A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Ascending Dose and Food Effect Study to Evaluate the Tolerance, Pharmacokinetics of Jaktinib, a New Selective Janus Kinase Inhibitor in Healthy Chinese Volunteers

Liu, Jingrui; Lv, Binhua; Yin, Hewen; Zhu, Xiaodong; Wei, Haijing; Ding, Yanhua

doi:10.3389/fphar.2020.604314

Cited by 20 publications

(19 citation statements)

References 21 publications

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“…It displays similar potency to Momelotinib and Ruxolitinib [193]. Jaktinib suppresses Jakl, Jak2, Jak3 and Tyk2 at the cellular level, inhibits the Jak-Stat signaling pathways to block the release of cytokines, including IL-2, IL-4, IL-6, IL-7 and IL-10, and significantly relieves inflammation due to immune reactions [193]. Preclinical toxicology studies conducted in Wistar rats and Beagle dogs with oral administration of Jaktinib showed no observed AEs [193].…”

Section: Jaktinib (Suzhou Zelgen Biopharmaceuticals)mentioning

confidence: 93%

“…Jaktinib is an oral and potent Jak1/2 inhibitor with an IC50 of 0.1 µM based on a cellfree kinase assay (Table 1). It displays similar potency to Momelotinib and Ruxolitinib [193]. Jaktinib suppresses Jakl, Jak2, Jak3 and Tyk2 at the cellular level, inhibits the Jak-Stat signaling pathways to block the release of cytokines, including IL-2, IL-4, IL-6, IL-7 and IL-10, and significantly relieves inflammation due to immune reactions [193].…”

Section: Jaktinib (Suzhou Zelgen Biopharmaceuticals)mentioning

confidence: 99%

“…Jaktinib suppresses Jakl, Jak2, Jak3 and Tyk2 at the cellular level, inhibits the Jak-Stat signaling pathways to block the release of cytokines, including IL-2, IL-4, IL-6, IL-7 and IL-10, and significantly relieves inflammation due to immune reactions [193]. Preclinical toxicology studies conducted in Wistar rats and Beagle dogs with oral administration of Jaktinib showed no observed AEs [193]. Currently, Jaktinib is in phase II clinical trials for idiopathic pulmonary fibrosis (NCT 04312594), primary MF (NCT 04217993, NCT 03886415) and alopecia areata (NCT 04435392, NCT 04445363).…”

Section: Jaktinib (Suzhou Zelgen Biopharmaceuticals)mentioning

confidence: 99%

“…Currently, Jaktinib is in phase II clinical trials for idiopathic pulmonary fibrosis (NCT 04312594), primary MF (NCT 04217993, NCT 03886415) and alopecia areata (NCT 04435392, NCT 04445363). A recent study indicated that Jaktinib has the potential to inhibit the proliferation of SARS-CoV-2 in vivo by inhibiting adapter associated kinase-1 (AAK1) activity, virus replication and cytokine storms to potentially delay disease progression, thereby reducing the mortality of COVID-19 [193].…”

Section: Jaktinib (Suzhou Zelgen Biopharmaceuticals)mentioning

confidence: 99%

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Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

Beinhoff

Sabharwal

Udhane

et al. 2021

Cancers

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Androgen deprivation therapy (ADT) for metastatic and high-risk prostate cancer (PC) inhibits growth pathways driven by the androgen receptor (AR). Over time, ADT leads to the emergence of lethal castrate-resistant PC (CRPC), which is consistently caused by an acquired ability of tumors to re-activate AR. This has led to the development of second-generation anti-androgens that more effectively antagonize AR, such as enzalutamide (ENZ). However, the resistance of CRPC to ENZ develops rapidly. Studies utilizing preclinical models of PC have established that inhibition of the Jak2-Stat5 signaling leads to extensive PC cell apoptosis and decreased tumor growth. In large clinical cohorts, Jak2-Stat5 activity predicts PC progression and recurrence. Recently, Jak2-Stat5 signaling was demonstrated to induce ENZ-resistant PC growth in preclinical PC models, further emphasizing the importance of Jak2-Stat5 for therapeutic targeting for advanced PC. The discovery of the Jak2V617F somatic mutation in myeloproliferative disorders triggered the rapid development of Jak1/2-specific inhibitors for a variety of myeloproliferative and auto-immune disorders as well as hematological malignancies. Here, we review Jak2 inhibitors targeting the mutated Jak2V617F vs. wild type (WT)-Jak2 that are currently in the development pipeline. Among these 35 compounds with documented Jak2 inhibitory activity, those with potency against WT-Jak2 hold strong potential for advanced PC therapy.

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Section: Jaktinib (Suzhou Zelgen Biopharmaceuticals)mentioning

confidence: 93%

Section: Jaktinib (Suzhou Zelgen Biopharmaceuticals)mentioning

confidence: 99%

Section: Jaktinib (Suzhou Zelgen Biopharmaceuticals)mentioning

confidence: 99%

Section: Jaktinib (Suzhou Zelgen Biopharmaceuticals)mentioning

confidence: 99%

See 2 more Smart Citations

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

Beinhoff

Sabharwal

Udhane

et al. 2021

Cancers

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“…Jaktinib (Suzhou Zelgen Biopharmaceuticals Co., Ltd.) is a twice-daily, oral selective JAK1/2 inhibitor currently in phase II development for psoriasis (Table 2) [61]. The drug was Pustulosis Area and Severity Index, mNAPSI Modified Nail Psoriasis Severity Index investigated in a phase I single ascending dose (SAD), multiple ascending dose (MAD), and food effect study and was found to be well tolerated among healthy Chinese participants [61].…”

Section: Janus Kinase Inhibitorsmentioning

confidence: 99%

A Review of the Clinical Trial Landscape in Psoriasis: An Update for Clinicians

Drakos

Vender

2022

Dermatol Ther (Heidelb)

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As our understanding of the pathogenesis of psoriasis has evolved over the past two decades, so has the number of treatment options. The introduction of biologic agents targeting specific cytokines in the interleukin (IL)-23/IL-17 pathway has proven successful in promoting skin clearance among patients. However, their use is often limited owing to cost, parenteral administration, and possible reduced efficacy over time. Topical therapies have also seen limited advancement, with agents such as corticosteroids and vitamin D derivatives remaining the mainstay of treatment, despite side effects limiting their long-term use. New therapeutic agents are needed to improve disease management for patients. In this review, we summarize pipeline and recently approved therapies undergoing clinical trials for psoriasis during a 12-month search period (30 June 2021 to 30 June 2022) using ClinicalTrials.gov. New-generation biologics and oral small molecules in phase II or III development were included, and pivotal data identified through various search modalities (PubMed, conference presentations, etc.) evaluating each drug candidate will be discussed. Topical therapies will also be discussed in line with recent US Food and Drug Administration approvals. As new therapies continue to enter the treatment landscape, long-term data and comparative trials will be needed to better understand their place among existing therapeutic agents.

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Safety and efficacy of jaktinib in the treatment of Janus kinase inhibitor‐naïve patients with myelofibrosis: Results of a phase II trial

et al. 2022

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Myelofibrosis (MF) is associated with several constitutional symptoms. Currently, there are few therapeutic options for MF. Jaktinib, a novel, small-molecule inhibitor of JAK, is currently being studied for its potential to treat MF. This phase 2 trial investigated efficacy and safety of jaktinib in the treatment of MF patients. The primary end point was the proportion of patients with ≥35% reduction in spleen volume (SVR35, proportion of patients with ≥35% reduction in spleen volume) at week 24. The secondary end points included improvement of anemia, rates of symptom response, and safety profile. Between January 8, 2019 and August 29, 2020, 118 patients were recruited and treated with either jaktinib 100 mg BID or 200 mg QD. At week 24, 54.8% (34/62) of patients in the 100 mg BID group and 31.3% (15/48) in the 200 mg QD group achieved SVR35 (p = .0199). Jaktinib treatment increased hemoglobin level to ≥20 g/L in 35.6% (21/59) of patients with hemoglobin ≤100 g/L at baseline. The proportion of patients who achieved a ≥50% improvement in total symptom score at week 24 was 69.6% (39/56) in the BID group and 57.5% (23/40) in the QD group. The most common ≥ grade 3 hematological treatment-emergent adverse events (TEAEs; ≥ 10%) were anemia (100 mg BID: 24.2%, 200 mg QD: 28.8%), thrombocytopenia (16.7%, 11.5%), and neutropenia (3.0%, 11.5%). All non-hematological TEAEs were mild. These results indicate that jaktinib can shrink the spleen, improve anemia, and other clinical symptoms with good tolerability.

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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Ascending Dose and Food Effect Study to Evaluate the Tolerance, Pharmacokinetics of Jaktinib, a New Selective Janus Kinase Inhibitor in Healthy Chinese Volunteers

Cited by 20 publications

References 21 publications

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

A Review of the Clinical Trial Landscape in Psoriasis: An Update for Clinicians

Safety and efficacy of jaktinib in the treatment of Janus kinase inhibitor‐naïve patients with myelofibrosis: Results of a phase II trial

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