Ianalumab + Eltrombopag for Low Platelet Count

(VAYHIT2 Trial)

Recruiting at 105 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Novartis Pharmaceuticals

Must be taking: Eltrombopag

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: HIV, Hepatitis, Coagulation disorders, others

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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 adults with primary ITP who failed previous first-line treatment with steroids.

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).

How is the drug combination of Ianalumab and Eltrombopag unique for treating low platelet count?

The combination of Ianalumab and Eltrombopag is unique because it combines a monoclonal antibody (Ianalumab) with a thrombopoietin receptor agonist (Eltrombopag), potentially offering a novel approach to stimulate platelet production and modulate the immune system, which may differ from standard treatments that typically focus on one mechanism. ^{1 2 3 4 5}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

I am 18 years or older.

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.

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.

Trial Timeline

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

Treatment Details

Interventions

• Eltrombopag (Thrombopoietin Receptor Agonist)
• Ianalumab (Monoclonal Antibodies)
• Placebo (Drug)

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.

Participant Groups

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 Canada, Japan, China for the following indications:

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

Findings from Research

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Tremelimumab: First Approval. [2023]

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

Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. [2022]

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

A Review of Tisotumab Vedotin-tftv in Recurrent or Metastatic Cervical Cancer. [2023]

4. New Zealand 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. [2023]

5. Germany 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. [2021]