Study to test the safety and how well patients with severe hemophilia A respond to treatment with BAY 2599023 (DTX 201), a drug therapy that delivers a healthy version of the defective Factor VIII gene into the nucleus of liver cells using an altered, non-infectious virus (AAV) as a "shuttle".

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bayer AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

30 Oct 2018 → ongoing

Decision date (initial)

2024-02-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Bayer AG

External identifiers

EU CT number

2023-505827-29-00

EudraCT number

2017-000806-39

ClinicalTrials.gov

NCT03588299

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response

Investigate the safety and tolerability of single ascending intravenous (IV) doses of BAY 2599023 (DTX201) in adult patients with severe hemophilia A, who have been previously treated with FVIII product

Secondary objectives 1

1. Identify a dose of BAY 2599023 (DTX201) that will achieve sustained expression of vector-derived B-domain deleted human factor VIII above 5% at 6 months and 12 months following an IV administration

Conditions and MedDRA coding

Hemophilia A

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration, Pharmaceuticals And Medical Devices Agency, Paul-Ehrlich-Institut, Ministry Of Health Labour And Welfare, Health Canada, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

No

IPD plan description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Males ≥ 18 years of age
2. Subjects with severe hemophilia A (baseline FVIII activity FVIII:C <1%) determined by measurement at the time of Screening (unless there is genetic testing compatible with severe deficiency)
3. Previously treated with FVIII concentrate(s) (plasma derived or recombinant) or cryoprecipates for a minimum of 150 exposure days (ED)
4. Are on one of the following therapies: Prophylaxis, and is willing to stop prophylactic treatment at specified time points throughout the study or On-demand: have had > 4 bleeding events in the last 52 weeks
5. Subjects must agree to use double barrier and effective contraception methods. Vasectomized subjects must agree to use condoms. This is applicable from the time of the study drug administration until notified by the investigator. Recommendation to investigators is to continue the contraception until three consecutive blood and semen samples BLOD of shed virus have been obtained. Acceptable methods of contraception include, but are not limited to, (i) condoms with a spermicidal agent (ii) diaphragm or cervical cap with spermicide; if an intra-uterine device or hormone-based contraception is used by the patient's partner, an additional barrier method must be used.
6. Male subjects must agree not to donate cells, semen, blood, tissue or organs from the time of study drug administration

Exclusion criteria 17

1. Current evidence of inhibitor to FVIII with a titer ≥ 0.6 BU/mL
2. History of inhibitor to FVIII with a titer ≥ 0.6 BU, or clinical history suggestive of inhibitor requiring modification of treatment
3. Have significant underlying liver disease as evidenced by any of the following: portal hypertension, splenomegaly, ascites, esophageal varices, hepatic encephalopathy, reduction below normal limits of serum albumin or a liver biopsy with evidence of stage 3 fibrosis
4. Any of the following: Hemoglobin <11 g/dL; Platelets <100,000 cells/μL; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × ULN; Alkaline phosphatase (AP) >2.5 × ULN; Total bilirubin >1.5 × ULN; Prothrombin time (PT) or international normalized ratio (INR) >1.0 × ULN; Serum creatinine >1.5 mg/dL
5. Have active hepatitis B or C infection, as reflected by HBsAg or HCVRNA viral load positivity
6. Currently on antiviral therapy for hepatitis B or C.
7. Serological evidence of active HIV-1 or HIV-2 as measured by CD4+ cell count <200 cells/mm3 and a viral load >50 gc/mL
8. Anti-AAVhu37 neutralizing antibody titer ≥1:5
9. Any major and/or orthopedic surgery within screening period prior to trial product administration, and at least 6 months thereafter
10. History of a malignancy for which the subject has received treatment in the past 2 years except for prostate cancer being monitored without medical intervention, or surgically removed non-melanoma skin cancer
11. Known or suspected autoimmune diseases
12. Known prior history of hypersensitivity or anaphylaxis associated with any FVIII or immunoglobulin administration.
13. Known or suspected hypersensitivity or allergic reaction to trial product(s) or related FVIII products or any component of BAY2599023 (DTX201)
14. Live vaccines within the last 30 days prior to the study drug administration; live vaccines may be re-introduced after viral shedding has been cleared
15. Subjects on treatment with immunomodulatory agents within the last 3 months prior to study entry or during the study
16. Any individual who requires any pre-medication to tolerate FVIII treatment (e.g., antihistamines)
17. Prior use of emicizumab within 3 months before dosing

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of adverse events, treatment-emergent adverse events, serious adverse events and Adverse events/serious adverse events of special interest

Secondary endpoints 2

1. Expression pattern of FVIII activity.
2. Proportion of patients in the respective dose step, that reached an expression of FVIII above 5% at 6 months and 12 months following the IV administration of BAY2599023

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bayer AG

Sponsor organisation

Bayer AG

City

Leverkusen

Postcode

51368

Country

Germany

Scientific contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Public contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Third parties 7

Locations

4 EU/EEA countries · 6 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 3 files

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

Application history

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