Clinical trial NCT06470048: A Clinical Study to Evaluate Ianalumab in Participants With Diffuse Cutaneous Systemic Sclerosis
Official title: A Randomized, Double-blind, Parallel Group, Placebo-controlled Multicenter Study to Evaluate Efficacy, Safety and Tolerability of Ianalumab in Participants With Diffuse Cutaneous Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Cutaneous Systemic Sclerosis
Keywords: Diffuse Cutaneous Systemic Sclerosis (dcSSc)
Diffuse Scleroderma
Diffuse Systemic Sclerosis
Scleroderma, Diffuse
Scleroderma, Progressive
Sclerosis, Progressive Systemic
Sudden Onset Scleroderma
B cell depletion
Revised Composite Response Index in Systemic Sclerosis 25 (rCRISS25)
modified Rodnan skin score
forced vital capacity
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-06-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate efficacy, safety and tolerability of s.c. ianalumab administered in participants with diffuse cutaneous systemic sclerosis relative to placebo

Detailed description: The study consists of the following periods:

* Screening Period, with a duration of up to 6 weeks;
* Treatment Period 1, with a duration of 52 weeks;
* Treatment Period 2 (Open-label treatment), with a duration of 52 weeks;
* Post-treatment Follow-up Period, with a duration of at least 20 weeks post last dose and up to 2 years.

Eligibility criteria: Key Inclusion Criteria:

* Male and female participants \>= 18 and =\< 70 years (at the time of the screening visit).
* Diagnosis of systemic sclerosis, as defined by the 2013 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria for SSc (van den Hoogen et al 2013) and meet the dcSSc subset classification according to LeRoy (LeRoy 1988)
* Disease duration of =\< 60 months (defined as time from the first non-Raynaud phenomenon manifestation, e.g., puffy hands, scleroderma, digital ulcers, arthralgia, dyspnea)
* mRSS units of \>= 15 and =\< 45 at the time of the screening visit
* Active disease that meets at least one of the following criteria at screening:

  * Disease duration of =\< 18 months defined as time from the first non-Raynaud phenomenon manifestation
  * Increase in mRSS of \>= 3 units compared with the most recent assessment performed within the previous 6 months
  * Involvement of one new body area and an increase in mRSS of \>= 2 units compared with the most recent assessment performed within the previous 6 months
  * Involvement of two new body areas within the previous 6 months
  * Elevated acute phase reactants (ESR) \>= 30 mm/hr or high-sensitivity C-reactive protein (hsCRP) \>= 6 mg/dL)
  * Presence of interstitial lung disease (ILD) and ATA autoantibody positivity
  * Modified EUSTAR disease activity index (mDAI) \> 2.5
* Participant must be positive for at least one of the following autoantibodies:

  * anti-topoisomerase I (ATA) (also known as anti-SCL-70)
  * anti-RNA polymerase III (anti-RNAP3)
  * anti-nuclear antibody (ANA) (≥ 1:80) Participants who are positive only for ANA (while being negative for both ATA /anti-RNAP3) will be limited to 30% of the overall randomized study population.

Key Exclusion Criteria:

* Rheumatic disease other than dcSSc, including limited cutaneous disease (lcSSc) or sine scleroderma at the screening visit. Secondary Sjogren's disease and scleroderma myopathy are not exclusionary.
* Positive anti-centromere antibody (ACA+) without positive ATA or anti-RNAP3 autoantibody result at the screening visit
* Previous improvement (decrease) in mRSS \> 10 units
* Pulmonary disease with FVC ≤ 50% of predicted or diffusing capacity of the lung for carbon monoxide (DLCO, corrected for hemoglobin) ≤ 40% of predicted at the screening visit
* WHO Functional Class 3 or higher assessment for pulmonary arterial hypertension (PAH, as defined on right heart catheterization), receiving IV therapy for PAH or evidence of other moderately severe pulmonary disease
* Participants treated with cyclophosphamide within 12 weeks prior to Baseline.
* Prior use of a B-cell depleting therapy other than ianalumab (e.g., rituximab, other anti-CD20 mAb, anti-CD22 mAb, or anti-CD52 mAb) administered within 36 weeks prior to randomization, or as long as B cell count is less than the lower limit of normal or baseline value prior to receipt of B cell-depleting therapy (whichever is lower)
* Treatment with biologic agents, such as intravenous immunoglobulin or monoclonal antibodies, including marketed drugs, within 12 weeks or 5 half-lives (whichever is longer) prior to baseline visit, unless explicitly allowed in inclusion criteria
* Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the baseline visit
* Use of anti-fibrotic agents including colchicine, D-penicillamine, pirfenidone, or tyrosine kinase inhibitors (e.g., nintedanib, nilotinib, imatinib, dasatinib) in the 4 weeks prior to baseline visit.
* Previous treatment with chlorambucil, bone marrow transplantation or total lymphoid irradiation.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: 3/5 rCRISS25 response
timeFrame: Week 52
Secondary outcomes:
measure: Change from baseline in FVC% predicted at Week 52
timeFrame: Week 52
measure: Change from baseline in mRSS at Week 52
timeFrame: Week 52
measure: Change from baseline in HAQ-DI at Week 52
timeFrame: Week 52
measure: Ianalumab concentrations in serum during treatment and Follow-up Period
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, Week 64, Week 76, Week 88, Week 104, Week 108, Week 112, Week 116, Week 120, Week 124 and Week 208
measure: Incidence and titer of anti-drug (ianalumab) antibodies (ADAs) in serum over time
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, Week 64, Week 76, Week 88, Week 104, Week 124, Week 208
measure: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 208
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: Clinical Res Of W Florida
state: Florida
city: Sarasota
country: United States
facility: Sarasota Arthritis Res Ctr
state: Florida
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Allen
country: United States
facility: Arthritis and Rheumatology Ins
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Nanning
country: China
facility: Novartis Investigative Site
state: Guangxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Beijing
country: China
facility: Novartis Investigative Site
city: Zhejiang
country: China
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Kochi
country: India
facility: Novartis Investigative Site
state: Kerala
city: Mumbai
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Jaipur
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Vila Nova De Gaia
country: Portugal
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Changhua
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Khon Kaen
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
state: VNM
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: