Jaktinib Dihydrochloride Monohydrate in Idiopathic Pulmonary Fibrosis

• ClinicalTrials.gov Identifier: NCT04312594
• Recruitment Status: Active, not recruiting
• First Posted: March 18, 2020
• Last Update Posted: March 23, 2023
• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Information provided by (Responsible Party): Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Study Description

Brief Summary:

Jaktinib Dihydrochloride Monohydrate for idiopathic pulmonary fibrosis

Condition or disease	Intervention/treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Jaktinib Dihydrochloride Monohydrate 50mg BID and Mimic tablets of jakitinib hydrochloride 75mg BID and Acetylcysteine Effervescent Tablets; Drug: Jaktinib Dihydrochloride Monohydrate 75mg BID and Mimic tablets of jakitinib hydrochloride 50mg BID and Acetylcysteine Effervescent Tablets; Drug: Placebo oral tablet and Acetylcysteine Effervescent Tablets	Phase 2

Detailed Description:

This phase 2 study of Jaktinib Dihydrochloride Monohydrate, an oral inhibitor of JAK1 、JAK2 and JAK3, is to assess efficacy and safety in patients with idiopathic pulmonary fibrosis.The study is a randomised,multicentre,double-blind,placebo-controlled,study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind,Placebo-controlled,Phase 2 Trial of Jaktinib Dihydrochloride Monohydrate in Idiopathic Pulmonary Fibrosis
• Actual Study Start Date: September 8, 2020
• Estimated Primary Completion Date: October 15, 2023
• Estimated Study Completion Date: December 15, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Jaktinib Dihydrochloride Monohydrate 50mg and Basic treatment; Jaktinib Dihydrochloride Monohydrate 50mg BID and Mimic tablets of jakitinib hydrochloride 75mg BID and basic treatment(Acetylcysteine Effervescent Tablets 600mg TID) for each 24 weeks cycle.	Drug: Jaktinib Dihydrochloride Monohydrate 50mg BID and Mimic tablets of jakitinib hydrochloride 75mg BID and Acetylcysteine Effervescent Tablets; after continuing to intolerance or progress in double blind treatment period for 24 weeks,for tolerance into open therapy period for evaluated by investigator; Other Name: treatment drug
Experimental: Jaktinib Dihydrochloride Monohydrate 75mg and Basic treatment; Jaktinib Dihydrochloride Monohydrate 75mg BID and Mimic tablets of jakitinib hydrochloride 50mg BID and basic treatment(Acetylcysteine Effervescent Tablets 600mg TID) for each 24 weeks cycle.	Drug: Jaktinib Dihydrochloride Monohydrate 75mg BID and Mimic tablets of jakitinib hydrochloride 50mg BID and Acetylcysteine Effervescent Tablets; after continuing to intolerance or progress in double blind treatment period for 24 weeks,for tolerance into open therapy period for evaluated by investigator; Other Name: treatment drug
Placebo Comparator: Placebo and Basic treatment; Mimic tablets of Jaktinib Dihydrochloride Monohydrate 50mg BID and 75mg BIDand basic treatment(Acetylcysteine Effervescent Tablets 600mg TID) for each 24 weeks cycle.	Drug: Placebo oral tablet and Acetylcysteine Effervescent Tablets; after continuing to intolerance or progress in double blind treatment period for 24 weeks,for tolerance into open therapy period for evaluated by investigator; Other Name: Placebo for Jaktinib Dihydrochloride Monohydrate

Outcome Measures

Primary Outcome Measures :

1. Changes in forced vital capacity (FVC) [ Time Frame: 24 weeks ] [ Time Frame: 24 weeks ]
   Changes in FVC from 24 weeks to baseline

Secondary Outcome Measures :

1. Progression-free time [ Time Frame: the onset of disease or death from any cause ] [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months ]
   The time from a random date to the onset of disease or death from any cause;
2. Non-worsening survival time: [ Time Frame:the time from randomization to the first acute exacerbation ]; [ Time Frame: from randomization to one month ]
   acute aggravation events should meet all the following conditions: (1) acute exacerbation or aggravation of respiratory distress within 1 month;Chest CT showed new bilateral ground glass shadows or pulmonary interstitial fibrosis with pulmonary consolidation;(3) exclude heart failure, fluid retention and infection caused by acute dyspnea
3. K-BILD Scale: absolute value of change from baseline [ Time Frame: 24 weeks ] [ Time Frame: 24 weeks ]
   absolute value of change from baseline at 24 weeks
4. mMRC Dyspnea scale：absolute value of change from baseline [ Time Frame: 24 weeks ] [ Time Frame: 24 weeks ]
   absolute value of change from baseline at 24 weeks
5. Survival rate: [ Time Frame: 6 months, 12 months, 24 months ] [ Time Frame: 6 months, 12 months, 24 months ]
   Survival rate
6. The severity and incidence of all adverse events and adverse reactions[ Time Frame: within 28 days after the signing of the informed consent] [ Time Frame: within 28 days after the signing of the informed consent ]
   The severity and incidence of all adverse events and adverse reactions

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Written informed consent signed;at least 50 years of age;no gender limitation.
2. Diagnosed idiopathic pulmonary fibrosis(see 2018.9 guidance that AST and ERS and JRS and ALAT publish );
3. FVC%≥45% normal predicted value;
4. DLCO≥30% normal predicted value；
5. FEV1 / FVC ≥0.7

Exclusion Criteria:

1. A plan of lung transplant after into group for one year.
2. In addition of IPF,Other causes cause interstitial lung disease in patients；
3. Patients with bleeding tendency (INR > 2, PT or APTT > 1.5 times normal) or cerebral hemorrhage in the past 1 year;
4. Have used anticoagulant drugs within 1 month（Except for low molecular weight heparin）;
5. An alcoholic or drug abuser;
6. Expected survival ≤ one year;
7. Patients who plan to undergo a operation within study period, such as major operations on chest and abdomen;
8. Previous use of a JAK inhibitor for more than 10 days or treatment failure;
9. Suspected allergic to Jaktinib Dihydrochloride Monohydrate , similar drugs (Fedratinib,Ruxolitinib)or their excipients;
10. Patients with malignant tumors in the previous 5 years;
11. Patients with other serious diseases that investigators believe may affect patient safety or compliance;
12. Any significant clinical or laboratory abnormalities that the investigator considers to affect safety assessment, such as: a. uncontrolled diabetes (13.9 tendency > / L), b. had high blood pressure and antihypertensive drug treatment under two or unable to descend to the ranges (systolic blood pressure < 160 mmHg, diastolic pressure < 100 mmHg), c. peripheral neuropathy (NCI - CTC AE v5.0 standard grade 2 or above)；
13. Patients hospitalized for deterioration or acute exacerbation of IPF within 1 month prior to screening;
14. patients who had not fully recovered from surgery within 1 month prior to screening;
15. Participate in clinical trials of other new drugs or medical devices within 3 months before screening;
16. Prednisone > 15mg/ day or equivalent within 1 month prior to screening;
17. Those who had used pirfenidone, nidanib, azathioprine, cyclophosphamide, cyclosporine A or other immunosuppressive drugs within 1 month prior to screening;
18. A history of congestive heart failure, uncontrolled or unstable angina or myocardial infarction, cerebrovascular accident or pulmonary embolism occurred within 6 month prior to screening;
19. Patients with active TB in the 12 months prior to screening;
20. Screening patients with arrhythmia requiring treatment, or with QTcB >480ms;
21. At the time of screening, there was evidence of severe impairment of organ function : including ALT and AST > 2.5uln;DBIL and TBIL > 2.0 ULN;Serum creatinine > was 1.5 ULN.
22. Evidence of active and uncontrolled viral infections such as HIV, HBV (HBsAg positive, hbv-dna positive or ≥10000 copies /ml), HCV (anti-hcv antibody or hcv-rna positive), or bacterial, viral, parasitic or fungal infections requiring treatment with any clinical symptoms;
23. patients with a history of progressive multifocal leukoencephalopathy in Screening ;
24. Patients with epilepsy or using antipsychotics(Sleep medicine,for diazepam expect) for treatment of mental illness( schizophrenia,depressed,mania,anxiety,and so on) at the time of screening;
25. Women who are planning to become pregnant or who are pregnant or breast-feeding and who are unable to use effective contraception throughout the trial period;Male patients who did not use condoms during administration and within 1 month after the last dose;
26. Subjects who cannot be treated and followed up according to the protocol;
27. Any subject whom the investigator considers inappropriate for this clinical study.

Contacts and Locations

Locations

China, Beijing

Peking Union Medical College Hospital

Beijing, Beijing, China, 100730

Sponsors and Collaborators

Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Investigators

• Principal Investigator: Zuojun Xu; Peking Union Medical College Hospital

More Information

• Responsible Party: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• ClinicalTrials.gov Identifier: NCT04312594
• Other Study ID Numbers: ZGJAK005
• First Posted: March 18, 2020
• Last Update Posted: March 23, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases; Acetylcysteine; N-monoacetylcystine; Antiviral Agents; Anti-Infective Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Antidotes