TAK-279 for Psoriasis

Recruiting at 351 trial locations

Overseen By Dena Petersen

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Must not be taking: Biologics, TNF inhibitors

Disqualifiers: Non-plaque psoriasis, Cancer, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

1300 Participants Needed

Trial Summary

What is the purpose of this trial?

The main aim of this study is to check the side effects of TAK-279 and how well it is tolerated in participants with moderate-to-severe plaque psoriasis. All participants will be assigned to study treatments of TAK-279 and will be treated with TAK-279 if the participants meet the study rules. Participants will be in the study for up to 217 weeks, including up to 35 days for the screening period, 52 weeks (Part A) up to 156 additional weeks (Part B) study treatment and 4 weeks follow up period. During the study, participants will visit their study clinic multiple times.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that certain biologics and immune therapies should not have been used within specific time frames before starting the trial. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the drug TAK-279 for treating psoriasis?

Research on similar drugs, like deucravacitinib, which also inhibit TYK2, shows they can be effective in treating moderate-to-severe plaque psoriasis. These drugs work by targeting specific pathways involved in the disease, potentially offering benefits with fewer side effects. ^{1 2 3 4 5}

Is TAK-279 safe for humans?

Deucravacitinib, a similar TYK2 inhibitor, was found to be well tolerated and safe in clinical trials for psoriasis, with no serious infections or major side effects reported. ^{1 6 7 8 9}

What makes the drug TAK-279 unique for treating psoriasis?

TAK-279 is a small molecule TYK2 inhibitor, which is a novel approach for treating psoriasis by specifically targeting the TYK2 enzyme involved in the immune response, potentially offering a more targeted treatment compared to traditional therapies. ^{10 11 12 13 14}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for adults over 18 with chronic plaque psoriasis for at least 6 months, covering more than 10% of their body. They must be stable, without significant changes in their condition recently and be candidates for phototherapy or systemic therapy. Participants need to understand the study procedures and agree to follow them.

Inclusion Criteria

I have been diagnosed with chronic plaque psoriasis for at least 6 months.

Main

My psoriasis has been stable without major changes for at least 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Treatment Part A

Participants receive TAK-279, oral tablet once daily for up to 52 weeks

52 weeks

Multiple visits (in-person)

Treatment Part B

Participants who complete Part A or parent studies receive TAK-279, oral tablet once daily for up to 156 weeks

156 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TAK-279

Trial Overview The trial tests TAK-279's safety and effectiveness in those with moderate-to-severe plaque psoriasis. It involves up to 217 weeks of treatment including a screening period, an initial treatment phase (Part A), an optional extended phase (Part B), and a follow-up.

Participant Groups

Group I: Part A (De Novo Cohort) + Part B (Open Label Extension): TAK-279 Experimental Treatment 1 Intervention

Part A: Participants will receive TAK-279, oral tablet once daily (QD) for up to 52 weeks. Part B: Participants who completed the treatment period of parent studies (TAK-279-3001 \[NCT06088043\] or TAK-279-3002 \[NCT06108544\]) or who completed Part A will receive TAK-279, oral tablet QD for up to 156 weeks.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

In a phase IIa study involving 212 patients with moderate-to-severe plaque psoriasis, the oral TYK2/Jak1 inhibitor PF-06700841 showed significant improvements in psoriasis severity, with the 30 mg once daily dose achieving the greatest reduction in PASI score at week 12.

The treatment was generally well tolerated, with no cases of herpes zoster or major cardiac events reported, although some patients experienced adverse events leading to discontinuation of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TYK2/JAK1 Inhibitor PF-06700841 in Patients with Plaque Psoriasis: Phase IIa, Randomized, Double-Blind, Placebo-Controlled Trial. Forman, SB., Pariser, DM., Poulin, Y., et al.[2021]

Deucravacitinib, a new oral drug that selectively inhibits TYK2, showed significant efficacy in treating moderate-to-severe psoriasis, with over 50% of patients achieving PASI75 at week 16 in two phase 3 trials involving 1688 participants.

The drug was well tolerated with no serious infections or significant side effects reported, indicating a favorable safety profile that could make it a promising option for patients requiring systemic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deucravacitinib in the treatment of psoriasis. Estevinho, T., Lé, AM., Torres, T.[2023]

Deucravacitinib, an oral TYK2 inhibitor, demonstrated significant efficacy in treating moderate to severe plaque psoriasis, with 65.1% of patients achieving a PASI 75 response at week 16 across 6 clinical trials involving 2248 subjects.

The safety profile of deucravacitinib is favorable, with mild adverse events like nasopharyngitis being common, and serious adverse events occurring in only 1.35% to 9.5% of patients, making it a potentially less burdensome treatment option compared to injectable therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deucravacitinib: The First FDA-Approved Oral TYK2 Inhibitor for Moderate to Severe Plaque Psoriasis. Truong, TM., Pathak, GN., Singal, A., et al.[2023]

In a long-term study involving 674 patients, deucravacitinib showed significantly higher efficacy than adalimumab, with 67.2% of patients achieving a 75% reduction in psoriasis severity (PASI 75) at 112 weeks compared to 54.0% for adalimumab.

Deucravacitinib maintained stable response rates over two years, while adalimumab's effectiveness declined, suggesting that deucravacitinib may offer a more consistent long-term treatment option for moderate-to-severe plaque psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Comparison of the Long-Term Efficacy of Deucravacitinib Versus Adalimumab for Moderate to Severe Plaque Psoriasis. Armstrong, AW., Park, SH., Patel, V., et al.[2023]

In a phase 2 trial involving 267 adults with moderate-to-severe psoriasis, the TYK2 inhibitor BMS-986165 showed significant efficacy, with up to 75% of patients achieving a 75% reduction in psoriasis severity at doses of 3 mg daily and higher compared to placebo.

While the treatment was effective, there were some safety concerns, including three serious adverse events and one case of malignant melanoma, highlighting the need for further research on the long-term safety and effectiveness of BMS-986165.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. Papp, K., Gordon, K., Thaçi, D., et al.[2021]

The study identified three significant genetic variants in the TYK2 gene associated with psoriasis, particularly highlighting the I684S variant, which is predicted to negatively affect TYK2 function.

Individuals with the protective I684S variant showed significantly lower levels of phosphorylated STAT4 (p-STAT4) in immune cells, suggesting that this variant may reduce the inflammatory response linked to psoriasis susceptibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The psoriasis-protective TYK2 I684S variant impairs IL-12 stimulated pSTAT4 response in skin-homing CD4+ and CD8+ memory T-cells. Enerbäck, C., Sandin, C., Lambert, S., et al.[2019]

Deucravacitinib, a new oral drug that selectively inhibits TYK2, demonstrated significant efficacy in treating moderate-to-severe psoriasis, with over 50% of patients achieving a 75% reduction in psoriasis symptoms (PASI75) after 16 weeks, outperforming both placebo and the active comparator apremilast.

The drug was well tolerated with a favorable safety profile, showing no serious infections or other significant adverse effects commonly associated with other JAK inhibitors, and maintained its efficacy and safety over a 52-week period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deucravacitinib for the Treatment of Psoriatic Disease. Lé, AM., Puig, L., Torres, T.[2022]

TYK2 is a crucial component of the JAK-STAT signaling pathway, which is involved in immune responses and the development of inflammatory diseases like psoriasis.

Small-molecule TYK2 inhibitors are being explored as effective treatments for psoriasis, targeting the inflammatory processes mediated by TYK2 to help manage the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TYK2 in Immune Responses and Treatment of Psoriasis. Shang, L., Cao, J., Zhao, S., et al.[2022]

Deucravacitinib, an allosteric inhibitor of Tyk2, has been approved for treating moderate-to-severe psoriasis, showcasing its efficacy and safety profile compared to traditional therapies.

Tyk2 dysfunction is linked to protection against immune-mediated inflammatory diseases (IMIDs) without increasing the risk of serious infections, making Tyk2 a promising target for new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyk2 Targeting in Immune-Mediated Inflammatory Diseases. Rusiñol, L., Puig, L.[2023]

The phase I study involving 41 patients with mild to moderate plaque psoriasis showed that topical icotinib hydrochloride cream is safe and well-tolerated, with most adverse events being mild and resolving during follow-up.

Icotinib cream demonstrated preliminary efficacy in improving psoriasis severity, with the 2.0% concentration showing the best results, suggesting it is a promising candidate for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of Icotinib Hydrochloride Cream in Patients with Mild to Moderate Chronic Plaque Psoriasis: A Randomized Double-Blind Vehicle-Controlled Phase 1 Study. Liu, L., Lou, H., Zhou, J., et al.[2022]

TAK-632, a selective pan-RAF inhibitor, effectively suppresses RAF activity in BRAF wild-type melanoma cells with minimal RAF paradoxical activation, addressing a significant clinical challenge in treating these patients.

In preclinical models, TAK-632 shows potent antiproliferative effects on both NRAS-mutated melanoma cells and BRAF-mutated cells that have developed resistance to BRAF inhibitors, especially when combined with the MEK inhibitor TAK-733, suggesting a promising new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of the selective pan-RAF inhibitor TAK-632 in BRAF inhibitor-resistant melanoma. Nakamura, A., Arita, T., Tsuchiya, S., et al.[2013]

The MEK inhibitor AZD6244 shows cytostatic effects on melanoma cells, meaning it can stop their growth without killing them, particularly in two-dimensional cultures and three-dimensional spheroid models.

When combined with the chemotherapy drug docetaxel, AZD6244 can lead to tumor regression, suggesting that using MEK inhibitors alongside traditional chemotherapy may enhance treatment effectiveness for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Haass, NK., Sproesser, K., Nguyen, TK., et al.[2018]

AZD6244, a selective MEK1/2 inhibitor, effectively reduces P-MAPK levels in melanoma cells but shows limited clinical responses, indicating a need to understand resistance mechanisms better.

Resistance to AZD6244 in Braf-mutant melanoma cells is linked to the activation of the PI3K-AKT pathway, and combining AZD6244 with inhibitors of this pathway may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Basal and treatment-induced activation of AKT mediates resistance to cell death by AZD6244 (ARRY-142886) in Braf-mutant human cutaneous melanoma cells. Gopal, YN., Deng, W., Woodman, SE., et al.[2021]

Researchers identified STK19 as a novel activator of NRAS, which is mutated in 20%-30% of melanomas, and found that a specific mutation (D89N) in STK19 enhances NRAS activity, promoting melanoma development.

The development of a targeted inhibitor, ZT-12-037-01, shows promise in blocking NRAS-driven malignant transformation and melanoma growth, suggesting a new therapeutic approach for treating melanomas with NRAS mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Targeting of STK19 Inhibits Oncogenic NRAS-Driven Melanomagenesis. Yin, C., Zhu, B., Zhang, T., et al.[2021]

References

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

TYK2/JAK1 Inhibitor PF-06700841 in Patients with Plaque Psoriasis: Phase IIa, Randomized, Double-Blind, Placebo-Controlled Trial. [2021]

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

Deucravacitinib in the treatment of psoriasis. [2023]

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

Deucravacitinib: The First FDA-Approved Oral TYK2 Inhibitor for Moderate to Severe Plaque Psoriasis. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Comparison of the Long-Term Efficacy of Deucravacitinib Versus Adalimumab for Moderate to Severe Plaque Psoriasis. [2023]

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

Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

The psoriasis-protective TYK2 I684S variant impairs IL-12 stimulated pSTAT4 response in skin-homing CD4+ and CD8+ memory T-cells. [2019]

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

Deucravacitinib for the Treatment of Psoriatic Disease. [2022]

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

TYK2 in Immune Responses and Treatment of Psoriasis. [2022]

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

Tyk2 Targeting in Immune-Mediated Inflammatory Diseases. [2023]

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

Pharmacokinetics and Safety of Icotinib Hydrochloride Cream in Patients with Mild to Moderate Chronic Plaque Psoriasis: A Randomized Double-Blind Vehicle-Controlled Phase 1 Study. [2022]

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

Antitumor activity of the selective pan-RAF inhibitor TAK-632 in BRAF inhibitor-resistant melanoma. [2013]

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

The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. [2018]

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

Basal and treatment-induced activation of AKT mediates resistance to cell death by AZD6244 (ARRY-142886) in Braf-mutant human cutaneous melanoma cells. [2021]

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

Pharmacological Targeting of STK19 Inhibits Oncogenic NRAS-Driven Melanomagenesis. [2021]