Assessing Different FVIII Dose and Frequency in Immune Tolerance Induction (ITI) with ADVATE Among Hemophilia a Boys with Inhibitor (INITIATE Study): a Multicenter Open-label Non-randomized Clinical Trial

Hemophilia A is a blood coagulation disorder caused by deficient or dysfunctional clotting factor VIII (FVIII) leading to incomplete haemostasis. Patients with severe Hemophilia A are predisposed to recurrent bleeding episodes (BEs) in joints and soft tissues that culminate in debiltating arthropathy and long-term morbidity. Prophylaxis with plasma-derived or recombinant FVIII concentrates effectively restores FVIII levels in patients with Hemophilia A, and significantly reduces the risk of bleeding. A critical concern for patients receiving FVIII replacement therapy is the development of neutralising antibodies (inhibitors) against the treatment. Inhibitors develop in up to 40% of patients with severe Hemophilia A when first exposed to FVIII treatment, typically within the first 20-30 exposure days (EDs) although a residual risk remains until after 75 EDs. Inhibitors preclude the use of FVIII replacement therapy for prevention and treatment of bleeding.
Eradication of inhibitors therefore remains an important objective for Hemophilia A patients with inhibitors. Immune tolerance induction (ITI) therapy is the only clinically proven strategy for inhibitor eradication, and at least one attempt should be offered to patients with inhibitors. However, while ITI is well-studied and has a 60- 80% success rate, treatment regimens can be expensive and burdensome to patients.
There are limited data on the use of different dose regimen of FVIII ITI in China. The INITIATE Study was designed to observe treatment strategies in patients with hemophilia A with inhibitors, with a focus on evaluating the safety and effectiveness of different dose regimens of ITI. The INITIATE Study includes multiple groups to explore factors that may affect ITI outcomes, and to explore the effects of different treatment methods on patient ITI biomarkers (genomics, transcriptomics, proteins (antibodies).

Start Date01 Mar 2025

Sponsor / Collaborator

Beijing Children's Hospital.Captital Medical University

NCT05582993

/ RecruitingPhase 3

A Phase 3, Prospective, Open-label, Uncontrolled, Multicenter Study on Efficacy and Safety of Prophylaxis With Vonicog Alfa (rVWF) in Children Diagnosed With Severe Von Willebrand Disease

The main aim of the study is to evaluate the effectiveness of prophylaxis with vonicog alfa (recombinant von Willebrand factor [rVWF]) in children. This study will enroll those participants who have been previously treated with VWF product or with a plasma-derived VWF (pdVWF) product. In this study, participants will be treated with vonicog alfa (rVWF) for 12 months.
During the study, participants will visit the study clinic 5 times after treatment initiation.

Start Date06 Nov 2024

Sponsor / Collaborator

Takeda Pharmaceutical Co., Ltd.

NCT04985682

/ CompletedPhase 4

Phase 4, Multicenter, Prospective, Interventional, Post-Marketing Study in Hemophilia A Patients in India Receiving ADVATE as On-Demand or Prophylaxis Under Standard Clinical Practice

The main aim of this study is to learn more about side effects of Advate when given as standard treatment to people with hemophilia A who have already been treated.
The study sponsor will not be involved in how participants are treated but will provide instructions on how the clinics will record what happens during the study. Participants will need to visit the study doctor 5 times in total during the study. During these visits, study data will be collected by the study doctor.

Start Date14 Jan 2022

Sponsor / Collaborator

Baxalta, Inc.

[+1]

100 Clinical Results associated with Recombinant Human Coagulation Factor VIII (Takeda)

100 Translational Medicine associated with Recombinant Human Coagulation Factor VIII (Takeda)

100 Patents (Medical) associated with Recombinant Human Coagulation Factor VIII (Takeda)

339

Literatures (Medical) associated with Recombinant Human Coagulation Factor VIII (Takeda)

01 Mar 2025·CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS

Comparative Efficacy of Recombinant FVIII and Recombinant FVII Biosimilars in Severe Hemophilia A

Article

Author: Kempaiah, Prakasha ; Ranjan, Ravi ; Saxena, Renu ; Roy, Chitrali Laha ; Kannan, Meganathan ; Mahapatra, Manoranjan ; Fareed, Jawed

Background:

Hemophilia A (HA) occurs due to the deficiency of factor VIII (FVIII). Individuals with HA generally present with elevated activated partial thromboplastin time (aPTT) and normal prothrombin time (PT). The only possible treatment for this bleeding condition is factor concentrate.

Aim:

The aim of this study is to compare the effect of recombinant factor VIII (rFVIII) and recombinant factor VII (rFVII) on prothrombin time (PT), activated partial thromboplastin time (aPTT), FVIII and FVII in severe HA.

Methodology:

A mixing study was conducted on 30 samples of severe HA patients to assess the correction of PT, aPTT, FVIII, and FVII values using biosimilars of rFVIII (NovoEight and Kogenate FS) and rFVII (NovoSeven and AryoSeven) using a fully automated coagulation analyser ‘Ceveron alpha’.

Results:

All the four drugs demonstrated a significant alteration for both PT ( P < .0001) and aPTT ( P < .0001) values. A significant, notable increase of FVIII levels were observed for FVIII biosimilars. Further investigation into the effect of rFVII biosimilars on inhibitor-positive patients revealed a significant alteration in PT ( P < .0001) and aPTT ( P < .001) values.

Conclusion:

To the best of our knowledge, this is the first study to compare the effect of all four drugs on PT, aPTT, FVIII, and FVII. Two different groups of biosimilars were found to have a high potential to alter the PT and aPTT values. The FVIII biosimilars are efficient in increasing the FVIII levels.

01 Dec 2024·Blood Research

Evaluation of FVIII pharmacokinetic profiles in Korean hemophilia A patients assessed with myPKFiT: a retrospective chart review

Article

Author: Choi, Eun Jin ; Jung, Aeran ; Hwang, Taiju ; Park, Young-Shil ; Yoo, Ki-Young ; Park, Sang Kyu

Abstract:

Purpose:

This study aimed to investigate the pharmacokinetics (PK) of factor VIII (FVIII) in Korean patients, as limited information is available on the PK of FVIII in this population.

Methods:

We collected the FVIII PK results from patients with moderate-to-severe hemophilia A using myPKFiT. PK variations were assessed according to age, blood type, inhibitor history, von Willebrand factor antigen (vWF:Ag) level, and body mass index. Additionally, the correlation between the PK profile and prophylaxis regimen was specifically analyzed for each product in severe cases.

Results:

The PK data of 48 and 81 patients treated with octocog alfa and rurioctocog alfa pegol, respectively, were obtained. The median half-lives of octocog alfa and rurioctocog alfa pegol were 9.9 (range: 6.3–15.2) h and 15.3 (range: 10.4–23.9) h, respectively. The PK profiles for each product did not differ according to age group; however, blood type-O patients had shorter half-lives and time to 1% compared to non-blood type-O patients. In regression analysis, the PK of octocog alfa showed a statistically significant difference according to age, whereas the PK of rurioctocog alfa pegol correlated with vWF:Ag. Only the frequency of rurioctocog alfa pegol use showed a statistically significant difference in relation to time to 1%, although the coefficient of determination was small.

Conclusion:

This study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential.

01 Sep 2024·HAEMOPHILIA

Recombinant FVIII replacement products for haemophilia A: An updated valuation by indirect comparison measuring area under the curve

Letter

Author: Carlsson, Katarina Steen ; Fridhammar, Adam ; Persson, Sofie ; Berntorp, Erik

In this study, we present an application of the model with the aim of providing more complete information on FVIII product comparison by AUC.The original study provided valuable insights into aid decision-making for payers and other key stakeholders, however, it was limited as head-to-head comparative data were not available for all extended half-life (EHL) products.In the nine studies included in this anal., the number of patients ranged from 7 to 27.The follow-up time after infusion of each product varied from 48 to 240 h and differed in the specific time points at which the level of FVIII in the blood was measured.In the base-case anal., Jivi had the highest estimated AUC, regardless of limitations in min. FVIII level, followed by Elocta and Adynovate.When using Advate as a comparator, all SHL products had lower AUC compared with EHL and the relative estimated totals for each product vs. Advate differed.Afstyla had the highest estimated AUC among the SHL products.

News (Medical) associated with Recombinant Human Coagulation Factor VIII (Takeda)

04 Jan 2024

·www.biospace.com

Be Biopharma Expands Leadership Team as Company Transitions to Clinical Stage Organization

Angus Smith joins as Chief Financial Officer Wing-Yen Wong, M.D., joins as interim Chief Medical Officer CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Be Biopharma, Inc. (“Be Bio”), a company pioneering the development of engineered B Cell Medicines (BCMs), today announced the appointment of Angus Smith as Chief Financial Officer (CFO) and Wing-Yen Wong, M.D., as interim Chief Medical Officer (CMO). Mr. Smith brings more than 15 years of experience in the biotechnology and life sciences industry, having held C-level positions in several public companies, including his most recent role as the CFO of Affimed N.V. and co-President of the company’s U.S. subsidiary, where he was responsible for implementing a new business plan and for raising over $400M in capital to support clinical development efforts. Mr. Smith also brings nearly a decade of investment banking experience, providing strategic and financial advice across the healthcare sector. Dr. Wong brings over 35 years of experience as a practicing clinician and professor at Children’s Hospital of Los Angeles, and leading development efforts in several companies including BioMarin, Biogen, and Baxter. Most recently Dr. Wong was Group Vice-President, Head of Global Medical Affairs and Scientific Strategy at BioMarin where she was involved in the development of the most recently approved hemophilia gene therapy. “We are thrilled to welcome Angus and Wing to Be Bio,” said Joanne Smith-Farrell, Ph.D., Chief Executive Officer. “We are rapidly transitioning from a research-based company to one focused on delivering innovative medicines to patients, with our first program in hemophilia B entering the clinic this year. These accomplished and experienced leaders will further strengthen our leadership team. Angus’s long track record of financial operating experience and fundraising will be important as we advance multiple programs to the clinic, while Wing’s expertise in drug development and as a clinical scientist is particularly important as we pioneer a new class of cellular medicines, Engineered B Cell Medicines (BCMs), to dramatically improve the lives of patients.” Angus Smith Mr. Smith brings more than 15 years of experience in the biotechnology and life sciences industry, including his most recent role as the CFO of Affimed N.V. and, prior to that, at Rockwell Medical. At Affimed, Mr. Smith led all finance, accounting, and investor relations functions, implemented a new business plan and financing strategy, and raised more than $400 million. Mr. Smith began his career in healthcare investment banking, serving most recently as a Director in the Healthcare Investment Banking Group at Cantor Fitzgerald. During his nearly decade-long investment banking tenure, Mr. Smith provided strategic and financial advice to life sciences and healthcare companies. He has worked on a substantial number of transactions across the healthcare sector with an aggregate transaction value of more than $15 billion. Mr. Smith holds a B.A. in Mathematical Economics from Colgate University. Wing-Yen Wong, M.D. Dr. Wong brings over 35 years of experience as a practicing clinician and working in the biotechnology industry with a focus in the treatment and management of patients with hemophilia, sickle cell disease (SCD) and pediatric hematology/oncology. Most recently Dr. Wong was Group Vice-President, Head of Global Medical Affairs and Scientific Strategy at BioMarin and Vice President, Global Medical, Hematology and Immunology at Biogen. Prior to Biogen, Dr. Wong was the Head of Clinical Research and Global Senior Medical Director of Hemophilia/Hematology at Baxter Healthcare Corporation where she directed medical and clinical functions, including global medical support of licensed products, clinical development and new product approvals. During her tenure at Baxter, Dr. Wong successfully directed the BLA submission and launch of multiple hemophilia products including RIXUBIS®, FEIBA®, OBIZUR and ADVATE®. Prior to her work in industry, Dr. Wong spent over 15 years as a practicing clinician and professor at Children’s Hospital Los Angeles and the Los Angeles County (LAC) and University of Southern California (USC) Medical Center. As a clinician, Dr. Wong presented and published numerous studies and papers on her research in hemophilia and hematology and has served as a reviewer for medical journals including the American Journal of Hematology, Hemophilia and the Lancet. In 2003, Dr. Wong was appointed by the Secretary of Health and Human Services as a member of the Advisory Committee on Blood Safety and Availability. Dr. Wong earned her M.D. at the USC, Keck School of Medicine and a BA at Occidental College. She served a Fellowship at the LAC and USC Medical Center in pediatric hematology-oncology and was appointed Associate Professor of Pediatrics at the University of Southern California. About Engineered B Cell Medicines – A New Class of Cellular Medicines The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application – across protein classes, patient populations and therapeutic areas. About Be Biopharma Be Biopharma (“Be Bio”) is pioneering Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with Hemophilia B and other genetic diseases, cancer, and other serious conditions. With eyes locked on the patient, our team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborate to create a bold new class of cell therapies. Be Bio was founded in October 2020 by B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. Be Bio is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Alta Partners, Longwood Fund, Bristol Myers Squibb, Takeda Ventures, Seattle Children’s Research Institute and others. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at Be.Bio and our LinkedIn page. View source version on businesswire.com: Contacts Investor Contact: ir@be.bio Source: Be Biopharma, Inc. View this news release online at:

Executive ChangeASHCell Therapy

17 Jun 2020

·www.biospace.com

BioMarin Shares Additional Promising Phase I/II Data on Hemophilia A Treatment

BioMarin HQ/courtesy of BioMarin BioMarin Pharmaceutical released new data today from its previously reported four-year update of the open-label Phase I/II study of valoctocogene roxaparvovec. BioMarin HQ/courtesy of BioMarin California-based BioMarin Pharmaceutical released new data today from its previously reported four-year update of the open-label Phase I/II study of valoctocogene roxaparvovec. The investigational gene therapy treatment is designed for patients with severe hemophilia A. The results were presented at the World Federation of Hemophilia (WFH) Virtual Summit by Professor John Pasi, M.B., Ch.B., Ph.D., from Barts and the London School of Medicine and Dentistry and Chief Investigator. In the six study participants who were previously on Factor VIII prophylaxis in the 6e13 vg/kg cohort, the data showed substantial, sustained reductions in bleeding. “With four years of data, this study represents the longest duration of clinical experience for any gene therapy in hemophilia A,” said Professor Pasi. “It is exciting to observe that all study participants remain off Factor VIII prophylaxis therapy, while also experiencing a greater than 90 percent reduction in bleeding episodes from a single administration of valoctocogene roxaparvovec. These data demonstrate the very real potential of a paradigm shift in the treatment of hemophilia A and that ongoing research into gene therapies could represent an entirely new way to approach meeting the high unmet need in patients with severe hemophilia A.” The safety pro valoctocogene roxaparvovec remains consistent with previously reported data. There were no reported delayed-onset, treatment-related events. The global Phase III study of valoctocogene roxaparvovec at the 6e13 vg/kg dose is looking into the superiority of the product compared to current standards of care. “BioMarin is committed to the bleeding disorders community with the most robust and advanced clinical development program for a potential first gene therapy in severe hemophilia A,” said Hank Fuchs, M.D., President, Global Research and Development at BioMarin. Progress has been made in the treatment realm for hemophilia A as of late. Expression Therapeutics announced at the end of May that it had received clearance from the U.S. Food and Drug Administration to proceed with its Investigational New Drug Application for the clinical testing of its novel lentiviral vector-based gene therapy, ET3. Following this news, Expression Therapeutics specified that it expects to initiate a Phase I clinical trial titled ET3-201 to look into ET3 as a potential treatment for hemophilia A in the near future. “We are very excited to get the hemophilia A clinical trial underway, the first of six gene therapy products currently under development at Expression Therapeutics,” said Mohan Rao, Ph.D., CEO of Expression Therapeutics. Takeda Pharmaceutical Company Limited also announced updates on June 15 from its AHEAD global study, examining the long-term outcomes associated with ADVATE (antihemophilic factor [recombinant], rAHF) in patients with hemophilia A. “The results of the interim analysis from the AHEAD real-world outcomes study support the long-term effectiveness of rAHF for hemophilia A patients, which was maintained in a six-year observational period and bolstered by consistent [health-related quality-of-life] scores,” said Prof. Dr. med. Johannes Oldenburg, Chairman and Director, Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn AöR, Germany, who is the researcher leading the study. “Every patient is unique, and these results support a tailored and personalized approach to optimize care for patients with bleeding disorders, delivered in partnership with their treating physician.” Hemophilia is a chronic disease that causes longer-than-normal bleeding due to absent or deficient clotting factor within the blood. In 2018, hemophilia A impacted more than 173,000 people worldwide.

Gene TherapyPhase 3Clinical ResultIND

03 Feb 2017

·www.biospace.com

These 5 Biotechs Are Battling Over the $10 Billion Hemophilia Market

February 3, 2017 By Mark Terry , BioSpace.com Breaking News Staff Just yesterday, Biogen ’s hemophilia spinoff, Bioverativ launched . Bioverativ has two drugs, Eloctate for Hemophilia A and Alprolix for Hemophilia B. They created about $850 million in sales last year. And although it’s a company that has a lot of promise, with 400 employees and $325 million in cash, it’s not without its competitors. Todd Campbell , writing for The Motley Fool, takes a look. The primary advantages of Eloctate and Alprolix over their competitors is they’re longer-acting. Campbell writes, “Eloctate and Alprolix’s improved dosing schedule has resonated with doctors and patients, and as a result, their sales have taken off since winning FDA approval in 2014.”Below are four of Bioverativ’s competitors. 1. Shire Plc Shire Plc heads the competition, leading the pack when it acquired Baxalta last year. Eloctate was battling Baxalta’s Advate, and to fight that, it launched Adyvonate in November 2015, which is a twice-weekly therapy. In the third quarter of 2016, Shire reported total hemophilia revenue of $884.1 million. 2. Bayer Bayer ’s Kovalty received approval by the U.S. Food and Drug Administration (FDA) in March 2016 for Hemophilia A. It already had Kogenate on the market. In the third quarter of 2016, Bayer reported hemophilia sales of 302 million euros. 3. CSL Behring or CSL Ltd Also in 2016, CSL’s Afstyla, which is a twice-weekly treatment for hemophilia, was approved. Also, Idelvion, for Hemophilia B, received approval last year. Campbell writes, “Although CSL hasn’t updated investors on sales through the end of 2016, its full fiscal year hemophilia sales were $1 billion through June, 2016.” 4. Novo Nordisk Known mostly for its diabetes drugs, Novo Nordisk nonetheless pulls in about 9 percent of his revenue with hemophilia drugs. It is number two globally in terms of hemophilia market share. Campbell writes, “The company hopes to find out whether or not the FDA will green light N9-GP, a long-lasting hemophilia B treatment with once-weekly dosing, soon. Also, a Phase III study of N8-GP, a long-lasting hemophilia A treatment, is under way. If successful in trials, Novo Nordisk thinks it can N8-GP’s approval next year.” Bioverativ seems to have the first-mover advantage for long-lasting treatment, but these other companies have a lot of money and significant relationships with physicians. It could be a tough row to hoe. According to Grand View Research , the U.S. the global hemophilia market in 2015 was $9.3 billion and expected to grow at a CAGR of 5.6 percent to 2024. But the markets, broken into A, B, C, and others, have their own growth rates and are segmented in different countries. Grand View says, “This segmentation has been done on the basis of the coagulation factor deficiency in a particular patient. Type A is the most commonly occurring type and has been observed to be four times more prevalent than type B. Furthermore, the pharmaceutical industry is flooded with drugs to be used in the treatment of type A, thereby limiting its growth over the forecast period. Advate and Recombinate are the popular drugs manufactured by Baxalta, which are used for prophylactic treatment of type patients across the U.S., the UK, Germany, Japan, China, and South Africa.” Despite that, Grand View expects that type B-based medications will be the fastest growers. Campbell writes, “How this market shakes out in the coming year may be as uncertain as how it shakes out in the coming five to 10 years. All these companies are knee-deep in developing next-generation solutions, and that makes it tough to guess which company will come out on top. At this point, Shire may have an edge over Bioverativ, because while Bioverativ plans to start clinical trials for a longer-lasting hemophilia A drug (BIVV 073) soon, Shire’s SHP656 is already in Phase I/II studies in that indication.”

Drug ApprovalPhase 3AcquisitionBiosimilar

100 Deals associated with Recombinant Human Coagulation Factor VIII (Takeda)

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KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hemophilia A	United States	Baxter Healthcare Corp.	25 Jul 2003
Hemophilia A	United States	Takeda Pharmaceuticals U.S.A., Inc.	25 Jul 2003

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemorrhage	Phase 3	United States	Baxalta, Inc.	01 Nov 2011
Hemorrhage	Phase 3	Japan	Baxalta, Inc.	01 Nov 2011
Hemorrhage	Phase 3	Australia	Baxalta, Inc.	01 Nov 2011
Hemorrhage	Phase 3	Austria	Baxalta, Inc.	01 Nov 2011
Hemorrhage	Phase 3	Belgium	Baxalta, Inc.	01 Nov 2011
Hemorrhage	Phase 3	Bulgaria	Baxalta, Inc.	01 Nov 2011
Hemorrhage	Phase 3	Canada	Baxalta, Inc.	01 Nov 2011
Hemorrhage	Phase 3	Germany	Baxalta, Inc.	01 Nov 2011
Hemorrhage	Phase 3	India	Baxalta, Inc.	01 Nov 2011
Hemorrhage	Phase 3	Italy	Baxalta, Inc.	01 Nov 2011

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05042440 (Phase 1 sequential pharmacokinetic study, EHA2024) Manual	Phase 1	Hemophilia A FVIII	13	Octocog alfa	gkzzvetqhf(fxptlezjrt) = saxyseavhi bnzspyzkfp (apvoyedwik ) View more	Positive	14 May 2024
	Phase 1	Hemophilia A FVIII	13	Rurioctocog alfa pegol	gkzzvetqhf(fxptlezjrt) = rhaktemjhu bnzspyzkfp (apvoyedwik ) View more	Positive	14 May 2024
NCT04985682 (CTgov)	Phase 4	Hemophilia A	50	ADVATE	elzdoiithp = qxkrddpkdo kivwgsrndd (uyvwmanzse, tmjyupvqzp - ehejlxumax) View more	-	07 Mar 2024
NCT02306694 (CTgov)	Phase 3	Hemophilia A \| Bone Diseases	16	Advate	zntzmhtyqw(pxdjmwfuyp) = knffdbuhfy olvgiwgzlf (efdhgkfuaz, 1.22) View more	-	24 Mar 2020
NCT01085344 (CHPS, CTgov)	Phase 4	Hemophilia A	56	Recombinant Factor VIII (Advate/Helixate FS/KoegenateFS)	vukddxnugb = wbaroqxdsd ldboleowmb (khqaupbqdi, pahopngome - fvyovpublp) View more	-	05 Dec 2019
ISTH2019	Not Applicable	Hemophilia A \| Fractures, Bone	-	Recombinant FVIIIC	hghirycxqq(grkfyevnfo) = qclvkqaygd ejyronthix (zderffltfx ) View more	-	10 Jun 2019
ISTH2019	Not Applicable	-	96	Octocog-alfa prophylaxis	xerdqooacq(pqyxlirnem) = ugpfowtgrh gddlvvcbgc (vjsnmuknoz ) View more	-	10 Jun 2019
EHA2017	Not Applicable	Hemophilia A	14	Octocog α	uaxoqpibcl(ycjygivqso) = bpeukgwbeq shmgksrbkt (ouxtybkdhd ) View more	-	18 May 2017
NCT00289536 (CTgov)	Phase 4	Hemophilia A	38	Antihemophilic factor, recombinant, manufactured protein-free (Low Dose)	eyijisdbhj(bcdcvbdjaj) = wepotnmupg xkiavhhmmy (hhwvormsml, piueikiomz - ecremzrsjk) View more	-	13 Jan 2011
NCT00289536 (CTgov)	Phase 4	Hemophilia A	38	Antihemophilic factor, recombinant, manufactured protein-free (Medium Dose)	eyijisdbhj(bcdcvbdjaj) = jpedkuhkpo xkiavhhmmy (hhwvormsml, xekkttajzq - ldpiakfkjp) View more	-	13 Jan 2011

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