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