being and physical well-being are captured by the Mental Component Summary and Physical Component Summary scores. T-scores are used for analysis. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LSMean was calculated using

PCS

Group	Value	95% CI
Placebo	3.6432	± 0.7530
Adalimumab 40mg	6.9005	± 0.7310
IXE80Q4W	7.6952	± 0.7768
IXE80Q2W	7.9686	± 0.7665

MCS

Group	Value	95% CI
Placebo	2.1229	± 0.8431
Adalimumab 40mg	2.5550	± 0.8225
IXE80Q4W	2.7502	± 0.8763
IXE80Q2W	2.5696	± 0.8650

Change From Baseline in ASAS Health Index (ASAS HI) Secondary · Baseline, Week 16

ASAS HI is a disease-specific health-index instrument designed to assess the impact of interventions for SpA, including axSpA. The 17-item instrument has scores ranging from 0 (good health) to 17 (poor health). Each item consists of one question that the participant needs to respond to with either "I agree" (score of 1) or "I do not agree" (score of 0). A score of "1" is given where the item is affirmed, indicating adverse health. All item scores are summed to give a total score or index. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, baseline v

Group	Value	95% CI
Placebo	-1.25	± 0.300
Adalimumab 40mg	-2.30	± 0.292
IXE80Q4W	-2.36	± 0.311
IXE80Q2W	-2.74	± 0.306

Change From Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP) Secondary · Baseline, Week 16

High sensitivity CRP is the measure of acute phase reactant. It will be measured with a high sensitivity assay at the central laboratory to help assess the effect of Ixekizumab on disease activity. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, visit and treatment-by-visit interaction as fixed factors.

Group	Value	95% CI
Placebo	1.426	± 1.9244
Adalimumab 40mg	-7.202	± 1.8688
IXE80Q4W	-5.209	± 1.9803
IXE80Q2W	-6.565	± 1.9582

Change From Baseline in Mobility on the Bath Ankylosing Spondylitis Metrology Index (BASMI) Secondary · Baseline, Week 16

The BASMI is a combined index comprising the following 5 clinical measurements of spinal mobility in participants with rad-axSpA. 1. Lateral spinal flexion 2. Tragus-to-wall distance 3. Lumbar flexion (modified Schrober) 4. Maximal intermalleolar distance 5. Cervical rotation. The BASMI includes these 5 measurements that are each scaled to a score of 0 to 10 depending on the result of the assessment (BASMI linear function). The average score of the 5 assessments gives the BASMI linear result. The higher the BASMI score the more severe the participants limitation of movement due to their AS.

Group	Value	95% CI
Placebo	-0.080	± 0.0826
Adalimumab 40mg	-0.447	± 0.0800
IXE80Q4W	-0.502	± 0.0858
IXE80Q2W	-0.408	± 0.0840

Change From Baseline in Chest Expansion Secondary · Baseline, Week 16

While participants have their hands resting on or behind the head, the assessor has measured the chest's encircled length by centimeter at the fourth intercostal level anteriorly. The difference between maximal inspiration and expiration in centimeters was recorded. Two tries were recorded. The better measurement (larger difference) of 2 tries (in centimeters) was used for analyses. LSMean was calculated using MMRM model with treatment, geographic region, baseline CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

Group	Value	95% CI
Placebo	0.06	± 0.152
Adalimumab 40mg	0.70	± 0.148
IXE80Q4W	0.49	± 0.158
IXE80Q2W	0.67	± 0.155

Adverse events — posted to ClinicalTrials.gov

Time frame: Upto 76 Weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo - Blinded Treatment

Serious: 0/86 (0%)

Deaths: 0/86

Adalimumab 40mg - Blinded Treatment

Serious: 3/90 (3%)

Deaths: 0/90

IXE80Q2W - Blinded Treatment

Serious: 1/83 (1%)

Deaths: 0/83

IXE80Q4W - Blinded Treatment

Serious: 1/81 (1%)

Deaths: 0/81

ADA/PBO - Washout Treatment Period

Serious: 0/88 (0%)

Deaths: 0/88

PBO/IXE - Extended Treatment Period

Serious: 4/86 (5%)

Deaths: 0/86

ADA/PBO/IXE - Extended Treatment Period

Serious: 7/86 (8%)

Deaths: 0/86

IXE80Q2W/IXE80Q2W - Extended Treatment

Serious: 3/79 (4%)

Deaths: 0/79

IXE80Q4W/IXE80Q4W - Extended Treatment

Serious: 4/78 (5%)

Deaths: 0/78

PBO-follow-up Period

Serious: 0/1 (0%)

Deaths: 0/1

IXE80Q2W-follow-up Period

Serious: 0/24 (0%)

Deaths: 0/24

IXE80Q4W-follow-up Period

Serious: 0/16 (0%)

Deaths: 0/16

Serious adverse events (28 terms)

Reaction	System	Placebo - Blinded Treatment	Adalimumab 40mg - Blinded …	IXE80Q2W - Blinded Treatment	IXE80Q4W - Blinded Treatment	ADA/PBO - Washout Treatmen…	PBO/IXE - Extended Treatme…	ADA/PBO/IXE - Extended Tre…	IXE80Q2W/IXE80Q2W - Extend…	IXE80Q4W/IXE80Q4W - Extend…	PBO-follow-up Period	IXE80Q2W-follow-up Period	IXE80Q4W-follow-up Period
Lymphadenitis	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Atrioventricular block complete	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—
Crohn's disease	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Appendicitis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonia haemophilus	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Tonsillitis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Ankle fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—
Avulsion fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—
Cervical vertebral fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—
Post procedural haematoma	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—
Radius fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—
Road traffic accident	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—
Arthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—
Plica syndrome	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—
Parathyroid tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—
Cerebral haemorrhage	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Subarachnoid haemorrhage	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—

Other adverse events (11 terms — click to expand)

Reaction	System	Placebo - Blinded Treatment	Adalimumab 40mg - Blinded …	IXE80Q2W - Blinded Treatment	IXE80Q4W - Blinded Treatment	ADA/PBO - Washout Treatmen…	PBO/IXE - Extended Treatme…	ADA/PBO/IXE - Extended Tre…	IXE80Q2W/IXE80Q2W - Extend…	IXE80Q4W/IXE80Q4W - Extend…	PBO-follow-up Period	IXE80Q2W-follow-up Period	IXE80Q4W-follow-up Period
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Injection site reaction	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—
Ocular discomfort	Eye disorders	—	—	—	—	—	—	—	—	—	—	—	—
Vaginal infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—
Adnexal torsion	Reproductive system and breast disorders	—	—	—	—	—	—	—	—	—	—	—	—
Menopausal symptoms	Reproductive system and breast disorders	—	—	—	—	—	—	—	—	—	—	—	—
Menstruation irregular	Reproductive system and breast disorders	—	—	—	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Lymphadenitis, Atrioventricular block complete, Crohn's disease, Dyspepsia, Appendicitis, Cellulitis, Gastroenteritis, Pneumonia haemophilus.

Data from ClinicalTrials.gov NCT02696785 adverse events section.

Sponsor's own description

The main purpose of this study is to evaluate the safety and efficacy of the study drug known as ixekizumab in biological disease-modifying anti-rheumatic drugs (bDMARDs)-naive participants with radiographic axial spondyloarthritis (rad-axSpA).

Publications & conference data

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

1. Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders.
   Fasching P, Stradner M, Graninger W, Dejaco C, et al · · 2017 · cited 178× · PMID 28098832 · DOI 10.3390/molecules22010134
2. Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors.
   Deodhar A, Poddubnyy D, Pacheco-Tena C, Salvarani C, et al · · 2019 · cited 158× · PMID 30343531 · DOI 10.1002/art.40753
3. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W).
   Dougados M, Wei JC, Landewé R, Sieper J, et al · · 2020 · cited 97× · PMID 31685553 · DOI 10.1136/annrheumdis-2019-216118
4. Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective.
   Zwicky P, Unger S, Becher B. · · 2020 · cited 66× · PMID 31727781 · DOI 10.1084/jem.20191123
5. Mechanistic rationales for targeting interleukin-17A in spondyloarthritis.
   Raychaudhuri SP, Raychaudhuri SK. · · 2017 · cited 54× · PMID 28270233 · DOI 10.1186/s13075-017-1249-5
6. Targeting inflammatory pathways in axial spondyloarthritis.
   Furst DE, Louie JS. · · 2019 · cited 34× · PMID 31164157 · DOI 10.1186/s13075-019-1885-z
7. Spinal Radiographic Progression and Predictors of Progression in Patients With Radiographic Axial Spondyloarthritis Receiving Ixekizumab Over 2 Years.
   van der Heijde D, Østergaard M, Reveille JD, Baraliakos X, et al · · 2022 · cited 25× · PMID 34853086 · DOI 10.3899/jrheum.210471
8. Continuing versus withdrawing ixekizumab treatment in patients with axial spondyloarthritis who achieved remission: efficacy and safety results from a placebo-controlled, randomised withdrawal study (COAST-Y).
   Landewé RB, Gensler LS, Poddubnyy D, Rahman P, et al · · 2021 · cited 23× · PMID 33958326 · DOI 10.1136/annrheumdis-2020-219717