A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A

NCT ID: NCT05987449

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-21
• Study Completion Date: 2030-06-16

Brief Summary

WP44714 is a Phase I/II, open-label, non-randomized, global, multicenter trial consisting of two parts:

• Part 1 is a multiple-ascending dose (MAD) study in adult and adolescent male participants with severe or moderate hemophilia A with or without factor VIII (FVIII) inhibitors.
• Part 2 is a multiple-dose study in pediatric male participants with severe or moderate hemophilia A with or without FVIII inhibitors.

The overall aim of the study is to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of NXT007.

Conditions

Hemophilia A

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Cohort 1 - NXT007 Dose Level 1 (Low)

Group Type: EXPERIMENTAL

NXT007

Intervention Type: DRUG

Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.

Part 1: Cohort 2 - NXT007 Dose Level 2

Group Type: EXPERIMENTAL

NXT007

Intervention Type: DRUG

Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.

Part 1: Cohort 3 - NXT007 Dose Level 3

Group Type: EXPERIMENTAL

NXT007

Intervention Type: DRUG

Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.

Part 1: Cohort 4 - NXT007 Dose Level 4

Group Type: EXPERIMENTAL

NXT007

Intervention Type: DRUG

Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.

Part 1: Cohort 5 - NXT007 Dose Level 5 (High)

Group Type: EXPERIMENTAL

NXT007

Intervention Type: DRUG

Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.

Part 2: Cohort A - NXT007

Group Type: EXPERIMENTAL

NXT007

Intervention Type: DRUG

Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.

Interventions

NXT007

Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.

Intervention Type: DRUG

Other Intervention Names

RO7589655; RG6512

Eligibility Criteria

Inclusion Criteria

• Diagnosis of severe (Factor VIII [FVIII] coagulant activity <1 IU/dL) or moderate (FVIII coagulant activity ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A with or without inhibitors against FVIII
• Participants with FVIII inhibitors: participants using recombinant activated factor VII (rFVIIa) or willing to switch to rFVIIa as primary bypassing agent for the treatment of breakthrough bleeds, trauma, or procedures
• Historic local FVIII inhibitor test results being available during screening to confirm any previous inhibitor history and current status
• Participants who previously successfully completed immune tolerance induction (ITI) must have done so at least 5 years before screening and must have no evidence of inhibitor recurrence (permanent or temporary) since. FVIII tolerance defined as <0.6 Bethesda unit (BU)/mL (<1.0 BU/mL only for laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL) and in vivo recovery >66%
• Documentation of number and type of bleeding episodes in the last 24 weeks prior to enrollment
• Adequate hematologic function, defined as platelet count ≥100,000 cells/μL and hemoglobin ≥11 g/dL at the time of screening
• Adequate hepatic function defined as total bilirubin ≤1.5× age-adapted upper limit of normal (ULN) (excluding Gilbert syndrome) and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3× age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis. For patients with Gilbert syndrome, bilirubin should be <4 mg/dL or 68.4 umol/L at the time of screening.
• For Part 1 only: Adequate renal function, defined as serum creatinine ≤2.5× age-adapted ULN and calculated creatinine clearance ≥30 mL/min by Cockroft-Gault formula
• For Part 2 only: Adequate renal function, defined as serum creatinine ≤1.5× age-adapted ULN. When the serum creatinine is ≥1.5× ULN, creatinine clearance by Bedside Schwartz formula must be >70 mL/min/1.73m^2.
• Willingness and ability to comply with schedules visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria

• Inherited or acquired bleeding disorders other than congenital hemophilia A
• Ongoing or planned ITI therapy
• Previous or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
• At high risk for thrombotic microangiopathy (TMA), including past personal or family history of TMA, in the investigator's judgment
• For Part 1 only: Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus
• For Part 1 only: Strong family history of ischemic heart disease or cerebrovascular disease (i.e., first degree relatives such as parents, full siblings, or children): male relatives diagnosed under the age of 55 years and females under the age of 65 years
• For Part 1 only: Previous or concomitant malignancies or leukemia
• Other conditions (e.g., autoimmune conditions such as Systemic Lupus erythematosus and other systemic inflammatory disorders) that may currently increase the risk of bleeding or thrombosis
• History of clinically significant allergies
• Receipt of any of the following:

i) An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration or normalization of targeted parameters (e.g., anti-thrombin), whichever is longer; ii) A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; iii) Any other investigational drug currently being administered or planned to be administered; iv) Prior gene therapy or gene therapy planned to be administered; v) Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of anti-retroviral therapy to treat HIV.

• Protein C activity, protein S free antigen, or anti-thrombin III activity levels below the lower limit of the reference range at screening
• Known HIV infection with CD4 counts <200 cells/μL
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to excipient content
• History or presence of an abnormal ECG that is deemed clinically significant, (e.g., complete left bundle branch block, second- or third -degree atrioventricular heart block), including atrial fibrillation or evidence of prior myocardial infarction
• QT interval corrected through use of Fridericia's formula (QTcF) >450 ms demonstrated by at least two ECGs >30 minutes apart
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
• Current treatment with medications that are well known to prolong the QT interval

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

UC Davis Cancer Center

Sacramento, California, United States

Site Status: RECRUITING

Georgetown Uni Medical Center

Washington D.C., District of Columbia, United States

Site Status: WITHDRAWN

Indiana Hemophilia & Thrombosis center

Indianapolis, Indiana, United States

Site Status: RECRUITING

University of Iowa Hospitals and Clnics Dept of Pediatrics

Iowa City, Iowa, United States

Site Status: RECRUITING

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status: RECRUITING

Hamilton Health Sciences Corporation

Hamilton, Ontario, Canada

Site Status: RECRUITING

Istituto Clinico Humanitas

Rozzano (MI), Lombardy, Italy

Site Status: RECRUITING

Auckland Cancer Trial Centre

Auckland, , New Zealand

Site Status: RECRUITING

Uniwersyteckie Centrum Kliniczne

Gda?sk, , Poland

Site Status: RECRUITING

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Site Status: RECRUITING

Hospital Universitario la Paz

Madrid, , Spain

Site Status: RECRUITING

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States; Canada; Italy; New Zealand; Poland; Spain

Central Contacts

Reference Study ID Number: WP44714 https://forpatients.roche.com/

Role: CONTACT

Phone: 888-662-6728 (U.S. Only)

Email: global-roche-genentech-trials@gene.com

Other Identifiers

2023-503906-35-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

WP44714

Identifier Type: -

Identifier Source: org_study_id