Ianalumab + Eltrombopag for Low Platelet Count

(VAYHIT2 Trial)

Not currently recruiting at 127 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Eltrombopag

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: HIV, Hepatitis, Coagulation disorders, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding ianalumab (an experimental treatment) to eltrombopag can benefit people with primary ITP, a condition where the immune system attacks and destroys platelets, causing low platelet counts. The goal is to determine if this combination can delay the need for further treatment after steroids have failed. Participants will receive eltrombopag with either a lower dose of ianalumab, a higher dose, or a placebo. Suitable candidates have primary ITP, did not respond well to initial steroid treatment, and have a low platelet count. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on antiplatelet or anticoagulant medications, you may need to stop them unless it's a low dose of acetylsalicylic acid (up to 150 mg daily).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of ianalumab and eltrombopag is being tested to help people with low platelet counts, especially those unresponsive to steroids. Earlier studies have shown positive results, with the treatment maintaining safe platelet levels for a longer time, which is crucial for managing the condition.

The safety of these treatments remains a key focus. Eltrombopag is already approved for increasing platelet counts in other conditions, indicating it is generally well-tolerated. Initial findings with ianalumab are also promising, showing it can be safely used with eltrombopag. Although the studies did not detail specific side effects, researchers are closely monitoring the treatments to ensure safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Ianalumab combined with Eltrombopag for addressing low platelet count because this combination targets the issue in a novel way. While standard treatments, like corticosteroids or intravenous immunoglobulin, often focus on boosting platelet production indirectly, Ianalumab is an antibody that directly modifies the immune response, potentially leading to a more stable increase in platelet levels. Eltrombopag, a thrombopoietin receptor agonist, stimulates platelet production directly. Together, these treatments may offer a more effective and potentially faster approach to increasing platelet counts than existing options, with the added benefit of potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for low platelet count?

In this trial, participants will receive different combinations of treatments to address low platelet counts. Earlier studies have shown that the combination of ianalumab and eltrombopag holds promise for treating primary immune thrombocytopenia (ITP), a condition where low platelet levels can cause bruising and bleeding. Research indicates that ianalumab helped patients maintain safe platelet levels for longer, reducing the need for additional treatments. This suggests that adding ianalumab to eltrombopag could help stabilize platelet counts for extended periods. These findings support the potential effectiveness of the treatment for individuals who haven't responded well to steroid treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults over 18 with primary immune thrombocytopenia (ITP) who didn't respond well to steroids can join. They must have a low platelet count and be eligible for eltrombopag treatment. People with coagulation disorders, other cytopenias, significant blood diseases, life-threatening bleeding history, or positive HIV/HCV cannot participate.

Inclusion Criteria

A signed informed consent must be obtained prior to participation in the study

My platelet count is below 30G/L and I can take eltrombopag.

I have ITP and steroids or IVIG didn't work well for me.

Exclusion Criteria

I have ITP and have tried treatments beyond steroids, including having my spleen removed.

I have a history of severe bleeding.

I have liver problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Treatment

Participants receive ianalumab or placebo in addition to eltrombopag

24 weeks

Regular visits for monitoring and dose adjustments

Eltrombopag Tapering

Participants undergo tapering of eltrombopag

Up to 24 weeks

Regular visits for monitoring tapering process

Follow-up

Participants are monitored for efficacy and safety after treatment

Up to 39 months

Periodic visits for long-term monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Eltrombopag
• Ianalumab
• Placebo

Trial Overview

The trial is testing how effective two doses of ianalumab are when added to eltrombopag in prolonging the time before ITP treatment fails after steroid therapy doesn’t work. Participants will either receive ianalumab or a placebo alongside eltrombopag.

How Is the Trial Designed?

Group I: Treatment arm 2 Experimental Treatment 2 Interventions

Participants will receive eltrombopag and ianalumab higher dose

Group II: Treatment arm 1 Experimental Treatment 2 Interventions

Participants will receive eltrombopag and ianalumab lower dose

Group III: Treatment arm 3 Placebo Group 2 Interventions

Participants will receive eltrombopag and placebo

Eltrombopag is already approved in United States, European Union, Canada, Japan, China for the following indications:

Approved in United States as Promacta for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia
• Thrombocytopenia in patients with chronic hepatitis C

Approved in European Union as Revolade for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Approved in Canada as Promacta for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Approved in Japan as Revolade for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Approved in China as Promacta for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

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

Published Research Related to This Trial

Tisotumab vedotin-tftv (TV) is a first-in-class antibody-drug conjugate that targets tissue factor and has shown a 24% objective response rate in treating recurrent or metastatic cervical cancer, with a mean duration of response of 8.3 months based on the pivotal phase II InnovaTV 204 trial.

While TV has a manageable safety profile, it is associated with common side effects like abdominal pain and nausea, as well as serious adverse events such as ocular complications and fetal-embryo toxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Tisotumab Vedotin-tftv in Recurrent or Metastatic Cervical Cancer. Heitz, N., Greer, SC., Halford, Z.[2023]

Tisotumab vedotin (TV) is the first antibody-drug conjugate targeting tissue factor in cervical cancer, showing promising results in treating recurrent or metastatic cases with a favorable safety profile and limited severe side effects.

The FDA granted expedited approval for TV based on positive preliminary data, and ongoing trials are expected to further establish its efficacy and potentially set it as a new standard of care for advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of Tisotumab Vedotin in the Treatment of Recurrent or Metastatic Cervical Cancer: A Short Report on the Emerging Data. Agostinelli, V., Musacchio, L., Camarda, F., et al.[2023]

In a phase 1b clinical trial involving 21 patients with advanced melanoma, the combination of oncolytic virotherapy using talimogene laherparepvec and the anti-PD-1 antibody pembrolizumab was well tolerated, with a 62% confirmed objective response rate and a 33% complete response rate.

The combination therapy led to increased infiltration of CD8+ T cells and elevated PD-L1 expression in tumors, suggesting that talimogene laherparepvec may enhance the effectiveness of anti-PD-1 therapy by modifying the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Ribas, A., Dummer, R., Puzanov, I., et al.[2022]

Combining anti-CTLA4 antibodies with antisense suppression of CD47 significantly enhances the immune response against melanoma, leading to improved survival rates in mouse models compared to either treatment alone.

This combination therapy increases T-cell infiltration and activity in irradiated tumors, suggesting a mechanism that boosts the effectiveness of radiotherapy by enhancing T- and NK-cell immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antisense targeting of CD47 enhances human cytotoxic T-cell activity and increases survival of mice bearing B16 melanoma when combined with anti-CTLA4 and tumor irradiation. Schwartz, AL., Nath, PR., Allgauer, M., et al.[2021]

Tremelimumab, a CTLA-4 blocking antibody, was approved in the USA in October 2022 for treating unresectable hepatocellular carcinoma (uHCC) in combination with durvalumab, marking a significant advancement in cancer therapy.

In November 2022, tremelimumab was also approved for metastatic non-small cell lung cancer (mNSCLC) when combined with durvalumab and platinum-based chemotherapy, indicating its broad potential in treating various malignant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab: First Approval. Keam, SJ.[2023]

Citations

1.

novartis.com

novartis.com/news/media-releases/novartis-ianalumab-phase-iii-trial-meets-primary-endpoint-itp-demonstrating-statistically-significant-improvement-time-treatment-failure

Novartis ianalumab Phase III trial meets primary endpoint ...

Ianalumab prolonged the duration of safe platelet levels during and after treatment in patients with primary immune thrombocytopenia (ITP) ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05653219

NCT05653219 | A Study of Efficacy and Safety ...

The purpose of this study is to evaluate the effect of two different doses of ianalumab added to eltrombopag to prolong Time to Treatment Failure (TTF) in ...

3.

docwirenews.com

docwirenews.com/post/novartis-ianalumab-phase-3-trial-shows-longer-remission-in-itp

Novartis Ianalumab Phase 3 Trial Shows Longer ...

It included recurrent low platelet counts after week 8, need for rescue therapy, starting a new ITP treatment, inability to taper or discontinue ...

4.

oncologypipeline.com

oncologypipeline.com/apexonco/novartis-scores-vayhit-filing-some-way

Novartis scores a Vayhit, but filing some way off | ApexOnco

ITP is caused by low platelet levels that can lead to bruising and bleeding; steroids are a treatment mainstay, but carry long-term risks, while ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10429596/

VAYHIT2: A RANDOMIZED, DOUBLE-BLIND, PHASE III ...

The Phase III VAYHIT2 study will evaluate the ability of ianalumab in addition to a short ETB treatment to prolong time to treatment failure.

6.

fiercebiotech.com

fiercebiotech.com/biotech/novartis-blood-disorder-readout-earns-novartis-3rd-phase-3-win-ianalumab-week

Novartis scores 3rd phase 3 win for ianalumab this week

TTF measures how long patients maintain safe platelet levels during and after treatment. When it came to a key secondary endpoint, the ianalumab ...