A Trial to Evaluate the Safety and Tolerability of Namilumab (MT203) in Patients With Mild to Moderate Rheumatoid Arthritis (PRIORA)
2015年7月24日 更新者：Takeda
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
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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
24
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- 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 MT203.
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.
Exclusion Criteria:
- 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
- Drug abuse
- 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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Namilumab 150 mg
Namilumab (MT203) 150 mg (low dose), subcutaneous (SC) injection, on Days 1, 15 and 29.
|
administered three times, subcutaneous in the abdomen
|
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実験的：Namilumab 300 mg
Namilumab (MT203) 300 mg (high dose), SC injection, on Days 1, 15 and 29.
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administered three times, subcutaneous in the abdomen
|
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プラセボコンパレーター：Placebo
Namilumab-matching placebo, SC injection, on Days 1, 15 and 29.
|
administered three times, subcutaneous in the abdomen
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of Participants With Clinically Significant Clinical Laboratory Results
時間枠：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.
|
From Day 1 Up to Day 118
|
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Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
時間枠：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).
|
From Day 1 Up to Day 118
|
|
Number of Participants With Clinically Significant Vital Signs
時間枠：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).
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From Day 1 Up to Day 118
|
|
Number of Participants With Clinically Significant Pulmonary Function Tests
時間枠：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.
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From Day 1 Up to Day 118
|
|
Number of Participants With Clinically Significant Physical Examination Findings
時間枠：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.
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From Day 1 Up to Day 118
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Number of Participants Reporting One or More Treatment Emergent Adverse Events
時間枠：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.
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From Day 1 Up to Day 118
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203
時間枠：Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
|
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax
|
Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
|
|
Cmax: Maximum Observed Plasma Concentration for MT203
時間枠：Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
|
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
|
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
時間枠：Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
|
AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]).
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Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
|
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AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MT203
時間枠：Day 29 (Pre-dose and 2 and 6 hours post-dose)
|
AUC(0-inf) is measure of area under the curve over the dosing interval (tau) (AUC(0-tau]), where tau is the length of the dosing interval in this study).
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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
時間枠：Day 29 (Pre-dose and 2 and 6 hours post-dose)
|
Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.
|
Day 29 (Pre-dose and 2 and 6 hours post-dose)
|
|
Terminal Phase Elimination Half-life (T1/2) for MT203
時間枠：Day 29 (Pre-dose and 2 and 6 hours post-dose)
|
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
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Day 29 (Pre-dose and 2 and 6 hours post-dose)
|
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Ctrough: Maximum Observed Plasma Concentration Pre-Dose
時間枠：Days 1, 15 and 29 Pre-dose
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Days 1, 15 and 29 Pre-dose
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Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma
時間枠：Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, End of trial (EOT) Up to Day 118
|
MT203/GM-CSF complexes were analysed using a procedure that quantified GM-CSF after dissociation from the complex.
The determined concentrations corresponded to the amount of total (free and complexed) GM-CSF in the plasma sample.
A positive change from Baseline indicated improvement.
|
Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, End of trial (EOT) Up to Day 118
|
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Change From Baseline in MT203/GM-CSF Complexes in Plasma
時間枠：Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, EOT Up to Day 118
|
MT203/GM-CSF complexes were analysed using a procedure that quantified GM-CSF after dissociation from the complex.
The determined concentrations corresponded to the amount of total (free and complexed) GM-CSF in the plasma sample.
A positive change from Baseline indicated improvement.
|
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
時間枠：From Day 1 Up to Day 118
|
Serum samples were tested for the presence of anti-MT203 antibodies by a bridging Electro-chemi-luminescent assay (ECL-assay).
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From Day 1 Up to Day 118
|
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Percentage of Participants With American College of Rheumatology (ACR 20) Response
時間枠：Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118
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ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.
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Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118
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Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR)
時間枠：Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118
|
Ritchie articular index (RAI); a joint count that grades the tenderness of 26 joints on a scale of 0-3); the number of swollen joints from 44 joints (swollen44); ESR in mm/hour after 1 hour and the patient's global disease activity on a Visual Analogue Scale (VAS) of 100 mm (0=no disease activity to right end of the line 100=maximum disease activity) were used to calculate DAS44-ESR using the following formula: DAS44-ESR = 0.54*sqrt(RAI) + 0.065*(swollen44) + 0.33*ln(ESR) + 0.0072*VAS.
Lower numbers were better.
A negative change from Baseline indicated improvement.
|
Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118
|
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2011年3月1日
一次修了 (実際)
2013年8月1日
研究の完了 (実際)
2013年8月1日
試験登録日
最初に提出
2011年2月18日
QC基準を満たした最初の提出物
2011年3月16日
最初の投稿 (見積もり)
2011年3月17日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年8月20日
QC基準を満たした最後の更新が送信されました
2015年7月24日
最終確認日
2015年7月1日
詳しくは
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