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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male

Therapeutic area

Phenomena and Processes [G] - Chemical Phenomena [G02], Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

11 Oct 2023 → ongoing

Decision date (initial)

2023-09-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Others, Safety, Pharmacokinetic, Efficacy

To evaluate the safety of multiple doses of NXT007

Secondary objectives 4

1. To characterize the pharmacokinetics of NXT007 following multiple doses of NXT007
2. To evaluate the immunogenicity of multiple doses of NXT007
3. To evaluate the recurrence of or de novo factor VIII (FVIII) inhibitor occurrence, and change to FVIII inhibitor titer over time
4. To explore the efficacy of multiple doses of NXT007

Conditions and MedDRA coding

Severe or Moderate Hemophilia A with or without factor VIII inhibitors

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003550-PIP01-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male (based on sex at birth)
2. Diagnosis of severe (FVIII:C <1 IU/dL) or moderate [FVIII coagulant activity (FVIII:C) between >= 1 IU/dL and <= 5 IU/dL)] congenital hemophilia A (HA) with or without inhibitors against FVIII
3. 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
4. Historic local FVIII inhibitor test results being available during screening to confirm any previous inhibitor history and current status
5. 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 (IVR) > 66%

Exclusion criteria 6

1. Inherited or acquired bleeding disorders other than congenital HA
2. Protein C activity, protein S free antigen, or anti-thrombin III activity levels below the lower limit of the reference range at screening
3. At high risk for thrombotic microangiopathy (TMA), including past personal or family history of TMA, in the investigator’s judgment
4. 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
5. Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus (for participants =12 and <60 years)
6. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and to chimeric or humanized antibodies or fusion proteins

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1. Incidence and severity of adverse events with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 .0 (NCI CTCAE v5.0)
2. 2. Change from baseline in selected clinical laboratory test results
3. 3. Change from baseline in vital signs and electrocardiogram (ECG) parameters

Secondary endpoints 5

1. 1. Plasma concentration of NXT007 at specified timepoints and relevant pharmacokinetic (PK) parameters
2. 2. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
3. 3. Number and proportion of participants with anti-FVIII inhibitors (titer >= 0.6 BU/mL) at specified timepoints
4. 4. Number of bleeding events over time
5. 5. Annualized bleeding rate (ABR) for treated bleeds, all bleeds, treated spontaneous bleeds, and treated joint bleeds

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 6

Locations

3 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 49 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications