臨床研究等提出・公開システム

非盲検，クロスオーバー

Open Label, Crossover Assignment

インヒビター保有コホートに割り付ける治験参加者は，以下の基準も満たしていなければならない：
・現在FVIIIまたはFIXに抵抗性の高力価のインヒビター（>=5 BU/mL）を有する記録がある，または現在FVIIIまたはFIXに抵抗性の低力価のインヒビター（<5 BU/mL）を有する記録があり，観察期間への組み入れ前6ヵ月以内のFVIIIまたはFIXの回収率が60%未満である。
・凝固因子補充療法中にインヒビターが確認されたが，スクリーニング時に前項に記載したインヒビターの基準を満たさない治験参加者は，事前に治験依頼者のメディカルモニターに承認を得た上で，適格性を検討できる［例：以前に高力価インヒビター（>=5 BU/mL）が確認され，FVIII製剤またはFIX製剤の再投与ができない治験参加者］。
・出血時補充療法を受けている治験参加者は，観察期間への組み入れ前の6ヵ月間にバイパス製剤による治療を必要とする出血事象［自然出血および（または）外傷性出血］が血友病Aでは6回以上，血友病Bでは4回以上認められ，観察期間中も出血時補充療法を継続する意思を有していること。

Inclusion Criteria

* Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B with a minimum weight of 35 kg at screening.
* Participant or legally authorized representative, or participant's caregiver capable of giving signed informed consent (or minor assent, when applicable).
Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria:

* No detectable or documented history of inhibitors
* Participants on FVIII/FIX routine prophylaxis who have demonstrated at least 80% compliance with scheduled prophylaxis regimen during 6 months prior to enrollment and are willing to continue to receive routine prophylaxis treatment with FVIII/FIX replacement during the Observational Phase.
* Participants with on-demand treatment regimen with >=6 acute bleeding episodes (spontaneous or traumatic) that required coagulation factor infusion during the 6 months period prior to enrollment and willing to continue to receive on demand treatment during the Observational Phase.
Participants who are enrolled into the Inhibitor Cohort must also meet the following criteria:

* Documentation of current high titer inhibitor (>=5 BU/mL) or current low titer inhibitor (<5 BU/mL) refractory to FVIII or FIX replacement and with FVIII or FIX recovery <60% of expected within previous 6 months prior to enrolment into the Observational Phase
* Hemophilia A participants with on-demand treatment regimen with >=6 bleeding episodes or hemophilia B participants with >=4 bleeding episodes (spontaneous or traumatic) necessitating treatment with bypass factor during the 6 months prior to Enrollment into Observational Phase and willing to continue to receive on-demand treatment during the Observational Phase.
* Participants who have documented inhibitors while on factor-replacement therapy but who do not meet the quantitative inhibitor criteria described in the prior bullet at the time of Screening (eg, participant with a previously documented high-titer inhibitor (>=5 BU/mL) and whose condition precludes re-challenge with FVIII or FIX replacement) may be considered for eligibility on a case-by-case basis with prior agreement from the Pfizer Medical Monitor
* Participants who meet the bleeding criteria noted above and who are on routine prophylaxis (defined as treatment by IV injection of bypass factor to prevent bleeding) and have demonstrated at least 80% compliance with scheduled prophylaxis regimen during the 6 months prior to enrollment, may be considered for eligibility on a case-by-case basis with discussion and agreement from the Pfizer medical monitor.

・冠動脈疾患，静脈または動脈血栓症，虚血性疾患の過去または現在の治療および（または）その既往歴を有する。
・予定された治験期間中に外科的処置が予定されている。
・血友病Aまたは血友病B以外の既知の凝固障害を有する。
・腎または肝機能異常を有する。
・不安定な肝疾患または胆道疾患を現在有する。
・血液学的検査値異常を有する。
・凝固活性異常を有する。
・その他の急性または慢性の医学的あるいは精神的状態や臨床検査値異常があり，治験参加や治験薬投与により危険性が増す可能性や治験結果の解釈に影響を及ぼす可能性がある治験参加者，あるいは治験責任医師が本治験への参加を不適切と判断した治験参加者。
・現在，バイパス製剤または凝固因子製剤以外による定期的補充療法を受けている。
・免疫調節薬による定期的な併用療法を受けている。
・治験薬投与期間中の免疫寛容導入療法の実施もしくは予定，または治験薬投与期間中のFVIIIもしくはFIX製剤による定期補充療法の実施
・B7841002試験またはB7841003試験においてPF-06741086を投与されたことのある治験参加者
・本治験への組み入れの30日以内（または実施国の規制に基づく期間）または半減期の5倍以内に他の治験に参加した患者または本治験の実施中に他の治験に参加する患者
・ヒト免疫不全ウイルス（HIV）陽性の場合にCD4細胞数が200/μL以下である。
・心電図に臨床的に意味のある異常が認められ，治験参加者の安全性または治験結果の解釈に影響を及ぼす可能性がある患者
・ハムスター蛋白または治験薬のその他の成分に対する過敏症またはアレルギー反応の既往歴を持つ治験参加者
・本治験の実施に直接関わっている治験実施医療機関のスタッフおよびその親類縁者，治験責任医師から指示を受けている治験実施医療機関のスタッフ，あるいは本治験の実施に直接関わっているファイザー社員およびその親類

Exclusion Criteria

* Previous or current treatment for and/or history of coronary artery diseases, venous or arterial thrombosis or ischemic disease
* Known planned surgical procedure during the planned study period.
* Known hemostatic defect other than hemophilia A or B.
* Abnormal renal or hepatic function
* Current unstable liver or biliary disease
* Abnormal hematologic parameters
* Other acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator,
* Current routine prophylaxis with bypassing agent or non-coagulation non-factor- replacement therapy, or any previous treatment with a gene therapy product for treatment of hemophilia (participants treated with prophylaxis using bypassing agents or who had prior treatment with non-factor products may be considered on a case-by-case basis).
Regular, concomitant therapy with immunomodulatory drugs

- Ongoing or planned use of immune tolerance induction during the Observational Phase or Active Treatment Phase, or prophylaxis with FVIII or FIX replacement at any time after initiation of treatment with study intervention during the Active Treatment Phase

* Previous exposure to PF 06741086 during participation in studies B7841002 and B7841003.
* Participation in other studies involving investigational drug(s) or investigational vaccines within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry and/or during study participation.
* CD4 cell count <=200/uL if human immunodeficiency virus (HIV)-positive
* Screening ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
* Individuals with hypersensitivity or an allergic reaction to hamster protein or other components of the study intervention.
* Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are Pfizer employees, including their family members, directly involved in the conduct of the study.

12歳以上

12age old over

74歳以下

74age old under

男性

Male

実施中

progressing