Study of EPN-701 for the Treatment of Calciphylaxis
Phase 2 Study of EPN-701 for the Treatment of Calciphylaxis
調査の概要
詳細な説明
This is a phase 2 double-blind RCT that will randomly assign 60 adult dialysis-dependent patients with calciphylaxis to either EPN-701 (10 mg/day administered orally) or a matched placebo in a 1:1 ratio for 24 weeks. Standardized background clinical care will be applied to all participants.
Primary objective will be to determine the clinical efficacy and safety of EPN-701 in dialysis-dependent patients with calciphylaxis. The clinical efficacy will be assessed by pre-post (Baseline-Week 24) change in pain intensity and calciphylaxis wound surface area.
Secondary objective will be to examine the safety of EPN-701 in dialysis-dependent patients with calciphylaxis. Safety will be assessed by active monitoring for adverse events throughout the trial period.
The pharmacodynamic efficacy will be primarily assessed by pre-post (Baseline-Week 12) change in plasma ucMGP among the trial arms. EPN-701 plasma concentration time profiles and other pharmacokinetic assessments will also be assessed.
Exploratory outcomes will be pre-post (Baseline-Week 24) changes in radiotracer uptake indicative of calcification burden, wound severity scores, hospitalization, mortality, and quality of life. The Investigators will also explore novel biomarkers of calciphylaxis via plasma proteomics and examine the associations between changes in ucMGP, radiotracer uptake, and novel biomarkers with patient-oriented clinical outcomes to inform the selection of efficacy endpoints for a future phase 3 RCT.
Findings from the proposed trial will inform the end point selection and design of a future phase 3 trial aimed at establishing a targeted novel therapy for calciphylaxis.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究場所
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Massachusetts
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Boston、Massachusetts、アメリカ、02114
- Renal Associates
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コンタクト:
- Scott Krinsky
- 電話番号:9784063408
- メール:skrinsky1@mgb.org
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コンタクト:
-
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Participant must provide written or electronic consent after the nature of the study has been explained, and prior to any research-related procedures, per the International Conference on Harmonization (ICH) Good Clinical Practice (GCP)
- Clinical diagnosis of calciphylaxis confirmed by the Investigator with presence of at least one ulcerated skin lesion and moderate or severe pain (worst pain intensity in the preceding 24 hours of at least 5 on a 0-10 scale). Consistent with the clinical practice and expert recommendations, histological confirmation of calciphylaxis diagnosis by a skin biopsy is not a requirement for participation.
- ESKD requiring thrice weekly hemodialysis
- Male or female aged ≥18 years
- Women of childbearing potential (WOCBP) as defined in Clinical Trials Facilitation and Coordination Group (CTFG, 2020) must have a negative serum pregnancy test (defined as serum hCG ≤25 mIU/mL [Haninger-Vacariu, 2020]) at Screening
- Women of childbearing potential (WOCBP) must be using or agree to use one highly effective form of contraception and a barrier method from Screening through 30 days after the last dose of study treatment. See Appendix C for further information about highly effective forms of contraception.
- Males who are sexually active must agree to use condoms from the period following first dose of study treatment through four weeks after the last dose of study treatment. Males with a WOCBP partner must agree to use one highly effective form of contraception in addition to condoms from Screening through 30 days after the last dose of study treatment.
- Males must agree to not donate sperm from the period following the first dose of study treatment through 4 weeks after last dose of study treatment. WOCBP who are participants or partners of fertile male participants must agree not to donate ova from the period following the first dose of study treatment through 4 weeks after last dose of study treatment.
Exclusion Criteria:
- In the opinion of the Investigator, presence of any clinically significant disease outside of calciphylaxis that may impact study participation and/or confound interpretation of the study results
- Hospitalized at the time of Screening. Patients discharged from a hospital admission ≥24 hours prior to Screening may be eligible for participation.
- Septic shock
- Hospice or comfort care including withdrawal from dialysis
- Malignancy within the last year, except non-melanoma skin cancers, cervical carcinoma in situ, or localized prostate cancer.
- Concurrent participation in another interventional clinical study and/or receipt of any other investigational new drug within four weeks prior to the first dose of study treatment, or use of an investigational device, through completion of participation in the study
- Previous participation in a study of EPN-701
- Participants who are pregnant, trying to become pregnant, or breastfeeding
- Participants who are trying to father a child
- Peritoneal dialysis participants
- Kidney transplant recipients who are receiving immunosuppression at the time of Screening and patients who have an imminent transplant plan. Patients who have received a kidney transplant that has failed, necessitating dialysis, and who are no longer on immunosuppression may participate.
- History of or current diagnosis of cirrhosis
- Current use of prohibited medications, including vitamin K-containing medications and warfarin. Patients who have discontinued warfarin treatment upon the diagnosis of calciphylaxis will be eligible for Screening.
研究計画
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:並列代入
- 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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アクティブコンパレータ:EPN-701
EPN-701 will be administered daily by mouth
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Randomized subjects will receive EPN-701 or placebo
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プラセボコンパレーター:Placebo
Placebo will be taken daily by mouth
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Randomized subjects will receive EPN-701 or placebo.
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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 |
|---|---|---|
|
Change in pain intensity (Alternate Primary Endpoint)
時間枠:Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in the worst calciphylaxis associated pain intensity as measured on the 0 to 10 scale among the trial arms.
Score of 0 indicates no pain.
Score of 10 indicates most severe pain
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Baseline-24 weeks
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Change in total calciphylaxis lesion(s) surface area (Alternate Primary Endpoint)
時間枠:Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in total surface area of ulcerated skin lesions of calciphylaxis among the trial arms
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Baseline-24 weeks
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Plasma level of uncarboxylated matrix Gla protein (uc-MGP)
時間枠:Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in plasma uncarboxylated matrix Gla protein (uc-MGP) among the trial arms
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Baseline-24 weeks
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Change in calcification burden
時間枠:Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in radiotracer uptake on 18-sodium fluoride positron emission tomography/computerized tomography (18F-NaF PET/CT)
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Baseline-24 weeks
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Changes in additional biomarkers and plasma proteomic
時間枠:Baseline-24 weeks
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Pre-post (Baseline-Week 24) changes in biomarkers such as plasma Protein induced by vitamin K absence or antagonist-II (PIVKA- II), fetuin A, and novel markers identified via plasma proteomic analyses
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Baseline-24 weeks
|
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Change in pain interference
時間枠:Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in the pain interference score recorded on Brief Pain Inventory/Short Form (BPI/SF).
Score of 0 indicates no pain interference.
Score of 10 indicates most severe pain interference.
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Baseline-24 weeks
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Change in wound Quality of Life
時間枠:Baseline-24 weeks
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Pre-post (Baseline-Week 24) score on Wound QOL.
Scores range from 0 to 4. A lower score indicates better quality of life (0=not at all impaired, 4=very much impaired.
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Baseline-24 weeks
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EPN-701 plasma concentration
時間枠:Baseline-24 weeks
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EPN-701 plasma concentration
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Baseline-24 weeks
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Rates of clinical events
時間枠:Baseline-24 weeks
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Calciphylaxis associated hospitalization, mortality, infection, or new lesion development
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Baseline-24 weeks
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 2026P000834
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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