Phase II Study of Hemay005 in Patients With Active Ankylosing Spondylitis

Brief Title

Phase II Study of Hemay005 in Patients With Active Ankylosing Spondylitis

Official Title

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Study on the Efficacy and Safety of hemay005 Tablets in the Treatment of Active Ankylosing Spondylitis

Brief Summary

      This study is a multicenter, randomized, double-blind, placebo-controlled phase II clinical
      study. The study was divided into three stages, including screening period, treatment period
      and observation period. All subjects need to enter a 28 day (4-week) observation period after
      stopping hemay005 treatment.

      Screening period: all subjects shall have a screening period of no more than 28 days (4
      weeks) before the baseline visit (day 1 of randomization).

      Treatment period: after screening and meeting the inclusion requirements of the study, as
      subjects were randomly divided into hemay005 60 mg twice daily (bid) dose group (group A), 75
      mg bid dose group (group B) and placebo control group (Group C) according to the ratio of
      1:1:1. A total of 90 subjects were included in the three groups. They were titrated in the
      first 6 days. From the 7th day, the subjects received fixed dose administration twice a day
      for 112 consecutive days (16 weeks). Considering the difference in the proportion of men and
      women with as, and the slow onset and mild condition of women, randomization will minimize
      the imbalance between treatment groups according to gender stratification.

      Observation period: Subjects in the study (including those who withdrew from the treatment
      early for any reason) shall be observed for 4 weeks after the end of the last administration.

      Main purpose:

      The efficacy of hemay005 tablet in the treatment of active ankylosing spondylitis (as) was
      evaluated by placebo parallel control.

      Secondary purpose:

        -  To evaluate the safety of oral hemay005 tablets in patients with active as.

        -  To evaluate the population pharmacokinetics of hemay005 tablets in patients with active
           as.
    

Detailed Description

      This study is a multicenter, randomized, double-blind, placebo-controlled phase II clinical
      study. The study was divided into three stages, including screening period, treatment period
      and observation period. All subjects need to enter a 28 day (4-week) observation period after
      stopping hemay005 treatment.

      Screening period: all subjects shall have a screening period of no more than 28 days (4
      weeks) before the baseline visit (day 1 of randomization).

      Treatment period: after screening and meeting the inclusion requirements of the study, as
      subjects were randomly divided into hemay005 60 mg twice daily (bid) dose group (group A), 75
      mg bid dose group (group B) and placebo control group (Group C) according to the ratio of
      1:1:1. A total of 90 subjects were included in the three groups. They were titrated in the
      first 6 days. From the 7th day, the subjects received fixed dose administration twice a day
      for 112 consecutive days (16 weeks). Considering the difference in the proportion of men and
      women with as, and the slow onset and mild condition of women, randomization will minimize
      the imbalance between treatment groups according to gender stratification.

      Observation period: Subjects in the study (including those who withdrew from the treatment
      early for any reason) shall be observed for 4 weeks after the end of the last administration.

      Main purpose:

      The efficacy of hemay005 tablet in the treatment of active ankylosing spondylitis (as) was
      evaluated by placebo parallel control.

      Secondary purpose:

        -  To evaluate the safety of oral hemay005 tablets in patients with active as.

        -  To evaluate the population pharmacokinetics of hemay005 tablets in patients with active
           as.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

ASAS20

Secondary Outcome

 BASFI

Condition

Active Ankylosing Spondylitis

Intervention

Hemay005

Study Arms / Comparison Groups

 Hemay005 75mg BID group
Description:  75mg BID of Hemay005; daily oral administrtion for 16 weeks

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

90

Start Date

June 24, 2022

Completion Date

December 23, 2023

Primary Completion Date

November 23, 2023

Eligibility Criteria

        Inclusion Criteria:

          -  Understand and voluntarily sign the informed consent form of this study.

          -  Aged between 18 and 65 years old (both ends included, subject to the date of signing
             the informed consent form), male or female.

          -  50 kg ≤ male weight <100 kg, 45 kg ≤ female weight <100 kg.

          -  The results of human leucocyte antigen (HLA) -b27 were positive.

          -  Be able to comply with the follow-up schedule and other protocol requirements

          -  As (revised New York standard 1984) was diagnosed as follows:

               1. Low back pain lasted for at least 3 months. The pain improved with activity, but
                  the rest did not reduce;

               2. The movement of lumbar vertebra in the direction of anteroposterior and lateral
                  flexion was limited;

               3. The extension range of thorax was smaller than the normal value of the same age
                  and sex;

               4. Bilateral sacroiliac arthritis grade II ~ IV, or unilateral sacroiliac arthritis
                  grade III ~ IV.

        If the patient has 4) and adds any one of 1) ~3) respectively, it can be diagnosed as as;

          -  The subjects shall at least meet the requirements of 1) and 2) below:

               1. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, and chronic low
                  back pain ≥ 4 (patient back pain intensity assessment question 1) (NRS score);

               2. At least one nonsteroidal anti-inflammatory drugs (NSAIDs) was used before
                  randomization, but the symptoms were not relieved or the drugs were intolerable
                  or there were drug contraindications, that is, at least 4 weeks of stable use of
                  1 NSAID at the recommended dose or ≥ 2 NSAIDs, each NSAID was used stably for ≥ 2
                  weeks) or intolerable before randomization;

               3. In case of any of the following three criteria, the subject shall also meet the
                  corresponding provisions:

               1. Patients who are receiving NSAIDs, oral glucocorticoids (prednisone with daily
                  oral glucocorticoid dose ≤ 10 mg or other equivalent dose) and / or
                  cyclooxygenase-2 (COX-2) inhibitors, the dosage is stable at least 14 days before
                  randomization and throughout the study period;

               2. For patients with combined use of sulfasalazine: subjects who began to take
                  sulfasalazine [≤ 3 g/ day] at least 12 weeks before randomization and whose dose
                  and route of administration have been stable for at least 4 weeks before
                  randomization can continue to take sulfasalazine at a sustained dose during the
                  study period;

               3. For previous use of tumor necrosis factor (TNF)- α Patients with inhibitors: TNF
                  α Subjects with inhibitors did not respond adequately to the approved dose for at
                  least 12 weeks, or did not tolerate the treatment;

          -  The following laboratory standards must be met:

        Hemoglobin (HB) ≥ 9 g/dl Hematocrit ≥ 27% White blood cell (WBC) count ≥ 3000/ μ L(≥3.0 ×
        109/l) and <20000/ μ L(<20 × 109/L) Neutrophil (neu) ≥ 1500/ μ L(≥1.5 × 109/L) Platelet
        (PLT) ≥ 100000/ μ L(≥100 × 109/L) Serum creatinine (CR) ≤ 1.5 mg/dl (≤ 132.6 μ mol/L) Total
        bilirubin (TBIL) ≤ 2.0 mg/dl Aspartate aminotransferase, AST (serum glutamic oxaloacetic
        transaminase, SGOT) and alanine aminotransferase, ALT (serum glutamic pyruvic transaminase,
        SGPT)] ≤ 1.5 times the upper limits of normal (ULN);

        • During the whole study period since the signing of the informed consent and within 3
        months after the last administration of the study drug, Female subjects with fertility and
        male subjects without vasectomy are willing to take effective contraceptive measures
        [effective contraceptive measures include vasectomy, abstinence, intrauterine device (IUD),
        hormones (oral, patch, ring, injection, implantation) and barrier method (diaphragm,
        cervical cap, sponge, condom)]; The serum pregnancy test [human chorionic gonadotropin
        (hCG)] of fertile female subjects within the first 7 days of randomization must be
        negative; Male subjects could not donate sperm within 3 months after the first
        administration of the study drug to the last Administration [Note: fertility is defined as:
        non menopausal women who have experienced menarche, have not undergone sterilization
        (hysterectomy / bilateral oophorectomy / bilateral tubal ligation), and have undergone
        sterilization but have not completed 6 months (menopause refers to continuous natural
        menopause ≥ 12 months)].

        Exclusion Criteria:

          -  Have the following diseases or disease history:

               1. Complete rigidity of spine or complete fusion of sacroiliac joint;

               2. Patients with a history of other rheumatic autoimmune diseases (such as systemic
                  lupus erythematosus, rheumatoid arthritis, etc.);

               3. Patients with a history of tuberculosis or active tuberculosis (there are signs
                  or symptoms of active tuberculosis judged by the researcher at the time of
                  screening):

                  If the patient has a previous history of tuberculosis and has been cured for at
                  least 3 years before randomization according to the researcher's assessment,
                  screening is allowed; Subjects with negative T-SPOT during screening can be
                  included in this study. Subjects with positive T-SPOT in the screening period
                  need to undergo tuberculosis related clinical examination (tuberculosis related
                  clinical examination conducted within 12 weeks before randomization can be
                  directly used for evaluation). If tuberculosis related clinical examination is
                  confirmed as active tuberculosis, subjects cannot be selected for this study; If
                  tuberculosis related clinical examination confirms inactive tuberculosis, the
                  subject can be included in this study. If the research center is unable to carry
                  out T-SPOT test, it can also accept tuberculosis screening with QuantiFERON TB
                  gold test kit. The processing of QuantiFERON TB gold screening results is the
                  same as that of T-SPOT;

               4. Patients with malignant tumor or any history of malignant tumor within 5 years
                  before screening (except skin squamous cell carcinoma in situ, basal cell
                  carcinoma or cervical carcinoma in situ after treatment and no recurrence
                  evidence in the past 12 weeks);

               5. Evidence of active infection within 1 month before screening, including acute and
                  chronic infection and local infection, such as sepsis, abscess, cellulitis and
                  opportunistic fungal (such as Candida) infection (which can be judged by the
                  research doctor in combination with the specific situation of the patient);

               6. Patients with severe basic diseases, such as heart, lung, kidney, liver, nerve,
                  endocrine, gastrointestinal, metabolic or hematological diseases, moderate to
                  severe congestive heart failure (New York Heart Association grade III or IV);

               7. Have a history of alcohol or drug abuse or dependence, or a history of mental
                  illness;

               8. Situations that may affect the absorption of oral drugs, such as subtotal
                  gastrectomy, clinically significant diabetes gastroenteropathy, or some types of
                  weight loss surgery such as gastric bypass surgery, do not include operations
                  that simply partition the stomach into a separate chamber, such as gastric
                  banding surgery;

          -  Pregnant or lactating women;

          -  Those who are allergic or allergic to the study drug or its preparation components;

          -  Those who have undergone major surgery (including spinal surgery or joint surgery)
             within the first 6 months or plan to undergo major surgery during the trial;

          -  Those who have participated in clinical trials of any drugs or medical devices within
             the first three months of screening;

          -  Those who plan to receive attenuated or live vaccine during the test;

          -  Taking or having the following medication history:

               1. Patients who used disease modifying anti rheumatic drugs (DMARDs) methotrexate,
                  penicillamine, sulfasalazine, azathioprine and hydroxychloroquine within the
                  first 4 weeks of randomization, except those who used sulfasalazine at a stable
                  dose, and other unlisted abiotic agents were eluted according to 5 drug half
                  lives (or 4 weeks, whichever is longer);

               2. Intravenous or articular endothelium steroids were used within the first 4 weeks
                  of randomization;

               3. Etanercept, adalimumab, efuzumab, infliximab and afacept were used within 8 weeks
                  before randomization, and other unlisted biological agents were eluted according
                  to 5 drug half lives (or 8 weeks, whichever is longer);

               4. Those who used apster before randomization;

               5. Those who used strong cytochrome P450 enzyme inducers within 4 weeks before
                  randomization (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin sodium);

               6. Those who used Tripterygium Wilfordii and other proprietary Chinese medicine or
                  traditional Chinese medicine decoction within 2 weeks before randomization;

          -  There are any clinically significant abnormalities in 12 lead ECG at the time of
             screening, and the researcher assessed that participating in this study may increase
             the risk of subjects or interfere with data interpretation;

          -  Patients with clinically significant abnormalities in chest X-ray (CXR) or computed
             tomography (CT) during screening, and the researchers may put the subjects at safety
             risk;

          -  subjects with positive hepatitis B B surface antigen (HBsAg), hepatitis C virus
             antibody (HCVAb), human immunodeficiency virus antibody (hivab) or Treponema pallidum
             antibody;

          -  Have committed suicide (including active attempt, interrupted attempt or attempted
             attempt) or have suicidal thoughts in the past 6 months;

          -  The researcher believes that there are any other circumstances that are not suitable
             for participating in the trial.
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Xiaofeng Zeng, M.D, 86-22-24929667, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT05407246

Organization ID

HM005AS2S01


Responsible Party

Sponsor

Study Sponsor

Tianjin Hemay Pharmaceutical Co., Ltd


Study Sponsor

Xiaofeng Zeng, M.D, Principal Investigator, Peking Union Medical College


Verification Date

June 2022