A randomized, parallel-group, double-blind, placebo-controlled, multicenter Phase III trial to evaluate efficacy and safety of secukinumab administered subcutaneously versus placebo, in combination with a glucocorticoid taper regimen, in patients with polymyalgia rheumatica (PMR)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

13 Sep 2023 → 17 Feb 2026

Decision date (initial)

2023-09-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To demonstrate that the efficacy of secukinumab 300 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with PMR who have recently relapsed, based on the proportion of participants achieving sustained remission at Week 52

Secondary objectives 13

1. To demonstrate that the efficacy of secukinumab 300 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with PMR who have recently relapsed based on the proportion of participants achieving complete sustained remission at Week 52
2. To demonstrate that the efficacy of secukinumab 150 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with PMR who have recently relapsed based on the proportion of participants achieving sustained remission at Week 52
3. To demonstrate that the efficacy of secukinumab 150 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with PMR who have recently relapsed based on the proportion of participants achieving complete sustained remission at Week 52
4. To demonstrate that the efficacy of secukinumab 300 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with PMR who have recently relapsed based on adjusted annual cumulative GC dose
5. To demonstrate that the efficacy of secukinumab 300 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with PMR who have recently relapsed based on the time to first use of escape treatment or rescue treatment
6. To demonstrate that the efficacy of secukinumab 150 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with PMR who have recently relapsed based on adjusted annual cumulative GC dose
7. To demonstrate that the efficacy of secukinumab 150 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen, in participants with PMR who have recently relapsed based on the time to first use of escape treatment or rescue treatment
8. To demonstrate that the effect on participant's QoL of secukinumab 300 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with PMR who have recently relapsed based on change from baseline (BSL) FACIT-Fatigue score at week 52
9. To demonstrate that the effect on participant's QoL of secukinumab 300 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen, in participants with PMR who have recently relapsed based on change from BSL HAQ-DI score at week 52
10. To demonstrate that the effect on participant's Quality of Life (QoL) of secukinumab 150 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with PMR who have recently relapsed based on change from BSL FACIT-Fatigue score at week 52
11. To demonstrate that the effect on participant's QoL of secukinumab 150 mg s.c. in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen, in participants with PMR who have recently relapsed based on change from BSL HAQ-DI score at week 52
12. To demonstrate the safety and tolerability of secukinumab 300 mg s.c./150 mg s.c. in participants with PMR who have recently relapsed
13. To assess the occurrence of GC-related AEs in participants receiving secukinumab 300 mg s.c./150 mg s.c. versus placebo

Conditions and MedDRA coding

Polymyalgia Rheumatica

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed informed consent must be obtained prior to participation in the study
2. Male or non-pregnant, non-lactating female participants at least 50 years of age
3. Diagnosis of PMR according to the provisional American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria: Participants ≥ 50 years of age with a history of bilateral shoulder pain accompanied by elevated C-reactive protein (CRP) concentration (≥ 10 mg/L) and/or elevated erythrocyte sedimentation rate (ESR) (≥ 30 mm/hr) who scored at least 4 points from the following optional classification criteria: o Morning stiffness > 45 minutes (min) (2 points) o Hip pain or restricted range of motion (1 point) o Absence of rheumatoid factor and/or anti-citrullinated protein antibodies (2 points) *o Absence of other joint involvement (1 point) * These tests can be performed locally at screening if not performed at the time of PMR diagnosis and can be kept at source.
4. Participants must have a history of being treated for at least 8 consecutive weeks with prednisone ≥ 10 mg/day or equivalent dose of another GC at any time prior to screening
5. Participants must have had at least one episode of PMR relapse while attempting to taper prednisone at a dose that is ≥ 5 mg/day (or equivalent dose of another GC) within the past 12 weeks prior to BSL. Diagnosis of a PMR relapse is defined as participant meeting both of the following: o Recurrence of bilateral shoulder girdle and/or bilateral hip girdle pain associated with inflammatory stiffness with or without additional symptoms indicative of PMR relapse (such as constitutional symptoms) within 12 weeks prior to BSL that are in the opinion of the Investigator not due to other diseases that may mimic PMR such as osteoarthritis in shoulders or hips, polyarticular calcium pyrophosphate deposition disease, rotator cuff disease, adhesive capsulitis (frozen shoulder) or fibromyalgia. o Elevated ESR (≥ 30 mm/hr) and/or elevated CRP (> upper limit of normal (ULN)) attributable to PMR at the time of relapse and/or at screening
6. Participants must have been treated as per local treatment recommendations following the latest PMR relapse and must be on prednisone of at least 7.5 mg/day (or equivalent) and not exceeding 25 mg/day at screening and during the screening period
7. A prednisone dose of 15 mg/day or 10 mg/day at BSL is medically appropriate as per Investigator judgment

Exclusion criteria 8

1. Evidence/history of GCA as indicated by typical (cranial) symptoms (e.g., persistent or recurrent localized headache, temporal artery or scalp tenderness, jaw claudication, blurry or loss of vision, symptoms of stroke), extremity claudication, imaging and/or temporal artery biopsy result
2. Concurrent rheumatoid arthritis or other inflammatory arthritis or other connective tissue diseases, such as but not limited to systemic lupus erythematosus, systemic sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing spondylitis
3. Concurrent diagnosis or history of neuropathic muscular diseases or fibromyalgia
4. Inadequately treated hypothyroidism (e.g., persistence of symptoms, lack of normalization of serum TSH despite regular hormonal replacement treatment)
5. Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor
6. Participants treated with tocilizumab or other IL-6/IL6-receptor inhibitors within 12 weeks or within 5 half-lives (whichever is longer) prior to BSL; participant who did not respond to or experienced a relapse during treatment are excluded from enrollment into the study
7. History of hypersensitivity or contraindication to any of the study treatments or its excipients or to drugs of similar chemical classes.
8. Major ischemic event (e.g., myocardial infarction, stroke, etc.) or transient ischemic attack (TIA) within 12 weeks of screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants achieving sustained remission at Week 52

Secondary endpoints 13

1. Proportion of participants achieving complete sustained remission at Week 52
2. Proportion of participants achieving sustained remission at Week 52
3. Proportion of participants achieving complete sustained remission at Week 52
4. Adjusted annual cumulative GC dose through Week 52 adjusted by duration of study follow-up
5. Time to first use of escape treatment or rescue treatment as measured in days through Week 52
6. Adjusted annual cumulative GC dose through Week 52 adjusted by duration of study follow-up
7. Time to first use of escape treatment or rescue treatment as measured in days through Week 52
8. Change from BSL FACIT-Fatigue score at Week 52
9. Change from BSL HAQ-DI score at Week 52
10. Change from BSL FACIT-Fatigue score at Week 52
11. Change from BSL HAQ-DI score at Week 52
12. Safety and tolerability demonstrated by assessing: - All adverse events (AEs) and all serious adverse events (SAEs) (incidence, severity, and relationship to study drug) - Clinically significant changes in clinical laboratory measures and vital signs
13. AEs that are related to GC use by investigator judgement

Investigational products

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

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 23

Locations

15 EU/EEA countries · 75 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 218 files

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

Application history

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