HemophiliaPhase 3ATLAS-PPXNCT03549871
A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
A Phase 3 study testing Fitusiran, BPA prophylaxis and Factor (FVIII or FIX) prophylaxis in people with Hemophilia, run by Genzyme, a Sanofi Company at 35 sites in 15 countries.
Trial summary
Primary Objective: To characterize the frequency of bleeding episodes (BE) while receiving fitusiran treatment, relative to the frequency of bleeding episodes while receiving factor concentrate or bypassing agent (BPA) prophylaxis. Read more about this study
- Who is it for?
- Ages 12 years and older, men only
- Conditions the study is for
- Hemophilia
- What is being tested?
- Fitusiran, BPA prophylaxis and Factor (FVIII or FIX) prophylaxis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 35 sitesin 15 countries
- Study dates
- 25 Jul 2018to 25 Mar 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Males, >=12 years of age.
- Severe hemophilia A or B (as evidenced by a central laboratory measurement at screening or documented medical record evidence of FVIII less than (<) 1 percent (%) or FIX level less than or equal to (<=) 2%).
- A minimum of 2 bleeding episodes required BPA treatment within the last 6 months prior to screening for participants with inhibitory antibodies to factor VIII or factor IX (Cohort A). A minimum of 1 bleeding episode required factor treatment within the last 12 months prior to screening for participants without inhibitory antibodies to factor VIII or factor IX (Cohort B).
- Met either the definition of inhibitor or non-inhibitor participant as below:
- Inhibitor: Use of BPAs for prophylaxis and for any bleeding episodes for at least the last 6 months prior to screening, and met one of the following Nijmegen-modified Bethesda assay results criteria:
- Inhibitor titer of >=0.6 Bethesda Unit per milliliter (BU/mL) at screening, or
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- Inhibitor titer of <0.6 BU/mL at screening with medical record evidence of 2 consecutive titers >=0.6 BU/mL, or
- Inhibitor titer of <0.6 BU/mL at screening with medical record evidence of anamnestic response
- The subgroup of participants in Cohort A participants might additionally meet the following criteria to be eligible to start treatment with fitusiran directly after the screening period:
- Hemophilia B with inhibitory antibody to Factor IX as defined above
- Not responding adequately to BPA treatment (historical ABR >=20) prior to enrollment
- In the opinion of the Investigator, with approval of Sponsor Medical Monitor, 6-month BPA prophylaxis period should be omitted.
- Non-inhibitor: Use of factor concentrates for prophylaxis and for any bleeding episodes for at least the last 6 months prior to screening, and met each of the following criterion:
- Nijmegen-modified Bethesda assay inhibitor titer of <0.6 BU/mL at screening and
- No use of BPAs to treat bleeding episodes for at least the last 6 months prior to screening and
- No history of immune tolerance induction therapy within the past 3 years prior to screening.
- Documented prophylactic treatment with factor concentrates or BPAs for the treatment of hemophilia A or B for at least 6 months prior to screening.
- Adherent to the prescribed prophylactic therapy for at least 6 months prior to screening per Investigator assessment.
- Willed and complied with the study requirements and to provide written informed consent and assent.
Who cannot join
- Known co-existing bleeding disorders other than hemophilia A or B.
- AT activity <60% at screening.
- Co-existing thrombophilic disorder.
- Clinically significant liver disease.
- Active Hepatitis C virus infection.
- Acute or chronic Hepatitis B virus infection.
Show all 12Show fewer
- HIV positive with a CD4 count of <200 cells per microliter.
- History of arterial or venous thromboembolism.
- Inadequate renal function.
- History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-Acetylgalactosamine (GalNAc).
- History of intolerance to subcutaneous injection(s).
- Any other conditions or comorbidities that made the participant unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment.
Trial locations and contacts
35 sites in 15 countries.
35 sites in 15 countries
Turkey (Türkiye)10 sites
Investigational Site Number 9002
Adana, ?01130
Investigational Site Number 9001
Ankara, 06100
Investigational Site Number 9004
Antalya, 07059
Investigational Site Number 9008
Gaziantep, 27100
Investigational Site Number 9005
Istanbul, 34093
Investigational Site Number 9010
Izmir, 35040
Investigational Site Number 9003
Izmir, TR-35100
Investigational Site Number 9009
Kayseri, 38039
Investigational Site Number 9006
Samsun, 55200
Investigational site number 9013
Van, 65080
Japan4 sites
Investigational Site Number 8101
Nagoya
Investigational Site Number 8102
Nishinomiya
Investigational Site Number 8104
Saitama
Investigational Site Number 8109
Tokyo
United Kingdom4 sites
Investigational Site Number 4402
Glasgow, G4 0SF
Investigational Site Number 4407
London, E1 2ES
Investigational Site Number 4403
London, NW3 2QG
Investigational Site Number 4401
London, SE1 9RT
Malaysia3 sites
Investigational Site Number 6004
Ampang, 68000
Investigational Site Number 6002
Johor Bahru, 80100
Investigational Site Number 6003
Kota Kinabalu, 88586
South Korea3 sites
Investigational Site Number 8201
Busan, 602-739
Investigational Site Number 8202
Daejeon, 35233
Investigational Site Number 8204
Seoul, 3722
Ukraine2 sites
Investigational Site Number 8003
Kyiv, ?01135
Investigational Site Number 8002
Lviv, 79044
United States1 site
Investigational Site Number 0139
Los Angeles, California, 90027
About this study
Official title: ATLAS-PPX: an Open-label, Multinational, Switching Study to Describe the Efficacy and Safety of Fitusiran Prophylaxis in Patients With Hemophilia A and B Previously Receiving Factor or Bypassing Agent Prophylaxis.
Primary Objective:
To characterize the frequency of bleeding episodes (BE) while receiving fitusiran treatment, relative to the frequency of bleeding episodes while receiving factor concentrate or bypassing agent (BPA) prophylaxis.
Read more
Secondary Objectives:
- To characterize the following while receiving fitusiran treatment, relative to receiving factor or BPA prophylaxis:
- the frequency of spontaneous bleeding episodes
- the frequency of joint bleeding episodes
- health related quality of life (HRQOL) in participants greater than or equal to (>=) 17 years of age
- To characterize the frequency of bleeding episodes during the onset and treatment periods in participants receiving fitusiran.
- To characterize the safety and tolerability of fitusiran.
- To characterize the annualized weight-adjusted consumption of factor/BPA while receiving fitusiran treatment, relative to receiving factor or BPA prophylaxis.
Read the detailed description
The estimated total time on study, inclusive of Screening, for each participant was up to 15 months for participants who were enrolled in the extension study except for participants in the subgroup of Cohort A, for whom it was up to 9 months. The estimated total time on study was up to 21 months (up to 15 months in participants in the subgroup of Cohort A) in participants who did not enroll in the extension study due to the requirement for an additional up to 6 months of follow-up for monitoring of antithrombin (AT) levels.
- Conditions
- Hemophilia
- Being tested
- Fitusiran, BPA prophylaxis, Factor (FVIII or FIX) prophylaxis
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FitusiranDrug
Pharmaceutical form: solution for injection Route of administration: subcutaneous
BPA prophylaxisDrug
Pharmaceutical form: solution for injection Route of administration: Intravenous
Factor (FVIII or FIX) prophylaxisDrug
Pharmaceutical form: solution for injection Route of administration: Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Fitusiran | Experimental | Cohort A [inhibitor]: participants with severe hemophilia A/B and inhibitory antibodies to coagulation factor VIII (FVIII)/factor IX (FIX) previously received BPA prophylaxis. Cohort B [non-inhibitor]: participants with severe hemophilia A/B without inhibitory antibodies to FVIII/FIX previously received factor prophylaxis. Participants from both cohorts was enrolled into 6-month factor/BPA prophylaxis period and continued their pre-study, regularly scheduled prophylaxis regimen with factor/BPAs. This period could be skipped by subgroup of Cohort A (hemophilia B with inhibitors to FIX and historical annualized bleeding rate [ABR] >=20) that started directly with fitusiran. Post completing factor/BPA prophylaxis period, participants entered 7-month fitusiran treatment period (1-month onset+6-month efficacy) followed by AT follow-up/roll-over into LTE15174 (NCT03754790). Throughout study, participants could receive on-demand treatment for breakthrough BE with factor/BPAs, as appropriate. Receives: Drug: Fitusiran; Drug: BPA prophylaxis; Drug: Factor (FVIII or FIX) prophylaxis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimated Annualized Bleeding Rate (ABR)
Bleeding episodes (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/total number of days in the respective period*365.25. Estimated data were derived by using repeated measures negative binomial (NB) regression model.
Measured: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Observed Annualized Bleeding Rate (ABR)
A bleeding episode (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and counted as 1 BE towards ABR. Any bleeding that began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/number of days in the respective period *365.25.
Measured: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Secondary outcomes (13)
Estimated Annualized Spontaneous Bleeding Rate
BE: any occurrence of hemorrhage that might require administration of factor/BPA infusion. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. Spontaneous BE: BE occurrence for no apparent/known reason, particularly into joints, muscles, and soft tissues. ABR = total number of qualifying BE/number of days in respective period *365.25. Estimated data was derived using repeated measures NB regression model.
Measured: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Observed Annualized Spontaneous Bleeding Rate
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and was counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. Spontaneous BE: bleeding event occurred for no apparent or known reason, particularly into joints, muscles and soft tissues. ABR = total number of qualifying BE/number of days in respective period *365.25.
Measured: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Estimated Annualized Joint Bleeding Rate
BE: any hemorrhage that required administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection to treat BE at that location was considered part of original BE; counted as 1 BE towards ABR. Bleeding after 72 hours from last injection at that location was considered as a new event. Joint BE: characterized by unusual sensation in joint ("aura") + increasing swelling/warmth over joint skin, increasing pain/progressive loss of range of motion/difficulty in limb use compared to Baseline. ABR = total number of qualifying BE/number of days in respective period *365.25. Estimated data were derived by using repeated measures NB regression model.
Measured: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Observed Annualized Joint Bleeding Rate
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. Joint BE: characterized by unusual sensation in joint (aura) increasing swelling/warmth over joint skin, increasing pain or progressive loss of range of motion/difficulty in limb use compared to Baseline. ABR = total number of joint BE/number of days in respective period*365.25.
Measured: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Change in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Haem-A-QoL: participant-reported questionnaire for adults aged >=17 years with hemophilia and comprised of 46 items covering 10 domains. Physical health domain (PHD) is assessed with 5 items rated on 5-point Likert scale: never, rarely, sometimes, often or all the time. Raw score for PHD were transformed to scale ranged from 0 to 100, where lower scores = better physical health. Least square (LS) mean and 95% confidence interval (CI) by mixed model for repeated measure (MMRM) analysis with robust sandwich covariance matrix: change from Month -6 to Day 1 and to Month 7 as response variable; period (factor/BPA prophylaxis \& fitusiran treatment) \& Baseline score (Month -6) as fixed effects.
Measured: Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
Change in Haemophilia Quality of Life Questionnaire for Adults Total Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Haem-A-QoL: questionnaire for adults aged >= 17 years with hemophilia; and comprised of 46 items covering 10 domains: physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership and sexuality. Items were rated on 5-point Likert scale: never, rarely, sometimes, often or all time. Domain raw score was transformed to scale ranged from 0 to 100, where lower scores=better health. LS mean \& 95% CI by MMRM analysis with robust sandwich covariance matrix: change from Month -6 to Day 1 and to Month 7 as response variable; period (factor/BPA prophylaxis \& fitusiran treatment) \& Baseline score (Month -6) as fixed effects.
Measured: Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
Estimated Annualized Bleeding Rate in the Fitusiran Onset Period
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and was counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as new event. Estimated ABR and 95% CI was derived by using repeated measures NB regression model with logarithm of duration (years) that each participant spends in 1-Month fitusiran onset period matching BE data being analyzed as offset variable. ABR = total number of qualifying BE/number of days in respective period *365.25.
Measured: Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
Observed Annualized Bleeding Rate in the Fitusiran Onset Period
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and was counted as one BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. ABR= total number of qualifying BE/number of days in the 1-month onset period *365.25. Analysis was based on on-treatment strategy which included all treated bleeding events in 1-month onset period and excluded any bleeding events in period of intercurrent events.
Measured: Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
Estimated Annualized Bleeding Rate in the Fitusiran Treatment Period
BE: defined as any occurrence of hemorrhage that might require administration of factor/BPA. BE start time was time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and counted as one BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as new event. Analysis was based on on-treatment strategy which included all treated bleeding events in fitusiran period and excluded any bleeding events in the period of intercurrent events. ABR = total number of qualifying BE/number of days in respective period *365.25.
Measured: From Day 1 up to Day 190
Observed Annualized Bleeding Rate in the Fitusiran Treatment Period
BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time was time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original bleeding event and was counted as one BE towards ABR. Any bleeding that began after 72 hours from last injection at that location was considered as a new event. ABR= total number of qualifying BE/number of days in treatment period *365.25. Analysis was based on on-treatment strategy which included all treated bleeding events in fitusiran period and excluded any bleeding events in period of intercurrent events.
Measured: from Day 1 up to Day 190
Cohort A: Annualized Weight-adjusted Consumption of BPA (Activated Prothrombin Complex Concentrates)
Annualized weight-adjusted BPA consumption was calculated for each participant during prophylaxis period as: [Sum of BPA dose per body weight received during corresponding period/number of days in corresponding period]*365.25. In this outcome measure, data of annualized weight-adjusted consumption of BPA agent: aPCC (unit per kilogram [U/kg]) were reported.
Measured: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Cohort A: Annualized Weight-adjusted Consumption of BPA (Recombinant Factor VIIa)
Annualized weight-adjusted BPA consumption was calculated for each participant during prophylaxis period as: (Sum of BPA dose per body weight received during corresponding period/number of days in corresponding period)*365.25. In this outcome measure, data of annualized weight-adjusted consumption of BPA agents: rFVIIa (unit: micrograms per kg [mcg/kg]) were reported. Combined data of annualized weight-adjusted BPA consumption (mcg/kg) for both treated bleeds and prophylaxis purpose were reported in this outcome measure.
Measured: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Cohort B: Annualized Weight-adjusted Consumption of Factor
Annualized weight-adjusted BPA consumption was calculated for each participant during prophylaxis period as: (Sum of BPA dose per body weight received during corresponding period/number of days in corresponding period)*365.25. In this outcome measure, data of annualized weight-adjusted consumption of BPA agents: FVIII and FIX (unit: international Units [IU] per kg [IU/kg]) were reported.
Measured: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2018
- Study start25 Jul 2018
- Primary completion20 Jan 2022
- Study completion25 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HemophiliaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03549871
- Sponsor's protocol ID
- EFC15110
- Other IDs
- 2016-004087-19, ALN-AT3SC-009, U1111-1217-3270, 2016
- Acronym
- ATLAS-PPX
- Status last verified
- Jan 2023
- First submitted
- 25 May 2018
- Last updated
- 6 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Publications
Kenet G, Nolan B, Zulfikar B, Antmen B, Kampmann P, Matsushita T, You CW, Vilchevska K, Bagot CN, Sharif A, Peyvandi F, Young G, Negrier C, Chi J, Kittner B, Sussebach C, Shammas F, Mei B, Andersson S, Kavakli K. Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial. Blood. 2024 May 30;143(22):2256-2269. doi: 10.1182/blood.2023021864.
PubMed 38452197
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ATLAS-PPX: an Open-label, Multinational, Switching Study to Describe the Efficacy and Safety of Fitusiran Prophylaxis in Patients With Hemophilia A and B Previously Receiving Factor or Bypassing Agent Prophylaxis.
- ClinicalTrials.gov ID
- NCT03549871
- Acronym / sponsor ID
- ATLAS-PPX / EFC15110
- Conditions
- Hemophilia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 25 Jul 2018 (actual)
- Primary completion
- 20 Jan 2022 (actual)
- Study completion
- 25 Mar 2022 (actual)
- First posted
- 8 Jun 2018 (actual)
- Results
- Posted 6 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To characterize the frequency of bleeding episodes (BE) while receiving fitusiran treatment, relative to the frequency of bleeding episodes while receiving factor concentrate or bypassing agent (BPA) prophylaxis.
Secondary Objectives:
- To characterize the following while receiving fitusiran treatment, relative to receiving factor or BPA prophylaxis:
- the frequency of spontaneous bleeding episodes
- the frequency of joint bleeding episodes
- health related quality of life (HRQOL) in participants greater than or equal to (>=) 17 years of age
- To characterize the frequency of bleeding episodes during the onset and treatment periods in participants receiving fitusiran.
- To characterize the safety and tolerability of fitusiran.
- To characterize the annualized weight-adjusted consumption of factor/BPA while receiving fitusiran treatment, relative to receiving factor or BPA prophylaxis.
Detailed description
The estimated total time on study, inclusive of Screening, for each participant was up to 15 months for participants who were enrolled in the extension study except for participants in the subgroup of Cohort A, for whom it was up to 9 months. The estimated total time on study was up to 21 months (up to 15 months in participants in the subgroup of Cohort A) in participants who did not enroll in the extension study due to the requirement for an additional up to 6 months of follow-up for monitoring of antithrombin (AT) levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fitusiran | Experimental | Drug: Fitusiran, Drug: BPA prophylaxis, Drug: Factor (FVIII or FIX) prophylaxisCohort A [inhibitor]: participants with severe hemophilia A/B and inhibitory antibodies to coagulation factor VIII (FVIII)/factor IX (FIX) previously received BPA prophylaxis. Cohort B [non-inhibitor]: participants with severe hemophilia A/B without inhibitory antibodies to FVIII/FIX previously received factor prophylaxis. Participants from both cohorts was enrolled into 6-month factor/BPA prophylaxis period and continued their pre-study, regularly scheduled prophylaxis regimen with factor/BPAs. This period could be skipped by subgroup of Cohort A (hemophilia B with inhibitors to FIX and historical annualized bleeding rate [ABR] >=20) that started directly with fitusiran. Post completing factor/BPA prophylaxis period, participants entered 7-month fitusiran treatment period (1-month onset+6-month efficacy) followed by AT follow-up/roll-over into LTE15174 (NCT03754790). Throughout study, participants could receive on-demand treatment for breakthrough BE with factor/BPAs, as appropriate. |
Who may qualify
- Ages
- 12 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Males, >=12 years of age.
- Severe hemophilia A or B (as evidenced by a central laboratory measurement at screening or documented medical record evidence of FVIII less than (<) 1 percent (%) or FIX level less than or equal to (<=) 2%).
- A minimum of 2 bleeding episodes required BPA treatment within the last 6 months prior to screening for participants with inhibitory antibodies to factor VIII or factor IX (Cohort A). A minimum of 1 bleeding episode required factor treatment within the last 12 months prior to screening for participants without inhibitory antibodies to factor VIII or factor IX (Cohort B).
- Met either the definition of inhibitor or non-inhibitor participant as below:
- Inhibitor: Use of BPAs for prophylaxis and for any bleeding episodes for at least the last 6 months prior to screening, and met one of the following Nijmegen-modified Bethesda assay results criteria:
Key exclusion criteria (12 listed)
- Known co-existing bleeding disorders other than hemophilia A or B.
- AT activity <60% at screening.
- Co-existing thrombophilic disorder.
- Clinically significant liver disease.
- Active Hepatitis C virus infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FitusiranPharmaceutical form: solution for injection Route of administration: subcutaneous | Drug | Fitusiran |
| BPA prophylaxisPharmaceutical form: solution for injection Route of administration: Intravenous | Drug | Fitusiran |
| Factor (FVIII or FIX) prophylaxisPharmaceutical form: solution for injection Route of administration: Intravenous | Drug | Fitusiran |
Primary outcome
Estimated Annualized Bleeding Rate (ABR)
Time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Bleeding episodes (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/total number of days in the respective period*365.25. Estimated data were derived by using repeated measures negative binomial (NB) regression model.
Observed Annualized Bleeding Rate (ABR)
Time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
A bleeding episode (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and counted as 1 BE towards ABR. Any bleeding that began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/number of days in the respective period *365.25.
13 secondary outcomes
Estimated Annualized Spontaneous Bleeding Rate
Time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Observed Annualized Spontaneous Bleeding Rate
Time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Estimated Annualized Joint Bleeding Rate
Time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Observed Annualized Joint Bleeding Rate
Time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Change in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Time frame: Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
Change in Haemophilia Quality of Life Questionnaire for Adults Total Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Time frame: Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
Estimated Annualized Bleeding Rate in the Fitusiran Onset Period
Time frame: Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
Observed Annualized Bleeding Rate in the Fitusiran Onset Period
Time frame: Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
Estimated Annualized Bleeding Rate in the Fitusiran Treatment Period
Time frame: From Day 1 up to Day 190
Observed Annualized Bleeding Rate in the Fitusiran Treatment Period
Time frame: from Day 1 up to Day 190
Cohort A: Annualized Weight-adjusted Consumption of BPA (Activated Prothrombin Complex Concentrates)
Time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Cohort A: Annualized Weight-adjusted Consumption of BPA (Recombinant Factor VIIa)
Time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Cohort B: Annualized Weight-adjusted Consumption of Factor
Time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38452197Kenet G, Nolan B, Zulfikar B, Antmen B, Kampmann P, Matsushita T, You CW, Vilchevska K, Bagot CN, Sharif A, Peyvandi F, Young G, Negrier C, Chi J, Kittner B, Sussebach C, Shammas F, Mei B, Andersson S, Kavakli K. Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial. Blood. 2024 May 30;143(22):2256-2269. doi: 10.1182/blood.2023021864.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
35 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fitusiran, BPA prophylaxis and Factor (FVIII or FIX) prophylaxis in people with Hemophilia, run by Genzyme, a Sanofi Company at 35 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in Turkey (Türkiye), Japan, United Kingdom, Malaysia, South Korea and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Estimated Annualized Bleeding Rate (ABR) (time frame: Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03549871, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.