A Randomized, Double-blind, Placebo Self-controlled Phase I/II Clinical Study to Evaluate the Safety, Tolerability and Preventive Efficacy of AK3280 Cream After Cicatrectomy in Patients With Hypertrophic Scar in China.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of participants with abnormal 12-lead ECG readings
研究概览
简要总结
A randomized, double-blind, placebo self-controlled phase I/II clinical study to evaluate the safety, tolerability and preventive efficacy of different doses of AK3280 cream （AK3287 ） after cicatrectomy in Patients with Hypertrophic Scar in China.
详细描述
Thirty patients with hypertrophic scar who will scheduled for cicatrectomy and meet the all inclusion criteria and none of exclusion criteria will participate in this study. There will be 3 cohorts for 2%, 4%, 8% doses of AK3287 （AK3280 cream） in turn, and 10 participants in each cohort. Participants in every cohort will receive cicatrectomy on day -5, and their incisions will be divided into 3 parts with equal length after length measurement on day 1, named S1, S2, S3. S1 is proximal, and S3 is distal. AK3280 cream （AK3287 ） or placebo will topically administrated to S1 or S3 randomly, twice a day (BID). In this study, S1 and S3 paired, placebo self-control design will be adopted.
The study includes a 4-week screening period, a 12-week drug observation period, and a 2-week safety follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1) Patients who sign informed consent before participating in the study.
- •2) Patients aged between 18 and 60 (including 18 and 60).
- •Patients who understand and be willing to follow the study procedure and be able to complete the whole process of the study.
- •4) Patients with visible hypertrophic scars in any location other than the face and anterior middle and upper neck caused by trauma or surgery and planned for surgical treatment.
- •5) Patients with postoperative scar length ≥ 6 cm, and preoperative scar length ≥4cm.
- •6) Women of childbearing age should have negative serum pregnancy test during screening period and on study day 1.
排除标准
- •1) Patients who were systematically treated or topically treated with corticosteroids or immunosuppressants during the 30 days prior to the screening period;
- •2) Patients who accepted systematically chemotherapy during 30 days prior to the screening period;
- •3) Patients whose hypertrophic scars are being locally infected, or with sepsis;
- •4) Hypertrophic scar patients with potential keloid trend or keloid history;
- •5) Patients with autoimmune diseases or immune insufficiency or defects
- •Patient with uncontrolled diabetes - HbA1c (glycosylated hemoglobin A1c) ≥ 8% ，with peripheral neuropathy, peripheral arterial atresia, or other vascular diseases;
- •7) Patients with abnormal anticoagulation or coagulation function;
- •8) Patients with atrophic skin diseases, rheumatism or hemopathy ;
- •9) Patients with abnormal liver and kidney function: I. AST (Aspartate Transaminase) or ALT (Alanine Transaminase) > the upper limit of normal, and total bilirubin > the upper limit of normal; Ii. AST or ALT≥1.5 times of the upper limit of normal; Iii. Creatinine clearance rate< 60mL/ min ;
- •10) Patients with infectious diseases such as positive antibody of HBV (hepatitis B virus) , HCV (hepatitis B virus), HIV (human immunodeficiency virus) or syphilis;
- •11) The patients or their family have a history of hypersensitivity or allergies to multiple substances, or serious atopic dermatitis, or are not suitable for participate this study by investigator's judgment;
- •12) Patients who are currently or possibly suffering from malignant tumors;
- •13) Patients with definite diagnosis of mental illness with irregular medication;
- •14) Patients received any treatment that may affect wound healing, cicatrization, hemostasis or anti-coagulation, possible interactions with investigational drug within 30 days prior to randomization;
- •15) The investigators judge that patients have safety risk, or cannot complete this study or collect all blood concentration because of patient's general condition, comorbidity or medical history, or abnormal physical examination/vital signs/laboratory tests/electrocardiogram;
- •16) Patients who have received scar ablation or X-ray therapy within the past 6 months;
- •17) Patients have participated in other clinical trials of medicine or devices within 30 days prior to the screening period;
- •18) Pregnant or lactating women;
- •19) Women and men of reproductive age who are not willing to use highly effective contraception during the study period and at least 3 months after the last administration.
研究组 & 干预措施
Placebo cream
The same subject will be randomized to receive topical administration of AK3280 cream or placebo cream at S1 and S3, respectively.
干预措施: Placebo cream (Drug)
8% dose AK3280 cream
After the 4-week screening period, Eligible subjects will be administered daily 8% dose AK3280 cream b.i.d. for 12weeks.
干预措施: AK3280 Cream (Drug)
2% dose AK3280 cream
After the 4-week screening period, Eligible subjects will be administered daily 2% dose AK3280 cream b.i.d. for 12weeks.
干预措施: AK3280 Cream (Drug)
4% dose AK3280 cream
After the 4-week screening period, Eligible subjects will be administered daily 4% dose AK3280 cream b.i.d. for 12weeks.
干预措施: AK3280 Cream (Drug)
结局指标
主要结局
Number of participants with abnormal 12-lead ECG readings
时间窗: Up to 14 weeks
Number of participants with abnormal Physical examination findings
时间窗: Up to 14 weeks
Physical examination ： include height, weight, head and neck, mouth, chest, abdomen, lymph nodes, nerves and mind, limbs and other sites
Number of participants with abnormal laboratory test results
时间窗: Up to 14 weeks
Laboratory tests：include blood routine examination， blood biochemistry ，urine routine test and coagulation function
Assessment of adverse events（AE）/ serious adverse events (SAEs)
时间窗: Up to 14 weeks
Adverse Events occurring from day1 to last visit will be assessed and graded according to Common Terminology Criteria for Adverse Events version 5.0.
Number of participants with abnormal Skin Examination
时间窗: Up to 14 weeks
The skin examination should be performed under sufficient light and at room temperature , including skin lesion, inflammation, allergy, Scar hyperplasia.
Number of participants with abnormal vital signs
时间窗: Up to 14 weeks
Vital signs: include pulse, respiration, body temperature and blood pressure
次要结局
- Within 12 weeks of topical administration, the proportion of scar hyperplasia/recurrence compared in S1 and S3 segment(4 weeks， 8 weeks, 12 weeks, and unscheduled visits (up to 14 weeks))
- Within 12 weeks of topical administration, the change of VSS （Vancouver Scar Scale ） total score compared in S1 and S3 segment from baseline(4 weeks， 8 weeks, 12 weeks, and unscheduled visits (up to 14 weeks))
- Within 12 weeks of topical administration, the change of mean thickness by 3D photography compared in S1 and S3 segment from baseline(4 weeks， 8 weeks, 12 weeks, and unscheduled visits (up to 14 weeks))
- Within 12 weeks of topical administration, the change of surface area per centimeter by 3D photography compared in S1 and S3 segment from baseline(4 weeks， 8 weeks, 12 weeks, and unscheduled visits (up to 14 weeks))
- Within 12 weeks of topical administration, the change of blood flow in laser speckle imaging system compared in S1 and S3 segment from baseline(4 weeks， 8 weeks, 12 weeks, and unscheduled visits (up to 14 weeks))
- Cmax (Maximum observed concentration) of AK3280 after topical administration of AK3280 onitment.(Up to 14 weeks)
- Ctrough (trough level concentration) of AK3280 after topical administration of AK3280 onitment.(Up to 14 weeks)
- Within 12 weeks of topical administration, the change of volume per centimeter by 3D photography compared in S1 and S3 segment from baseline(4 weeks， 8 weeks, 12 weeks, and unscheduled visits (up to 14 weeks))
- Tmax (Time of peak plasma concentration) of AK3280 after topical administration of AK3280 onitment.(Up to 14 weeks)
- AUC0-t (Area under the concentration-time curve from time zero to the last measurable concentration ) of AK3280 after topical administration of AK3280 onitment.(Up to 14 weeks)
- CL/F (apparent clearance) of AK3280 after topical administration of AK3280 onitment.(Up to 14 weeks)
- Cmax of AK3280 M2 after topical administration of AK3280 onitment.(Up to 14 weeks)
- Tmax of AK3280 M2 after topical administration of AK3280 onitment.(Up to 14 weeks)
- Ctrough of AK3280 M2 after topical administration of AK3280 onitment.(Up to 14 weeks)
- AUC0-t of AK3280 M2 after topical administration of AK3280 onitment.(Up to 14 weeks)
- CL/F of AK3280 M2 after topical administration of AK3280 onitment.(Up to 14 weeks)