A Clinical Trial of Study Medicine (Marstacimab) in Pediatric Patients With Hemophilia A or Hemophilia B

Hemophilia A Clinical Trial

— BASIS KIDS  

Official title:

AN OPEN-LABEL STUDY IN PEDIATRIC (<18 YEARS OF AGE), SEVERE HEMOPHILIA A PARTICIPANTS (COAGULATION FACTOR ACTIVITY <1%) WITH OR WITHOUT INHIBITORS OR MODERATELY SEVERE TO SEVERE HEMOPHILIA B PARTICIPANTS (COAGULATION FACTOR ACTIVITY =2%) WITH OR WITHOUT INHIBITORS COMPARING 12 MONTHS OF HISTORICAL STANDARD TREATMENT TO MARSTACIMAB PROPHYLAXIS

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05611801
• Other study ID #: B7841008
• Secondary ID: 2022-500495-65-0
• Status: Recruiting
• Phase: Phase 3
• Start date: December 9, 2022
• Est. completion date: September 10, 2028

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called marstacimab) for the potential treatment of hemophilia in pediatric patients.

This study will enroll pediatric participants from ages 1 to 17 years in a sequential manner. The study will open enrollment to adolescent participants aged 12 to 17 years first. Then children aged 6 to 11 years will be permitted to enroll. Lastly, children aged 1 to 5 years will be permitted to enroll.

This study will enroll participants who:

• have severe Hemophilia A or moderately severe to severe Hemophilia B (with or without inhibitors)

• have accurate historical records documenting all factor VIII, factor IX, or bypass agent infusions and hemophilia bleed events for at least 1 year prior to entering the study

• if a non-inhibitor patient, must be on a stable routine prophylaxis regimen with factor VIII or factor IX replacement products for at least 12 months prior to study entry

• if an inhibitor patient, must be on an on-demand bypass treatment regimen during the 12 months prior to study entry

All participants in this study will receive marstacimab to use prophylactically. Marstacimab will be given once a week as a subcutaneous (under the skin) shot. The first dose of marstacimab will be given at the study site by the study site staff. During the 12-month treatment period, weekly doses of marstacimab can be given at home, or if preferred, the doses may be given by the study site staff.

To help us determine if the study medicine is safe and effective, we will compare participant experiences when they are taking the study medicine to a historical period when they were not. Researchers want to see if the study medicine works to prevent the bleeding episodes commonly experienced by patients with Hemophilia.

Participants will be in this study for about 14 months (approximately 1 month in a Screening period, 12 months receiving treatment, and 1 month in a follow-up period) during which they will visit the study site at least 10 times. If preferred, and if local regulations allow it, 2 of the study visits can be completed at the participant's home instead of at the study site. There will also be 6 scheduled telephone calls approximately every 2 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 10, 2028
• Est. primary completion date: September 10, 2028
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 1 Year to 17 Years

Eligibility

Inclusion Criteria:

• Male participants of appropriate age and required minimum weight

• Participants aged 12 to 17 years must be at least 25 kgs at time of consent.

• Participants aged 6 to 11 years must be at least 19 kgs at time of consent.

• Minimum weight requirement for participants aged 1 to 5 years is to be determined.

• Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B

• Participants must have at least 1 year of diary and/or medical records available in which exogenous FVIII or FIX replacement or bypass agent infusions and hemophilic bleeding episodes were consistently documented over the 12 months prior to the time of consent.

Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria:

• No current detectable inhibitor and no documented history of inhibitors in the 5 years prior to consent

• Must have at least 50 exposure days to FVIII/FIX replacement products

• Must be at least 80% compliant with a stable and effective routine prophylaxis regimen with FVIII/FIX replacement products, for at least 12 months prior to consent

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 12 months prior to the time of consent

• Participants who have documented inhibitors while on factor-replacement therapy but who do not meet the high 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 discussion and agreement from the Pfizer medical monitor.

• Hemophilia A participants with on-demand treatment regimen with =12 bleeding episodes or hemophilia B participants with on-demand treatment regimen with =8 bleeding episodes (spontaneous or traumatic) necessitating treatment with bypass factor in the 12 months prior to informed consent

• Participants must be on an on-demand bypass treatment regimen during the 12 months prior to informed consent

Exclusion Criteria:

• Known coronary artery, thrombotic, or ischemic disease, including congenital or acquired thrombophilic disease such as Anti-thrombin III, Factor V Leiden mutation, prothrombin 20210 mutation, protein C activity, protein S activity and antiphospholipid syndrome.

• Known planned surgical procedure during the planned study period

• Known hemostatic defect other than hemophilia A or B

• Abnormal hematology, renal or hepatic function laboratory results at screening

• Other acute or chronic medical or psychiatric condition 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

• Individuals with known allergic reaction or hypersensitivity to hamster protein or other components of the study intervention

• Current routine prophylaxis with bypassing agent, non-coagulation non-factor replacement therapy (eg, emicizumab), or any previous treatment with a gene therapy product for treatment of hemophilia

• Participants with inhibitors who are being treated using a prophylaxis treatment regimen with a bypass agent, and, participants who have previously received non-factor-based hemophilia therapy (eg, fitusiran, concizumab, emicizumab) will be considered on a case-by-case basis, only after discussion and agreement between the investigator and the Pfizer medical monitor

• Regular use of immunomodulatory medications (eg, IVIG, routine systemic corticosteroids, rituximab)

• Use of systemic antifibrinolytics, medications that may increase the risk of bleeding, and certain non-steroidal anti-inflammatory drugs within 120 hours of first dose of study intervention and while on study

• Ongoing or planned use of ITI, or prophylaxis with FVIII or FIX replacement at any time after initiation of treatment with study intervention

• Participation in other studies involving investigational drug(s) or investigational vaccine(s) within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry or during study participation

• Previous exposure to marstacimab during participation in other marstacimab clinical studies

• CD4 cell count =200/uL if HIV-positive

• Abnormal ECG of clinical relevance that may affect participant safety or interpretation of study results

• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Drug:
• marstacimab
marstacimab

Locations

Country	Name	City	State
Argentina	Arbesu Hematología	Mendoza
Australia	Royal Children's Hospital	Melbourne	Victoria
Australia	Sydney Children's Hospital	Randwick	New South Wales
Austria	Medizinische Universität Wien	Vienna	Wien
Brazil	HEMOES	Vitoria	Espírito Santo
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	Hamilton Health Sciences - McMaster University Medical Centre	Hamilton	Ontario/canada
Canada	CancerCare Manitoba	Winnipeg	Manitoba
China	Beijing Children's hospital, Capital Medical University	Beijing	Beijing
China	Southern Medical University Nanfang Hospital	Guangzhou	Guangdong
China	The Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	Institute of hematology&blood disease hospital	Tianjin	Tianjin
China	Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Tongji Hospital of Tongji Medical College of HUST/Pediatric Hematology Department Pharmacy	Wuhan	Hubei
Denmark	Rigshospitalet	Copenhagen	Hovedstaden
France	Hôpital Universitaire Necker Enfants Malades	Paris
Germany	Charité Campus Virchow-Klinikum	Berlin
India	Nil Ratan Sircar Medical College and Hospital	Kolkata	WEST Bengal
India	K.J. Somaiya Hospital	Mumbai	Maharashtra
India	Nirmal Hospital Pvt Ltd.	Surat	Gujarat
Israel	Sheba Medical Center	Ramat Gan	Hamerkaz
Italy	IRCCS Istituto Giannina Gaslini	Genova	Liguria
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Ospedale Pediatrico Bambino Gesù IRCCS	Rome	Roma
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Italy	Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino	Torino
Japan	Nagano Children's Hospital	Azumino	Nagano
Japan	Nara Medical University Hospital	Kashihara	Nara
Japan	Hyogo prefectural Kobe Children's Hospital	Kobe	Hyogo
Japan	Hyogo prefectural Kobe Children's Hospital	Kobe	Hyogo
Japan	Saga University Hospital	Saga
Japan	Saitama Prefectural Children's Medical Center	Saitama-shi	Saitama
Korea, Republic of	Kyungpook National University Hospital	Daegu	Taegu-kwangyokshi
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [seoul]
Saudi Arabia	King Faisal Specialist Hospital & Research Center	An Narjis, Riyadh
Saudi Arabia	King Fahad Specialist Hospital - Dammam	Dammam	ASH Sharqiyah
Saudi Arabia	King Faisal Specialist Hospital & Research Center	Riyadh
Slovakia	Univerzitna nemocnica Bratislava, Nemocnica sv. Cyrila a Metoda	Bratislava
Slovakia	Detska fakultna nemocnica Kosice	Kosice
Slovakia	Univerzitna nemocnica Martin	Martin
South Africa	Worthwhile Clinical Trials	Benoni	Gauteng
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg	Gauteng
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	Changhua Christian Hospital	Changhua County	Changhua
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Acibadem Adana Hospital	Adana
Turkey	Gazi University Health Research and Application Center Gazi Hospital	Ankara
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi	Istanbul	I?stanbul
Turkey	Ege Universitesi Hastanesi	Izmir	I?zmir
Turkey	Erciyes Universitesi Tip Fakultesi Hastaneleri	Kayseri
Turkey	Ondokuz Mayis Universitesi	Samsun
Turkey	Erciyes University	Talas	Kayseri
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Evelina London Children's Hospital	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United States	Intermountain - Primary Children's Hospital	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  China,  Denmark,  France,  Germany,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Saudi Arabia,  Slovakia,  South Africa,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized bleeding rate (ABR) of treated bleeding events	Derived for each subject for each period (historical and study treatment) by using the following formula: ABR = number of bleeds requiring treatments/ (days on treatment period / 365.25)	Baseline to end of 12-month treatment period
Primary	Incidence of adverse events and serious adverse events		Screening through end of follow-up period (approximately 14 months)
Primary	Incidence and severity of thrombotic events		Baseline to end of 12-month treatment period
Primary	Incidence and severity of thrombotic microangiopathy		Baseline to end of 12-month treatment period
Primary	Incidence and severity of disseminated intravascular coagulation/consumption coagulopathy events		Baseline to end of 12-month treatment period
Primary	Immunogenicity (incidence of ADA and clinically significant persistent NAb against marstacimab)		Baseline to end of 12-month treatment period
Primary	Incidence and severity of injection site reaction		Baseline to end of 12-month treatment period
Primary	Incidence of severe hypersensitivity and anaphylactic reactions		Baseline to end of 12-month treatment period
Secondary	Incidence of joint bleeds (treated)		Baseline to end of 12-month treatment period
Secondary	Incidence of spontaneous bleeds (treated)		Baseline to end of 12-month treatment period
Secondary	Incidence of target joint bleeds (treated)		Baseline to end of 12-month treatment period
Secondary	Incidence of total bleeds (treated and untreated)		Baseline to end of 12-month treatment period
Secondary	Number of target joints		Baseline to end of 12-month treatment period
Secondary	Change from baseline in joint health as measured by the HJHS for participants =4 years of age		Baseline to end of 12-month treatment period
Secondary	Changes in quality of life measured by Haem-A-QoL/Haemo-QoL (using age-dependent versions for participants =8 years of age)		Baseline to end of 12-month treatment period
Secondary	Changes in quality of life measured by pedHAL (using age-dependent versions for participants =4 years of age)		Baseline to end of 12-month treatment period
Secondary	Changes in quality of life measured by Patient Global Impression of Change - Hemophilia for participants =4 years of age		Baseline to end of 12-month treatment period
Secondary	Changes in quality of life measured by Health Utilities Measure (EQ-5D-Y) for participants =4 years of age		Baseline to end of 12-month treatment period

External Links

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