Last reviewed · How we verify

NCT03765788: TitAIN

A Placebo-controlled Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab in Giant Cell Arteritis

Completed Phase 2 Results posted Last updated 21 August 2023
What this trial tests

Phase 2 trial testing Secukinumab 300 mg, s.c. in Giant Cell Arteritis in 52 participants. Completed in 8 June 2021.

Timeline
30 January 2019
Primary endpoint
8 June 2021
8 June 2021

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment52
Start date30 January 2019
Primary completion8 June 2021
Estimated completion8 June 2021
Sites11 locations across Germany

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

50 and older, any sex, with Giant Cell Arteritis. 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 in Sustained Remission Until Week 28 Primary · Until week 28

Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper regimen. Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of Giant Cell Arteritis (GCA) and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) and/or C-reactive Protein (CRP) (\>/=10.0 mg/L) attributable to GCA. Patients were classified as non-responders if they did not achieve remission within 12 weeks of Basel

GroupValue95% CI
Secukinumab19
Placebo6
Percentage of Participants in Remission at Week 12 Secondary · Week 12

Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper Regimen. Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) and/or CRP (\>/=10.0 mg/L) attributable to GCA. Patients were classified as non-responders if they did not achieve remission within 12 weeks of Baseline (remission referred to the absence of fl

GroupValue95% CI
Secukinumab22
Placebo12
Time to First GCA Flare After Clinical Remission Secondary · Up to Week 52 (included)

Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) and/or CRP (\>/=10.0 mg/L) attributable to GCA. Time to first flare after remission referred to time from first day of study treatment until first post-Baseline flare. For time to first GCA flare after remission (up to and including Week 52), patients who prematurely discontinued study treatment prior to Week 52 were censored at the time of premature discontinuation and

GroupValue95% CI
SecukinumabNANA – NA
Placebo197.0101.0 – 280.0
Total Cumulative Prednisolone Dose Over 28 Weeks and 52 Weeks Secondary · from Baseline to week 28, from baseline to week 52 weeks

Total cumulative co-administered prednisolone treatment was summarized over time by treatment arm. Patients received a daily dose of prednisolone, which was decreased (i.e. tapered down) from Baseline to Week 26. No additional prednisolone or equivalent was permitted.

Baseline to Week 28
GroupValue95% CI
Secukinumab2689.70± 935.860
Placebo2693.74± 1241.907
Baseline to Week 52
GroupValue95% CI
Secukinumab2841.26± 1116.192
Placebo3375.58± 1720.978
Percentage of Participants With GCA Who Had Sustained Remission Until Week 52 Secondary · Until Week 52

Remission was defined as the absence of flare. Sustained remission was defined as patients without flare until Week 52 and in adherence to the protocol prednisolone taper regimen plus prednisolone-free phase from Week 27 onwards. Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) and/or CRP (\>/=10.0 mg/L) attributable to GCA. Patients were classified as non-responders if they did not achieve remission within 12 weeks o

GroupValue95% CI
Secukinumab16
Placebo2
Number of Participants on Prednisolone Dose ≤ 5mg/Day Secondary · Week 19, Week 28, Week 52

Number of participants on co-administered prednisolone treatment ≤ 5mg/day who responded at Week 19, Week 26 and Week 52. Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper Regimen. There were 2 taper regimens: for patients on 40 to 60 mg/day prednisolone at Baseline and for patients on 25 to 40 mg/day prednisolone at Baseline depending on patients' prednisolone levels at Baseline. Prednisolone was tapered from a dose of 25 mg to 60 mg at Baseline to 1 mg at Week 26 \[last dos

Week 19 (n = 25, 20)
GroupValue95% CI
Secukinumab22
Placebo10
Week 28 (n = 23, 20)
GroupValue95% CI
Secukinumab19
Placebo9
Week 52 (n = 21, 17)
GroupValue95% CI
Secukinumab19
Placebo13
Physicians Global Assessment (PhGA) of Disease Activity: Change From Baseline Score Via Visual Analogue Scale (VAS) Secondary · Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52

Clinician Reported Outcome: Physicians global assessment (PhGA) using a visual analogue scale (VAS) scale. VAS is a range of scores from 0-100, with lower change from baseline scores indicating a more favorable outcome and higher change from baseline scores indicating a greater disease activity.

Week 4 (n = 27, 23)
GroupValue95% CI
Secukinumab-4.8± 14.43
Placebo-3.2± 18.45
Week 8 (n = 26, 21)
GroupValue95% CI
Secukinumab-5.8± 12.77
Placebo2.1± 18.94
Week 12 (n = 25, 20)
GroupValue95% CI
Secukinumab-3.4± 21.93
Placebo-3.1± 10.81
Week 16 (n = 25, 20)
GroupValue95% CI
Secukinumab-4.1± 15.62
Placebo0.7± 13.97
Week 20 (n = 24, 20)
GroupValue95% CI
Secukinumab-6.9± 14.78
Placebo-1.5± 14.32
Week 24 (n = 23, 20)
GroupValue95% CI
Secukinumab-4.3± 15.92
Placebo2.2± 17.22
Week 28 (23, 19)
GroupValue95% CI
Secukinumab-5.4± 15.61
Placebo3.9± 21.47
Week 36 (21, 19)
GroupValue95% CI
Secukinumab-8.7± 18.45
Placebo0.7± 17.45
Patients Global Assessment (PGA) of Disease Activity: Change From Baseline Via Visual Analogue Scale (VAS) Secondary · Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52

Patient Reported Outcome: Patients global assessment (PGA) score using a VAS scale. VAS is a range of scores from 0-100, with lower change from baseline scores indicating a more favorable outcome and higher change from baseline scores indicating a greater disease activity.

Week 4 (n = 27, 23)
GroupValue95% CI
Secukinumab-15.8± 28.17
Placebo-0.5± 23.58
Week 8 (n = 26, 21)
GroupValue95% CI
Secukinumab-15.8± 27.61
Placebo-10.8± 27.64
Week 12 (n = 25, 20)
GroupValue95% CI
Secukinumab-8.0± 29.43
Placebo-11.9± 31.46
Week 16 (n = 25, 20)
GroupValue95% CI
Secukinumab-18.6± 19.39
Placebo-8.8± 31.43
Week 20 (n = 24, 20)
GroupValue95% CI
Secukinumab-19.18± 30.68
Placebo-6.9± 31.94
Week 24 (n = 23, 20)
GroupValue95% CI
Secukinumab-14.9± 28.84
Placebo-7.0± 30.61
Week 28 (n = 23, 19)
GroupValue95% CI
Secukinumab-14.4± 25.46
Placebo-8.0± 31.31
Week 36 (n = 21, 19)
GroupValue95% CI
Secukinumab-20.9± 22.31
Placebo-8.6± 29.90
Change From Baseline in FACIT-Fatigue Scale Secondary · Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52

Patient Reported Outcome: Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue is a 13-item questionnaire with a full scale of 0 -52 that assesses self-reported fatigue and its impact upon daily activities and function. The higher the score the better functioning (less fatigue).

Week 4 (n = 27, 23)
GroupValue95% CI
Secukinumab2.11± 9.613
Placebo-0.96± 7.358
Week 8 (n = 26, 21)
GroupValue95% CI
Secukinumab2.19± 10.190
Placebo0.81± 7.498
Week 12 (n = 25, 20)
GroupValue95% CI
Secukinumab0.96± 11.175
Placebo-0.25± 10.047
Week 16 (n = 25, 20)
GroupValue95% CI
Secukinumab2.12± 8.876
Placebo-0.36± 8.884
Week 20 (n =24, 20)
GroupValue95% CI
Secukinumab3.42± 8.617
Placebo0.05± 10.318
Week 24 (n = 23, 20)
GroupValue95% CI
Secukinumab2.91± 10.409
Placebo-3.10± 11.281
Week 28 (n = 23, 19)
GroupValue95% CI
Secukinumab3.61± 11.044
Placebo0.42± 9.203
Week 36 (n = 21, 19)
GroupValue95% CI
Secukinumab3.90± 7.245
Placebo1.84± 8.719
Change From Baseline in Short-Form (SF)-36 Questionnaire Secondary · Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52

Patient Reported Outcome: The SF-36 is a standardized questionnaire used to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. It consists of 8 subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. The higher the score (change from baseline) the more favorable the outcome. The values were reported by change from baseline in SF-36 domain scores.

Week 4: Physical Functioning (PF) (n = 27, 23)
GroupValue95% CI
Secukinumab0.14± 7.562
Placebo-1.25± 4.417
Week 8: PF (n = 26 ,21)
GroupValue95% CI
Secukinumab-0.44± 8.849
Placebo0.18± 4.987
Week 12: PF (n = 25, 20)
GroupValue95% CI
Secukinumab0.38± 6.322
Placebo-0.38± 8.750
Week 16: PF (n = 25, 20)
GroupValue95% CI
Secukinumab-0.00± 8.646
Placebo-0.86± 6.814
Week 20: PF (n = 24, 20)
GroupValue95% CI
Secukinumab0.80± 8.098
Placebo-0.10± 6.495
Week 24: PF (n = 22, 20)
GroupValue95% CI
Secukinumab0.52± 5.702
Placebo-2.11± 8.667
Week 28: PF (n = 23, 19)
GroupValue95% CI
Secukinumab1.25± 5.276
Placebo-0.40± 6.460
Week 36: PF (n = 21, 19)
GroupValue95% CI
Secukinumab1.37± 5.778
Placebo-1.31± 6.631
Change From Baseline in EQ-5D-5L (EuroQol 5D) Questionnaire Secondary · Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52

EQ-5D-5L, a self-administered questionnaire assessing health status in adults, is divided into 2 sections. The 1st section addresses 5 dimensions (mobility, self-care, usual activity, pain/discomfort, \& anxiety/depression). Items are rated either "no problem", "slight problems", "moderate problems", "severe problems", or "extreme problems/unable." A composite health index is defined by combining the levels for each dimension. The 2nd section measures self-rated (global) health status via vertically oriented VAS where 100 represents the "best possible health state" \& 0 represents the "worst p

EQ-5D-5L VAS: Week 4 (n = 27, 23)
GroupValue95% CI
Secukinumab11.26± 16.819
Placebo1.87± 21.467
EQ-5D-5L VAS: Week 8 (n = 26, 21)
GroupValue95% CI
Secukinumab5.58± 16.650
Placebo5.52± 29.646
EQ-5D-5L VAS: Week 12 (n = 25, 20)
GroupValue95% CI
Secukinumab4.64± 19.598
Placebo3.30± 22.850
EQ-5D-5L VAS: Week 16 (n = 25, 20)
GroupValue95% CI
Secukinumab7.000± 19.530
Placebo4.40± 27.354
EQ-5D-5L VAS: Week 20 (n = 24, 20)
GroupValue95% CI
Secukinumab7.88± 19.077
Placebo6.30± 25.041
EQ-5D-5L VAS: Week 24 (n = 23, 20)
GroupValue95% CI
Secukinumab5.39± 17.598
Placebo-1.00± 29.902
EQ-5D-5L VAS: Week 28 (n = 23, 19)
GroupValue95% CI
Secukinumab4.43± 17.840
Placebo10.37± 21.670
WEQ-5D-5L VAS: Week 36 (n = 21, 19)
GroupValue95% CI
Secukinumab6.90± 17.972
Placebo5.32± 28.825
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Secondary · Baseline, Week 28, Week 52

ESR is a laboratory test that provides a non-specific measure of inflammation. This was assessed in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.

Week 28 (n = 23, 18)
GroupValue95% CI
Secukinumab4.043± 16.1934
Placebo14.667± 23.9141
Week 52 (n = 21, 16)
GroupValue95% CI
Secukinumab-3.286± 10.6167
Placebo10.000± 14.8728

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were reported from first dose of study treatment and co-administered Prednisolone treatment until end of treatment (48 weeks) plus 4 weeks (52 weeks). The mean/standard deviation exposure to the study treatment was 49.5 (9.6) weeks for secukinumab and 46.9 (12.6) weeks for placebo. The mean/standard deviation exposure to the co-administered prednisolone treatment was 307 (9.6) weeks for secukinumab and 43.2 (12.2) weeks for placebo.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Secukinumab
Serious: 6/27 (22%)
Deaths: 1/27
Placebo
Serious: 11/25 (44%)
Deaths: 1/25
All Participants
Serious: 17/52 (33%)
Deaths: 2/52

Serious adverse events (35 terms)

ReactionSystemSecukinumabPlaceboAll Participants
Cardiac failureCardiac disorders
FallInjury, poisoning and procedural complications
Pelvic fractureInjury, poisoning and procedural complications
Spinal stenosisMusculoskeletal and connective tissue disorders
Atrial fibrillationCardiac disorders
Atrial tachycardiaCardiac disorders
TachyarrhythmiaCardiac disorders
FaecalomaGastrointestinal disorders
Gastrointestinal painGastrointestinal disorders
MelaenaGastrointestinal disorders
Noninfective sialoadenitisGastrointestinal disorders
General physical health deteriorationGeneral disorders
PyrexiaGeneral disorders
Arthritis bacterialInfections and infestations
ErysipelasInfections and infestations
Urinary tract infectionInfections and infestations
Face injuryInjury, poisoning and procedural complications
Femur fractureInjury, poisoning and procedural complications
Fibula fractureInjury, poisoning and procedural complications
Spinal compression fractureInjury, poisoning and procedural complications
Inflammatory marker increasedInvestigations
Fluid retentionMetabolism and nutrition disorders
Squamous cell carcinoma of lungNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebrovascular accidentNervous system disorders
DizzinessNervous system disorders
Other adverse events (42 terms — click to expand)

ReactionSystemSecukinumabPlaceboAll Participants
HypertensionVascular disorders
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Oedema peripheralGeneral disorders
Urinary tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
Oral candidiasisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
GlaucomaEye disorders
DiarrhoeaGastrointestinal disorders
BursitisMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
HaematomaVascular disorders
CushingoidEndocrine disorders
Vision blurredEye disorders
FatigueGeneral disorders
GastroenteritisInfections and infestations
Respiratory tract infectionInfections and infestations
Skin lacerationInjury, poisoning and procedural complications
Tooth fractureInjury, poisoning and procedural complications
C-reactive protein increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Diabetes mellitusMetabolism and nutrition disorders
OsteoporosisMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
SciaticaNervous system disorders
Tension headacheNervous system disorders
AlopeciaSkin and subcutaneous tissue disorders
Giant cell arteritisVascular disorders
Dental cariesGastrointestinal disorders
Haemorrhoidal haemorrhageGastrointestinal disorders
NauseaGastrointestinal disorders
RhinitisInfections and infestations
Bone contusionInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Rib fractureInjury, poisoning and procedural complications
Thoracic vertebral fractureInjury, poisoning and procedural complications
Blood pressure increasedInvestigations

Most-reported serious reactions: Cardiac failure, Fall, Pelvic fracture, Spinal stenosis, Atrial fibrillation, Atrial tachycardia, Tachyarrhythmia, Faecaloma.

Data from ClinicalTrials.gov NCT03765788 adverse events section.

Sponsor's own description

This study was designed to evaluate the efficacy and safety of secukinumab compared to placebo to maintain disease remission up to 28 weeks including corticosteroid tapering, as well as up to 1 year (52 weeks) in patients with newly diagnosed or relapsing giant cell arteritis (GCA) who were naïve to biological therapy.

Publications & conference data

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

  1. Novel ultrasonographic Halo Score for giant cell arteritis: assessment of diagnostic accuracy and association with ocular ischaemia.
    van der Geest KSM, Borg F, Kayani A, Paap D, et al · · 2020 · cited 85× · PMID 31900304 · DOI 10.1136/annrheumdis-2019-216343
  2. 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
  3. Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases.
    Rafael-Vidal C, Pérez N, Altabás I, Garcia S, et al · · 2020 · cited 50× · PMID 32993066 · DOI 10.3390/ijms21197100
  4. Safety and efficacy of secukinumab in patients with giant cell arteritis (TitAIN): a randomised, double-blind, placebo-controlled, phase 2 trial.
    Venhoff N, Schmidt WA, Bergner R, Rech J, et al · · 2023 · cited 48× · PMID 38251601 · DOI 10.1016/s2665-9913(23)00101-7
  5. Advances in the Treatment of Giant Cell Arteritis.
    Castañeda S, Prieto-Peña D, Vicente-Rabaneda EF, Triguero-Martínez A, et al · · 2022 · cited 27× · PMID 35329914 · DOI 10.3390/jcm11061588
  6. Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial.
    Venhoff N, Schmidt WA, Lamprecht P, Tony HP, et al · · 2021 · cited 27× · PMID 34404463 · DOI 10.1186/s13063-021-05520-1
  7. Reducing the Toxicity of Long-Term Glucocorticoid Treatment in Large Vessel Vasculitis.
    Palmowski A, Buttgereit F. · · 2020 · cited 17× · PMID 33047263 · DOI 10.1007/s11926-020-00961-0
  8. Biologic Therapies for Giant Cell Arteritis.
    Harrington R, Al Nokhatha SA, Conway R. · · 2021 · cited 14× · PMID 33442231 · DOI 10.2147/btt.s229662

Verify or expand the search:

Other trials of Secukinumab 300 mg, s.c.

Trials testing the same drug.

Other recruiting trials for Giant Cell Arteritis

Currently open trials in the same condition.

Other Novartis Pharmaceuticals 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/NCT03765788.

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