What clinical trials have been conducted for Secukinumab?

Introduction to Secukinumab
Secukinumab is a fully human monoclonal IgG1κ antibody that selectively neutralizes interleukin (IL)-17A, a pro-inflammatory cytokine critically involved in several immune-mediated inflammatory diseases. In recent years, secukinumab has emerged as a cornerstone in the management of various conditions such as plaque psoriasis, psoriatic arthritis (PsA), ankylosing spondylitis (AS), hidradenitis suppurativa (HS), and even conditions with more exploratory indications like lupus nephritis. Its mechanism of action – the inhibition of IL-17A – interrupts inflammatory cascades that drive disease activity, leading to substantial and sustained clinical improvements in multiple domains of disease activity as observed in both pivotal clinical trials and real-world studies.

Mechanism of Action
Secukinumab directly binds to IL-17A, blocking the cytokine’s interaction with its receptor and thereby inhibiting a downstream cascade of inflammatory mediators. This targeted inhibition reduces inflammation, keratinocyte activation, and the recruitment of immune cells into affected tissues. The precise modulation of the immune response contributes significantly to its therapeutic efficacy across a spectrum of inflammatory diseases. This mechanism also underpins many of its observed clinical benefits, such as the rapid clearance of psoriatic lesions and improvement in joint symptoms in PsA patients.

Therapeutic Indications
Secukinumab is approved for a multitude of indications. It is well established in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis, with robust data supporting its use from multiple phase III clinical trials. Additionally, its efficacy has been demonstrated in patients with ankylosing spondylitis, and emerging evidence supports its potential use in hidradenitis suppurativa. There are also exploratory studies evaluating its use in other autoimmune conditions such as lupus nephritis, where it is being compared to placebo in combination with standard-of-care therapies. Its versatile therapeutic profile has made secukinumab an attractive candidate not only for established indications but also for further investigations into its role in additional immune-mediated disorders.

Overview of Clinical Trials
Clinical trials have played a critical role in establishing the efficacy and safety profile of secukinumab. These trials have spanned multiple phases, from early proof-of-concept studies to expansive phase III trials that have led to regulatory approval.

Phases of Clinical Trials
The clinical trial journey for secukinumab has followed the standard phases required for pharmaceutical drug development.
- Phase I Trials assessed the pharmacokinetics, safety, and tolerability of secukinumab in humans, setting the stage for dose selection and safety monitoring.
- Phase II Trials focused on determining the effective therapeutic dose and further evaluated its safety profile as well as initial indications of efficacy in smaller patient populations.
- Phase III Trials were pivotal; large-scale randomized, double-blind, placebo-controlled studies demonstrated robust efficacy and a favorable safety profile across diverse patient populations with conditions such as psoriasis, PsA, AS, and HS. These trials have provided in-depth data on primary endpoints such as the ACR20 response in PsA, PASI75 (and higher) responses in psoriasis, and ASAS responses in ankylosing spondylitis.
- Phase IV Trials and Extension Studies have continued to provide valuable real-world data and long-term safety information. For example, extension studies have reported sustained efficacy and safety outcomes in patients receiving secukinumab beyond initial clinical trial periods, spanning up to 5–6 years in some instances.

Importance in Drug Development
Secukinumab’s journey through clinical trials underscores the importance of these studies in de-risking the therapeutic candidate while providing statistically robust evidence of efficacy and long-term safety. Each phase of the trials has contributed insights into dosing strategies, treatment durability, quality-of-life improvements, and the management of potential side effects. Moreover, successful clinical trials have paved the way for secukinumab’s regulatory approvals worldwide and have established it as an effective biologic with a definitive role in modern therapeutic regimens for immune-mediated inflammatory diseases.

Detailed Analysis of Secukinumab Clinical Trials

A comprehensive review of the clinical trials conducted with secukinumab reveals an extensive portfolio spanning multiple indications and study designs. Below, we provide a detailed analysis of completed and ongoing trials, along with a discussion of their outcomes and implications.

Completed Trials

1. Plaque Psoriasis Trials
- A Phase III clinical trial compared the efficacy and safety of SYS6012 injection [an investigational product] with secukinumab injection (Cosentyx®) in the treatment of moderate-to-severe plaque psoriasis. This trial employed a multicenter, randomized, double-blind, parallel, positive-controlled design. The primary objectives were to evaluate clinical equivalence in terms of skin clearance and safety endpoints such as adverse events.
- Additional phase III studies, such as FUTURE 1 and FUTURE 2, demonstrated long-term efficacy with sustained PASI responses (PASI 75, PASI 90, and even PASI 100) over time, reflecting the rapid onset of action and sustained skin clearance observed with secukinumab. In these trials, improvements in the Dermatology Life Quality Index (DLQI) and patient-reported outcomes further underscored the clinical benefits.

2. Psoriatic Arthritis (PsA) Trials
- Several pivotal studies assessed secukinumab in the treatment of psoriatic arthritis. For example, the FUTURE 1 trial enrolled patients with active PsA, evaluating joint symptoms via ACR response criteria (including ACR20/50/70) along with improvements in radiographic progression scores. Results from these trials showed sustained reductions in joint inflammation and maintained improvements in physical function for up to 3–5 years.
- A Phase III extension study further monitored long-term safety and sustained clinical responses, with improvements preserved even in patients with prior anti-TNF exposure. These studies have largely confirmed that secukinumab is effective irrespective of prior biologic usage.

3. Ankylosing Spondylitis (AS) Trials
- Secukinumab’s use in ankylosing spondylitis was evaluated in multiple trials, including China-centric studies such as MEASURE 5 and MEASURE 2. In these studies, patients with active AS were enrolled and randomized to receive secukinumab 150 mg with a specific dosing schedule after an initial loading phase. Primary endpoints such as ASAS20 and ASAS40 were met, supporting significant improvements in axial symptoms and spinal mobility. Moreover, MRI studies within these trials showed a reduction in spinal inflammation as early as week 6, with sustained benefits accessed over 3 years in MEASURE 2.
- Additional data from the MEASURE trials have highlighted the benefit of secukinumab even in patients with previous exposure to TNF inhibitors and showcased a low rate of radiographic progression, further solidifying its role as an effective treatment option for AS.

4. Hidradenitis Suppurativa (HS) Trials
- Several clinical trials have been conducted in patients with moderate-to-severe hidradenitis suppurativa. One important trial is a randomized study comparing secukinumab with tofacitinib in Chinese patients, which aimed to delineate the efficacy and safety profiles of these two agents in HS.
- Another study, referenced as ILLUMINATE-HS, was a prospective trial assessing short-term treatment satisfaction and quality-of-life improvements in HS patients initiated on secukinumab in routine clinical practice in the United Arab Emirates.
- A real-world, observational study was also carried out in Russia (ANIMA-R study), designed to collect data on treatment patterns and persistence in adult HS patients.
- These trials have demonstrated that secukinumab offers rapid symptomatic improvement and a reduction in the disease burden associated with HS, with safety outcomes comparable to those observed in psoriasis and PsA groups.

5. Pediatric Populations
- A prospective observational study assessed the effectiveness of secukinumab in pediatric patients with active juvenile enthesitis-related arthritis or psoriatic arthritis. This study provided data on dosing, pharmacokinetics, and overall tolerability in a younger population, highlighting that secukinumab can be safely and effectively used beyond adult patients.
- An open-label, multicenter study evaluated the pharmacokinetics, safety, and tolerability of intravenous secukinumab in pediatric patients with juvenile psoriatic arthritis (JPsA) over a prolonged period (up to 6 years). The study reinforced the long-term safety profile, with minimal adverse events and sustained benefit in disease activity scores.

6. Comparative and Head-to-Head Trials
- An interesting trial compared ixekizumab versus secukinumab (termed as secukizumab in the reference) in patients aged over 70 years with moderate-to-severe plaque psoriasis, offering insights about the performance of different IL-17 inhibitors in an elderly population. Although ixekizumab was included as a comparator in this head-to-head study, the results provided valuable context regarding the efficacy and tolerability of secukinumab in populations with potentially altered pharmacodynamics due to age.
- Another trial evaluated the efficacy of injection sekucinumab in erythrodermic psoriasis, further broadening the spectrum of psoriasis subtypes being addressed and validating secukinumab’s utility in more severe and complex presentations of the disease.
- In addition, a trial comparing CT-P55 (a biosimilar candidate) with Cosentyx (brand names for secukinumab) in moderate-to-severe psoriasis provided comparative data in a controlled setting, supporting safety and efficacy equivalence between the investigational biosimilar and the established product.
- A phase III study comparing CMAB015 with Cosentyx further advanced our understanding by evaluating immunogenicity, safety, and efficacy outcomes – thus providing comparative data that are essential when establishing secukinumab’s clinical risk profile relative to other biologics.

7. Lupus Nephritis Exploration
- Two similar clinical trials have been conducted evaluating the safety, efficacy, and tolerability of secukinumab versus placebo in patients with active lupus nephritis. Although these trials are relatively unique in their patient population compared with the more common dermatological and rheumatologic indications, their design has contributed additional insights on potential expanded indications. Both trials employed a rigorous two-year, phase III randomized, double-blind, placebo-controlled design to assess secukinumab in combination with standard-of-care therapies, thereby exploring its therapeutic potential in renal autoimmune inflammation.

8. Other Completed Studies
- Additional retrospective and observational studies have also played a critical role in assessing secukinumab’s drug survival, real-world effectiveness, and patient satisfaction. For instance, real-world studies using claims databases have provided insights into treatment persistence in patients with psoriatic arthritis in Japan. Similarly, a multicenter prospective observational study examined patients’ perspectives on the evolution of the HS burden after secukinumab initiation, contributing qualitative data on treatment satisfaction.
- These studies are crucial complements to randomized controlled trials as they provide context on long-term outcomes in routine clinical practice settings, thereby reinforcing the overall favorable safety and efficacy profile of secukinumab.

Ongoing Trials

1. Extension and Roll-over Studies
- The Secukinumab Open Label Roll-over Extension Protocol is a study designed for patients who have completed previous Novartis-sponsored secukinumab studies and continue to be judged as benefiting from treatment. This roll-over extension allows investigators to collect long-term safety and efficacy data beyond the controlled periods of initial phase III trials. Such extensions are instrumental in understanding long-term drug survival, adverse event incidence, and continued therapeutic benefit.

2. Exploratory and Drug Monitoring Studies
- An ongoing trial is focusing on the therapeutic drug monitoring (TDM) of secukinumab in psoriasis patients. This study evaluates early serum trough concentrations, anti-drug antibody formation, and the development of a concentration–response curve. Such studies are imperative for refining dosing strategies and understanding the pharmacokinetic–pharmacodynamic relationships to further optimize therapy.
- Similarly, an exploratory trial evaluating Cosentyx (secukinumab) in patients with moderate-to-severe hidradenitis suppurativa is being conducted at a single site. This study is investigator-initiated and aims to elucidate efficacy signals for HS, potentially leading to expanded indications in this challenging patient population.

3. Clinical Outcome Trials in Specific Populations
- Ongoing clinical trials focusing on the impact of secukinumab on clinical and patient-reported outcomes in patients with psoriasis in the US (for example, the Bionaive Secukinumab Users study) are designed to assess real-world effectiveness. These trials include detailed analyses of improvements in body surface area, Investigator’s Global Assessment scores, and PASI scores over 6 to 12 months, with stratification based on biologic-naive versus biologic-experienced patients.
- This kind of study is crucial in discerning how earlier-line use of secukinumab compares with subsequent lines of therapy in routine practice and may also influence future treatment guidelines and reimbursement policies.

Trial Outcomes and Results

The accumulated data from both completed and ongoing clinical trials of secukinumab reveal several key aspects of its therapeutic profile:

1. Efficacy Metrics
- Psoriasis: Major outcomes include high PASI75, PASI90, and even PASI100 responses in multiple phase III studies. These improvements not only reflect skin clearance but also correlate with significant enhancements in quality-of-life measures such as DLQI. The CLEAR and FUTURE trials have demonstrated that secukinumab is one of the most effective biologics for psoriasis, with rapid onset and sustained responses over years of therapy.
- Psoriatic Arthritis: Significant improvements in ACR20, ACR50, and ACR70 response rates have been recorded across trials such as FUTURE 1 and FUTURE 2. Additionally, radiographic analysis has indicated slowed structural damage progression, and the improvements in joint function have been sustained even when patients were previously exposed to TNF inhibitors.
- Ankylosing Spondylitis: Trials such as MEASURE 2 and MEASURE 5 have shown that secukinumab significantly improves ASAS20 and ASAS40 response rates while also reducing spinal inflammation as confirmed by MRI findings. These benefits have been maintained in long-term follow-up, supporting its role as a durable therapy for axial disease.
- Hidradenitis Suppurativa: The trials targeting HS—including the randomized study comparing secukinumab with tofacitinib and observational studies in different regions—demonstrate that secukinumab yields rapid symptomatic improvements, enhances treatment satisfaction, and reduces overall disease burden. These outcomes are particularly important given the recalcitrant and painful nature of HS.
- Lupus Nephritis: Although data are more preliminary, the two trials assessing secukinumab in lupus nephritis have shown promising signs in terms of safety and tolerability, warranting further exploration into renal autoimmune conditions.

2. Safety and Tolerability
- Across multiple studies, secukinumab has maintained a favorable safety profile. The incidence of serious adverse events remains low, and common adverse events are usually limited to infections (most commonly nasopharyngitis), mild-to-moderate Candida infections, and occasional gastrointestinal disturbances.
- Long-term extension studies and open-label trials have not revealed any new safety signals even after several years of treatment, further supporting its use in chronic conditions.
- The safety outcomes observed in pediatric populations and in older patients (as in the head-to-head trials with ixekizumab) also extend the promising tolerability profile of secukinumab across varied age groups and patient characteristics.

3. Patient-Reported Outcomes
- In addition to objective clinical measures, numerous trials have assessed patient-reported outcomes, including quality-of-life indices, treatment satisfaction questionnaires, and other patient-centric endpoints. These studies have consistently demonstrated that secukinumab leads to significant improvements in overall quality of life, reduced symptom burden, and enhanced satisfaction levels compared to baseline measures—further reinforcing its clinical value.
- Real-world studies, such as those conducted using claims data and registry analyses, have echoed these findings, highlighting high rates of drug survival and patient adherence over prolonged treatment periods.

4. Pharmacokinetics and Drug Monitoring
- The ongoing and completed studies investigating the pharmacokinetics of secukinumab have elucidated important aspects such as serum trough concentrations and the occurrence of anti-drug antibodies. These studies have helped establish a robust concentration–response relationship, critical for optimizing dosing regimens and ensuring sustained therapeutic efficacy while minimizing the risk of immunogenicity.

Implications and Future Directions

The extensive clinical trial portfolio of secukinumab has implications for both current clinical practice and future research in the field of biologic therapies.

Clinical Implications
1. Enhanced Treatment Efficacy Across Multiple Indications
- Secukinumab has proven to be a highly effective treatment option for conditions including moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. The rapid onset of action and sustained responses translate into meaningful improvements in both clinical outcomes and patient quality of life.
- Its performance in difficult-to-treat subpopulations, such as biologic-experienced or elderly patients, emphasizes its flexibility as a therapeutic option. Moreover, the positive outcomes in conditions like hidradenitis suppurativa and exploratory trials in lupus nephritis broaden its potential clinical applications significantly.

2. Safety Profile and Long-Term Tolerability
- A favorable safety profile, consistent across multiple trials and extension studies, provides confidence in its long-term utilization. The low rate of serious adverse events and the preservation of drug effectiveness even in chronic settings are particularly valuable in diseases that require lifelong management.
- These safety outcomes also support its use in pediatric populations and in patients with significant comorbidities, thereby expanding the demographic reach of secukinumab.

3. Patient-Centric Benefits and Real-World Validation
- Improved patient-reported outcomes and treatment satisfaction scores have solidified secukinumab’s role in real-world practice. Observational studies and registry data have confirmed that the clinical benefits observed under controlled trial conditions translate effectively into everyday medical practice, which is essential for chronic diseases like psoriasis and PsA.
- The increasing proportion of biologic-naïve patients initiating secukinumab in recent years is indicative of growing clinician confidence and its potential consideration as a first-line biologic in certain inflammatory dermatoses.

Future Research and Development
1. Expanding Indications and Optimizing Treatment Strategies
- Future research may focus on expanding the therapeutic indications for secukinumab beyond its current approvals. Ongoing trials in conditions such as lupus nephritis and exploratory studies in rare inflammatory diseases will further elucidate its full clinical potential.
- Additionally, the design of head-to-head and comparative studies with other biologics—especially with new generation IL-17 inhibitors—will refine its positioning in treatment algorithms and may lead to personalized treatment strategies based on patient subgroups.

2. Refinement of Pharmacokinetic and Pharmacodynamic Models
- The continuing research into therapeutic drug monitoring and pharmacokinetic profiling is expected to optimize dosing strategies. Understanding the concentration–response relationship and the impact of anti-drug antibodies will be crucial in determining individualized dosing regimens that achieve optimal therapeutic outcomes while mitigating adverse effects.
- The development of biomarker-driven approaches and further characterization of the immunogenic profile might lead to even safer and more effective long-term administration protocols.

3. Long-Term Real-World Evidence Generation
- While clinical trials provide the gold standard evidence for efficacy and safety, long-term real-world studies will continue to be of paramount importance in understanding drug survival, patient adherence, and quality-of-life improvements over extended periods.
- Future registries and observational studies should aim to capture data from increasingly diverse patient populations, especially considering racial, ethnic, and socioeconomic variables that can influence therapeutic outcomes.

4. Combination Regimens and Multi-Targeted Approaches
- Investigations into combination regimens, such as pairing secukinumab with TNF inhibitors or other biologics, may offer enhanced therapeutic benefits in patients with refractory or multi-faceted disease presentations.
- Such combination studies will need to carefully assess the safety profile and potential pharmacodynamic interactions while striving to achieve synergistic improvements in clinical outcomes.

Conclusion

Secukinumab has undergone an extensive array of clinical trials spanning multiple phases, indications, and patient demographics. In psoriasis, clinical trials have delivered robust evidence for significant PASI improvements, supporting both rapid onset of action and maintained efficacy over years of treatment. In psoriatic arthritis, secukinumab has demonstrated profound benefits on joint symptoms with favorable radiographic outcomes and functional improvements. The series of trials addressing ankylosing spondylitis confirm its efficacy in reducing spinal inflammation as well as in improving axial symptoms as measured by ASAS response criteria. Moreover, trials in hidradenitis suppurativa have provided encouraging signals for a challenging disease, prompting further research. Additionally, exploratory studies in lupus nephritis and pediatric trials in juvenile psoriatic arthritis add further dimensions to its clinical application.

Ongoing clinical trials—including open-label roll-over extensions, therapeutic drug monitoring studies, and registry-based real-world analyses—continue to expand our understanding of secukinumab’s pharmacokinetics, long-term tolerability, and optimal use in various populations. The comparative studies with other IL-17 inhibitors and biosimilars further position secukinumab as a benchmark in its class, supporting its continued evolution in indications and dosing strategies.

In conclusion, the clinical trials conducted for secukinumab, as referenced from numerous structured synapse source documents, collectively demonstrate its robust efficacy, favorable safety profile, and versatility across a spectrum of immune-mediated inflammatory diseases. Secukinumab has not only reshaped the treatment paradigm for psoriasis and psoriatic arthritis but also holds immense promise for conditions such as ankylosing spondylitis and hidradenitis suppurativa. Ongoing research and long-term real-world evidence continue to highlight its benefits and will guide future developments in biologic therapies. The detailed clinical trial data provide a powerful testament to secukinumab’s role in modern medicine and underscore the importance of continued research into its optimal use and potential new indications.