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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05987449




Registration number
NCT05987449
Ethics application status
Date submitted
4/08/2023
Date registered
14/08/2023

Titles & IDs
Public title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Scientific title
A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Secondary ID [1] 0 0
2023-503906-35-00
Secondary ID [2] 0 0
WP44714
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NXT007

Experimental: NXT007 Dose Escalation -


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Grading Scale
Timepoint [1] 0 0
From Baseline until study completion or discontinuation (up to 7.5 years)
Primary outcome [2] 0 0
Number of Participants with at Least One Clinical Laboratory Test Abnormality for Hematology Parameters
Timepoint [2] 0 0
From Baseline until study completion or discontinuation (up to 7.5 years)
Primary outcome [3] 0 0
Number of Participants with at Least One Clinical Laboratory Test Abnormality for Blood Chemistry Parameters
Timepoint [3] 0 0
From Baseline until study completion or discontinuation (up to 7.5 years)
Primary outcome [4] 0 0
Number of Participants with at Least One Vital Sign Abnormality
Timepoint [4] 0 0
From Baseline until study completion or discontinuation (up to 7.5 years)
Primary outcome [5] 0 0
Number of Participants with at Least One Abnormality on Electrocardiogram (ECG) Recordings
Timepoint [5] 0 0
From Baseline until study completion or discontinuation (up to 7.5 years)
Secondary outcome [1] 0 0
Plasma Concentration of NXT007 at Specified Timepoints
Timepoint [1] 0 0
At prespecified timepoints from Day 1 to Day 155, and every 28 days from Day 169 until study completion (up to 7.5 years)
Secondary outcome [2] 0 0
Maximum Observed Plasma Concentration (Cmax) of NXT007 After the First Dose
Timepoint [2] 0 0
At prespecified timepoints from Day 1 to Day 15
Secondary outcome [3] 0 0
Time to Maximum Observed Plasma Concentration (tmax) of NXT007 After the First Dose
Timepoint [3] 0 0
At prespecified timepoints from Day 1 to Day 15
Secondary outcome [4] 0 0
Area Under the Plasma Concentration-Time Curve (AUC) of NXT007 After the First Dose
Timepoint [4] 0 0
At prespecified timepoints from Day 1 to Day 15
Secondary outcome [5] 0 0
Number of Participants Testing Positive for Anti-Drug Antibodies Against NXT007 at Baseline and During Treatment with Study Drug
Timepoint [5] 0 0
Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [6] 0 0
Number of Participants Testing Positive for Anti-Factor VIII Inhibitors at Baseline and During Treatment with Study Drug
Timepoint [6] 0 0
Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [7] 0 0
Model-Based Annualized Bleeding Rate for Treated Bleeds
Timepoint [7] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [8] 0 0
Mean Calculated Annualized Bleeding Rate for Treated Bleeds
Timepoint [8] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [9] 0 0
Median Calculated Annualized Bleeding Rate for Treated Bleeds
Timepoint [9] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [10] 0 0
Model-Based Annualized Bleeding Rate for All Bleeds
Timepoint [10] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [11] 0 0
Mean Calculated Annualized Bleeding Rate for All Bleeds
Timepoint [11] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [12] 0 0
Median Calculated Annualized Bleeding Rate for All Bleeds
Timepoint [12] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [13] 0 0
Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds
Timepoint [13] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [14] 0 0
Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
Timepoint [14] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [15] 0 0
Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
Timepoint [15] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [16] 0 0
Model-Based Annualized Bleeding Rate for Treated Joint Bleeds
Timepoint [16] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [17] 0 0
Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds
Timepoint [17] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Secondary outcome [18] 0 0
Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds
Timepoint [18] 0 0
From first dose of study drug until study completion or discontinuation (up to 7.5 years)

Eligibility
Key inclusion criteria
* Body weight =40 kilograms (kg) at screening
* 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 AST and ALT =3× age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis
* Adequate renal function, defined as serum creatinine =2.5× age-adapted ULN and calculated creatinine clearance =30 mL/min by Cockroft-Gault formula
* Willingness and ability to comply with schedules visits, treatment plans, laboratory tests, and other study procedures
Minimum age
12 Years
Maximum age
59 Years
Sex
Males
Can healthy volunteers participate?
No
Key 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
* Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus
* 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, females under the age of 65 years
* 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
* Previous or concomitant malignancies or leukemia
* 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.
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
16/06/2032
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
District of Columbia
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
Canada
State/province [4] 0 0
British Columbia
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Italy
State/province [6] 0 0
Lombardia
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland
Country [8] 0 0
Poland
State/province [8] 0 0
Gda?sk
Country [9] 0 0
Poland
State/province [9] 0 0
Warsaw
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid
Country [11] 0 0
Spain
State/province [11] 0 0
Malaga

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: WP44714 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. Only)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05987449