Ianalumab for Autoimmune Diseases

Recruiting at 31 trial locations

Overseen By Shirley Pang

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Infections, Live vaccines, Pregnancy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to demonstrate the comparability of ianalumab exposure following the sub-cutaneous (s.c.) administration of one injection of 300 mg/2 mL auto-injector (AI) versus two injections of 150 mg/1 mL pre-filled syringe (PFS), and to evaluate the safety and tolerability of ianalumab following the s.c. administration of both devices in participants with rheumatoid arthritis (RA), Sjögren's disease (SjD), or systemic lupus erythematosus (SLE). A second optional cohort may be included with the objective of demonstrating the comparability of pharmacokinetics of ianalumab between 1 x 2 mL Pre-filled Syringe (PFS) and 2 x 1 mL PFS.

Do I need to stop my current medications to join the trial?

The trial requires that participants be on stable doses of their current medications for 4 weeks before starting the study treatment. This means you should not change your current medications before joining the trial.

Is ianalumab (VAY736) safe for humans?

Ianalumab (VAY736) has been tested for safety in patients with primary Sjögren's syndrome, an autoimmune disease, in clinical trials. These studies were designed to evaluate both the safety and effectiveness of the treatment, indicating that safety data has been collected during these trials. ^{1 2 3 4 5}

What makes the drug Ianalumab unique for treating autoimmune diseases?

Ianalumab is unique because it targets specific immune system components, potentially offering a more precise approach compared to traditional treatments like intravenous immunoglobulin (IVIG), which broadly modulates the immune system. This targeted mechanism may lead to fewer side effects and improved efficacy for certain autoimmune conditions. ^{6 7 8 9 10}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for adults aged 18-70 with autoimmune diseases like RA, Sjögren's disease, or lupus. Participants must weigh between 35-150 kg with a BMI of 18-35 and have active disease that could benefit from B-cell depletion therapy. They should be on stable doses of standard treatments for at least four weeks before the study starts.

Inclusion Criteria

My condition (RA, Sjögren's, or lupus) might improve with B-cell therapy.

Key

I have signed the consent form for this trial.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment Period 1

Participants receive ianalumab 300 mg s.c. in one of two sequences, with a treatment switch at Week 12

12 weeks

Monthly visits

Treatment Period 2

Participants continue with the alternate treatment sequence of ianalumab 300 mg s.c.

12 weeks

Monthly visits

Extended Treatment Period

Participants have the option to continue receiving ianalumab 300 mg s.c. monthly

48 weeks

Monthly visits

Mandatory Post-Treatment Safety Follow-up

Participants are monitored for safety after the last study treatment

16 weeks

Conditional Post-Treatment Safety Follow-up

Participants are monitored until B-cell recovery or up to 2 years

up to 88 weeks

Treatment Details

Interventions

• Ianalumab (Monoclonal Antibodies)

Trial Overview The study tests if ianalumab given by a new auto-injector (300 mg/2 mL) is comparable to the current method using pre-filled syringes (two injections of 150 mg/1 mL). It also assesses safety and tolerability in patients with rheumatoid arthritis, Sjögren's disease, or systemic lupus erythematosus.

Participant Groups

Group I: Cohort 2: Sequence 2 + Upper Arm Experimental Treatment 2 Interventions

Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Upper Arm 2. x 1 mL) PFS in TP2 in Upper Arm (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm

Group II: Cohort 2: Sequence 2 + Thigh Experimental Treatment 2 Interventions

Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Thigh 2. x 1 mL) PFS in TP2 in Thigh (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm

Group III: Cohort 2: Sequence 2 + Abdomen Experimental Treatment 2 Interventions

Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Abdomen (1 X 2 mL) PFS in TP2 in Abdomen (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm

Group IV: Cohort 2: Sequence 1 + Upper Arm Experimental Treatment 2 Interventions

Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Upper Arm (1 X 2 mL) PFS in TP2 in Upper Arm (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm

Group V: Cohort 2: Sequence 1 + Thigh Experimental Treatment 2 Interventions

Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) PFS in TP2 in Thigh (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm

Group VI: Cohort 2: Sequence 1 + Abdomen Experimental Treatment 2 Interventions

Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm

Group VII: Cohort 1: Sequence 2 + Thigh Experimental Treatment 2 Interventions

Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) AI in TP2 in Thigh (1 x 2 mL) AI in ETP in Thigh/ Abdomen

Group VIII: Cohort 1: Sequence 2 + Abdomen Experimental Treatment 2 Interventions

Patients randomized to receive injection 1. X 2 mL) AI in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen

Group IX: Cohort 1: Sequence 1 + Thigh Experimental Treatment 2 Interventions

Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) AI in TP2 in Thigh (1 x 2 mL) AI in ETP in Thigh/ Abdomen

Group X: Cohort 1: Sequence 1 + Abdomen Experimental Treatment 2 Interventions

Patients randomized to receive injection 1. X 2 mL) AI in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

Ianalumab, a new biologic treatment for primary Sjögren's syndrome, demonstrated a dose-related decrease in disease activity after 24 weeks, with the most significant improvement seen in the 300 mg dose group.

The treatment was generally well tolerated, with no increase in infections reported, indicating a favorable safety profile for patients with moderate to severe disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Bowman, SJ., Fox, R., Dörner, T., et al.[2022]

Ianalumab (VAY736) demonstrated significant efficacy in reducing disease activity in patients with active primary Sjögren's syndrome, as shown by improvements in multiple clinical outcomes compared to placebo, including the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).

The treatment resulted in rapid and sustained B cell depletion after a single infusion, with mild to moderate infusion reactions being the main side effects, indicating a favorable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of primary Sjögren's syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. Dörner, T., Posch, MG., Li, Y., et al.[2020]

In a 5-year study involving 2,228 patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, subcutaneous golimumab (GOL) demonstrated a safety profile consistent with previous findings, showing lower rates of serious infections compared to placebo.

However, higher doses of GOL (100 mg) were associated with increased incidences of tuberculosis, opportunistic infections, lymphoma, and demyelination compared to the lower dose (50 mg), suggesting careful monitoring is needed for patients on higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis. Kay, J., Fleischmann, R., Keystone, E., et al.[2018]

In a study of 208 patients with active ankylosing spondylitis, intravenous golimumab (GOL) demonstrated significant efficacy, with 69.5% of patients achieving an ASAS20 response at 52 weeks, compared to 65.0% in the placebo crossover group.

The safety profile of GOL was consistent with previous findings, with 55.4% of patients experiencing at least one adverse event and only 3.4% reporting serious adverse events, indicating that GOL is a safe treatment option for active ankylosing spondylitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intravenous Golimumab in Adults with Ankylosing Spondylitis: Results through 1 Year of the GO-ALIVE Study. Reveille, JD., Deodhar, A., Caldron, PH., et al.[2020]

In a 5-year study of 70 patients with active rheumatoid arthritis, adalimumab (ADA) significantly improved disease activity, with a mean DAS28 score reduction from 6.5 to 3.6, indicating better control of symptoms.

The treatment also showed a favorable safety profile, with 60% of patients responding positively and 35.7% achieving remission, while only 14.28% experienced treatment failure requiring a switch to another biological agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab therapy in patients with active rheumatoid arthritis. Ancuţa, C., Ancuţa, E., Miu, S., et al.[2015]

Intravenous immunoglobulin (IVIG) is a widely used and relatively safe treatment for various conditions, including antibody deficiencies, autoimmune diseases, and certain infections, with established efficacy in clinical trials for disorders like idiopathic thrombocytopenic purpura and Guillain-Barré syndrome.

Despite its effectiveness, there is a lack of standardized therapeutic guidelines for IVIG use, including dosage and timing, highlighting the need for more multicentric controlled clinical trials to better document its benefits and cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intravenously applied immunoglobulin in systemic, autoimmune and vasculitis diseases in children]. Zeman, K., Cywińska-Bernas, A.[2011]

The study evaluated two IgG subfractions from intravenous immunoglobulins (IVIg) and found that the anti-DNP fraction significantly protected against inflammation in models of autoimmune diseases, such as collagen-induced arthritis and experimental autoimmune encephalomyelitis in rats.

The anti-DNP fraction also reduced the incidence of spontaneous diabetes in nonobese diabetic mice at lower concentrations than standard IVIg, suggesting its potential for more effective treatment with fewer side effects by modulating proinflammatory cytokines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyreactive autoantibodies purified from human intravenous immunoglobulins prevent the development of experimental autoimmune diseases. Bruley-Rosset, M., Mouthon, L., Chanseaud, Y., et al.[2023]

In a study involving 10 patients with severe, treatment-resistant rheumatoid arthritis, high-dose intravenous immunoglobulin (IVIg) led to significant improvements in disease activity for all 9 patients who completed the treatment over 6 months.

The therapeutic effects of IVIg may be linked to its impact on specific immune cell ratios, particularly the CD4+CD45RA+ subset, although the benefits were temporary, with all patients experiencing a relapse after treatment cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose immunoglobulin therapy as an immunomodulatory treatment of rheumatoid arthritis. Tumiati, B., Casoli, P., Veneziani, M., et al.[2019]

Immune checkpoints (ICPs) play a crucial role in maintaining immune tolerance, and their mechanisms have been validated as therapeutic targets for treating autoimmune diseases like multiple sclerosis and type-1 diabetes.

Recent clinical findings suggest that targeting ICPs can restore immune tolerance, with various therapeutic agents (such as antibodies and fusion proteins) showing promise, although safety considerations are essential for their development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoints, a Novel Class of Therapeutic Targets for Autoimmune Diseases. Zhai, Y., Moosavi, R., Chen, M.[2022]

In a study of 10 patients with severe pyoderma gangrenosum (PG), 7 patients experienced clearance of PG lesions after treatment with intravenous immunoglobulin (IVIG), suggesting its potential efficacy as an adjunct therapy.

While IVIG showed promise in treating PG, some patients reported side effects, including nausea and one case of aseptic meningitis, indicating that while generally acceptable, monitoring for adverse reactions is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of pyoderma gangrenosum with intravenous immunoglobulin. Cummins, DL., Anhalt, GJ., Monahan, T., et al.[2008]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of primary Sjögren's syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. [2020]

3. Canada pubmed.ncbi.nlm.nih.gov

Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis. [2018]

4. Canada pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intravenous Golimumab in Adults with Ankylosing Spondylitis: Results through 1 Year of the GO-ALIVE Study. [2020]

5. Romania pubmed.ncbi.nlm.nih.gov

Adalimumab therapy in patients with active rheumatoid arthritis. [2015]

6. Poland pubmed.ncbi.nlm.nih.gov

[Intravenously applied immunoglobulin in systemic, autoimmune and vasculitis diseases in children]. [2011]

7. United States pubmed.ncbi.nlm.nih.gov

Polyreactive autoantibodies purified from human intravenous immunoglobulins prevent the development of experimental autoimmune diseases. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

High-dose immunoglobulin therapy as an immunomodulatory treatment of rheumatoid arthritis. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoints, a Novel Class of Therapeutic Targets for Autoimmune Diseases. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Treatment of pyoderma gangrenosum with intravenous immunoglobulin. [2008]