ATLAS-PPX: A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03549871
• Collaborator: (none)
• Enrollment: 80
• Locations: 44
• Arm: 1
• Actual Duration (Months): 44
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Primary Objective:

To characterize the frequency of bleeding episodes while receiving fitusiran treatment, relative to the frequency of bleeding episodes while receiving factor 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 patients ≥17 years of age

• To characterize the frequency of bleeding episodes during the onset and treatment periods in patients receiving fitusiran

• To characterize the safety and tolerability of fitusiran

• Annualized weight-adjusted consumption of factor/BPA

Condition or Disease	Intervention/Treatment	Phase
Hemophilia	Drug: Fitusiran	Phase 3

Detailed Description

The estimated total time on study, inclusive of Screening, for each patient is up to 15 months for patients who enroll in the extension study except for patients in the subgroup of Cohort A, which is up to 9 months. The estimated total time on study may be up to 21 months (up to 15 months in patients in the subgroup of Cohort A) in patients who do not enroll in the extension study due to the requirement for an additional up to 6 months of follow-up for monitoring of AT levels.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: Jul 25, 2018
• Actual Primary Completion Date: Jan 20, 2022
• Actual Study Completion Date: Mar 25, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fitusiran Fitusiran sub-cutaneous injection for 7 months	Drug: Fitusiran; Pharmaceutical form: solution for injection Route of administration: subcutaneous

Outcome Measures

Primary Outcome Measures

1. Annualized bleeding rate (ABR) [13 months (6 months in factor/BPA prophylaxis period and fitusiran baseline to end of study which includes one month onset period and 6 months efficacy period)]

   Annualized Bleeding Rate (ABR) in the fitusiran efficacy period and the factor or BPA prophylaxis period

Secondary Outcome Measures

1. Annualized spontaneous bleeding rate [13 months (6 months in factor/BPA prophylaxis period and fitusiran baseline to end of study which includes one month onset period and 6 months efficacy period)]

   Annualized spontaneous bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period

2. Annualized joint bleeding rate [13 months (6 months in factor/BPA prophylaxis period and fitusiran baseline to end of study which includes one month onset period and 6 months efficacy period)]

   Annualized joint bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period

3. Quality of Life (QOL) as measured by Haem-A-QOL Questionnaire score on a scale of 0-100 with higher scores representing greater impairment [7 months]

   Change in Haem-A-QOL physical health score and total score in the fitusiran treatment period

4. ABR in the onset period [1 months]

   ABR in the fitusiran onset period

5. ABR in the treatment period [7 months]

   ABR in the fitusiran treatment period

6. Annualized weight-adjusted consumption of factor/BPA [6 months]

7. Number of patients reported with treatment emergent adverse events [Up to 19 months (including up to 6 months of Antithrombin (AT) follow-up)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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 <1% or FIX level ≤2%)

• A minimum of 2 bleeding episodes requiring BPA treatment within the last 6 months prior to Screening for patients with inhibitory antibodies to factor VIII or factor IX (Cohort A). A minimum of 1 bleeding episode requiring factor treatment within the last 12 months prior to Screening for patients without inhibitory antibodies to factor VIII or factor IX (Cohort B).

• Must meet either the definition of inhibitor or non-inhibitor patient as below:

• Inhibitor:Use of BPAs for prophylaxis and for any bleeding episodes for at least the last 6 months prior to Screening, and meet one of the following Nijmegen-modified

Bethesda assay results criteria:

• Inhibitor titer of ≥0.6 BU/mL at Screening, or

• 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 patients in Cohort A patients must 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 meet each of the following criterion:

• Nijmegen-modified Bethesda assay inhibitor titer of <0.6 BU/mL at Screening and

• No use of bypassing agents 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 bypassing agents 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

• Willing and able to comply with the study requirements and to provide written informed consent and assent

Exclusion Criteria:

• 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

• HIV positive with a CD4 count of <200 cells/μL

• 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 SC injection(s)

• Any other conditions or comorbidities that would make the patient unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 0140	Little Rock	Arkansas	United States	72202
2	Investigational Site Number 0141	Loma Linda	California	United States	92354
3	Investigational Site Number 0139	Los Angeles	California	United States	90027
4	Investigational Site Number 0111	Las Vegas	Nevada	United States	89135
5	Investigational Site Number 6101	Camperdown		Australia	2050
6	Investigational Site Number 6104	Prahran		Australia	3181
7	Investigational Site Number 1102	Montreal		Canada	H1T 2M4
8	Investigational Site Number 1103	Vancouver		Canada	V6Z 1Y6
9	Investigational Site Number 8604	Beijing		China	100045
10	Investigational Site Number 4501	Copenhagen		Denmark	2100
11	Investigational Site Number 3303	Lyon		France	69677
12	Investigational Site Number 3305	Paris		France	75015
13	Investigational Site Number 5301	Crumlin		Ireland	12
14	Investigational Site Number 9701	Ramat-Gan		Israel	52621
15	Investigational Site Number 3902	Milano		Italy	20122
16	Investigational Site Number 8108	Kashihara		Japan
17	Investigational Site Number 8103	Kitakyushu		Japan
18	Investigational Site Number 8101	Nagoya		Japan
19	Investigational Site Number 8102	Nishinomiya		Japan
20	Investigational Site Number 8104	Saitama		Japan
21	Investigational Site Number 8110	Suginami		Japan	1670035
22	Investigational Site Number 8109	Tokyo		Japan
23	Investigational Site Number 8201	Busan		Korea, Republic of	602-739
24	Investigational Site Number 8202	Daejeon		Korea, Republic of	35233
25	Investigational Site Number 8204	Seoul		Korea, Republic of	3722
26	Investigational Site Number 6004	Ampang		Malaysia	68000
27	Investigational Site Number 6002	Johor Bahru		Malaysia	80100
28	Investigational Site Number 6003	Kota Kinabalu		Malaysia	88586
29	Investigational Site Number 9002	Adana		Turkey	?01130
30	Investigational Site Number 9001	Ankara		Turkey	06100
31	Investigational Site Number 9004	Antalya		Turkey	07059
32	Investigational Site Number 9008	Gaziantep		Turkey	27100
33	Investigational Site Number 9005	Istanbul		Turkey	34093
34	Investigational Site Number 9010	İzmir		Turkey	35040
35	Investigational Site Number 9003	Izmir		Turkey	TR-35100
36	Investigational Site Number 9009	Kayseri		Turkey	38039
37	Investigational Site Number 9006	Samsun		Turkey	55200
38	Investigational site number 9013	Van		Turkey	65080
39	Investigational Site Number 8003	Kyiv		Ukraine	?01135
40	Investigational Site Number 8002	Lviv		Ukraine	79044
41	Investigational Site Number 4402	Glasgow		United Kingdom	G4 0SF
42	Investigational Site Number 4407	London		United Kingdom	E1 2ES
43	Investigational Site Number 4403	London		United Kingdom	NW3 2QG
44	Investigational Site Number 4401	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT03549871
• Other Study ID Numbers: EFC15110; 2016-004087-19; ALN-AT3SC-009; U1111-1217-3270
• First Posted: Jun 8, 2018
• Last Update Posted: May 12, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Hemophilia A

Study Results

No Results Posted as of May 12, 2022