A Phase Ib Double-blind, Placebo-controlled, Randomized, Dose-escalating Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Repeated Subcutaneous Injections of MT203 in Patients With Mild to Moderate Rheumatoid Arthritis on Treatment With Methotrexate
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Significant Pulmonary Function Tests
研究概览
简要总结
The purpose of this trial is primarily to investigate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis. Furthermore, the amount of MT203 in the blood will be measured and it will be investigated how the body responds to MT203 treatment and if MT203 is effective in the treatment of rheumatoid arthritis.
详细描述
The trial medication will be administered at 2 dose levels as subcutaneous injections. Each patient will receive three injections in total. The trial duration consists of a screening period (28 - 2 days prior to the first injection) and a treatment and observation period (4 months). The trial requires approximately 20 visits at the study site.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Out-patients with active rheumatoid arthritis (RA), according to the ACR 1987 revised criteria, with low to moderate disease activity (DAS28-ESR ≥ 2.6 and ≤ 5.1)
- •Patients must be on stable doses of methotrexate (MTX) ≥ 7.5 and ≤ 25 mg/week for at least 12 weeks before the first injection, with appropriate folic acid supplementation
- •Age ≥ 18 years at Screening
- •Body weight at least 50 kg at Screening; BMI: ≥ 18.0 and ≤ 30.0 kg/m2 at Screening
- •Negative tuberculosis test at Screening
- •Heterosexually active male and female patients of childbearing potential are obliged to follow whatever contraceptive and / or breastfeeding restrictions may be required for their concomitant medication(s), including methotrexate.
- •In addition, heterosexually active male and female patients of childbearing potential are required to use effective double-method contraception (one hormonal contraceptive or intrauterine device and one other additional contraceptive method) for 1 month before the first administration of the IMP, during the course of the trial, and for 6 month after the last injection of MT
- •No special requirements are made for female patients proven to be post-menopausal (at least 2 years after last menstrual period and FSH ≥ 40IU/L), surgically sterilized or hysterectomized. Likewise no special requirements for heterosexually active male who are surgical sterilized.
- •Pregnant or lactating female patients have to be excluded.
排除标准
- •Participation in another clinical trial or previous dosing in this trial
- •Use of specified medications within certain timeframes or use of certain comedications
- •History or presence of specified diseases
- •Certain laboratory parameters outside a specified range
- •Donation of blood
- •Relevant decrease in lung function
- •Infections, frequent or chronic infections, herpes zoster
- •Females: positive pregnancy test
- •Presence of history of tuberculosis
- •History of malignancy
研究组 & 干预措施
Namilumab 150 mg
Namilumab (MT203) 150 mg (low dose), subcutaneous (SC) injection, on Days 1, 15 and 29.
干预措施: namilumab (MT203) (Drug)
Namilumab 300 mg
Namilumab (MT203) 300 mg (high dose), SC injection, on Days 1, 15 and 29.
干预措施: namilumab (MT203) (Drug)
Placebo
Namilumab-matching placebo, SC injection, on Days 1, 15 and 29.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Pulmonary Function Tests
时间窗: From Day 1 Up to Day 118
Pulmonary function was determined by forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak flow.
Number of Participants With Clinically Significant Clinical Laboratory Results
时间窗: From Day 1 Up to Day 118
Blood was collected for Haematology, Chemistry and Coagulation. Urine was collected for Urinalysis. Alert values for laboratory results include the following: Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl-transpeptidase (GGT), alkaline phosphatase (AP), total bilirubin (TBil): \> 3 times upper limit of normal (ULN). Creatinine and Glucose: \> 2 times ULN. Potassium \> 6.0 or \< 3.0 mmol/L. Haemoglobin: Male \< 8.0 ;Female \< 7.0 g/dL. Erythrocytes :Male \< 3.5 x 10\^12/L or \> 7 x 10\^12/L;Female \< 3.0 x 10\^12/L or \> 6.5 x 10\^12/L. White Blood Cells (WBC): \< 2.8 x10\^9/L or \> 16.0 x 10\^9/L. Eosinophils \> 20 % of cells in the WBC differential. Platelet Count \< 75 x 10\^9/L or 600 x 10\^9/L. No alert values were identified for Coagulation or Urinalysis.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
时间窗: From Day 1 Up to Day 118
Alert values for ECG were: Heart rate \< 35 bpm or \> 120 bpm, QTc acc. to Bazett (absolute value)\> 500 ms or QTc acc. to Bazett (increase versus Baseline (pre-treatment).
Number of Participants With Clinically Significant Vital Signs
时间窗: From Day 1 Up to Day 118
Vital signs included Systolic Blood Pressure (BP), Diastolic BP, body temperature, heart rate. Alert values were: BP systolic \> 170 mmHg or \< 85 mmHg, BP diastolic \> 105 mmHg, Difference BP systolic vs. Baseline (pre-treatment) \> 40 mmHg or Pulse rate \< 35 bpm or \> 120 beats per minute (bpm).
Number of Participants With Clinically Significant Physical Examination Findings
时间窗: From Day 1 Up to Day 118
The physical examination included body system assessments: eyes, head and neck (including thyroid), ears, nose and throat, lymph nodes, cardiovascular, lungs, mammae, abdomen (liver, spleen), genitals, limbs, central and peripheral nervous system, musculoskeletal system, skin \& nails, mucosae. The Investigator classified abnormal findings as either clinically significant or not clinically significant.
Number of Participants Reporting One or More Treatment Emergent Adverse Events
时间窗: From Day 1 Up to Day 118
An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
次要结局
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203(Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose))
- Cmax: Maximum Observed Plasma Concentration for MT203(Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose))
- AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MT203(Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose))
- AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MT203(Day 29 (Pre-dose and 2 and 6 hours post-dose))
- AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for MT203(Day 29 (Pre-dose and 2 and 6 hours post-dose))
- Change From Baseline in MT203/GM-CSF Complexes in Plasma(Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, EOT Up to Day 118)
- Number of Participants With Anti-MT203 Antibodies(From Day 1 Up to Day 118)
- Terminal Phase Elimination Half-life (T1/2) for MT203(Day 29 (Pre-dose and 2 and 6 hours post-dose))
- Ctrough: Maximum Observed Plasma Concentration Pre-Dose(Days 1, 15 and 29 Pre-dose)
- Percentage of Participants With American College of Rheumatology (ACR 20) Response(Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118)
- Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR)(Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118)
- Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma(Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, End of trial (EOT) Up to Day 118)