Trial Outcomes & Findings for Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients (NCT NCT01818726)

Last Updated: 2019-08-16

Results Overview

Change from baseline was be summarized descriptively for all on-treatment study visits. Changes to the planned statistical analysis were related to significant withdrawal of patients from the Per-Protocol Analysis Set due to a large number of patients who discontinued the study (lack of assessments of iron exchange parameters at visits) and deviations from the Protocol affecting the assessment of efficacy parameters. Because of that, the additional efficacy analysis in the Per-Protocol Analysis Set was not performed.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

15 participants

Primary outcome timeframe

Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52

Results posted on

2019-08-16

Participant Flow

Estimated number of patients was 25; the actual number of patients enrolled in the study and included in efficacy analysis was 15.

The study enrolled adult transfusion-dependent patients with Aplastic Anaemia (AA) on programmed immune suppressive treatment.

Participant milestones

Participant milestones
Measure	Serum Ferritin Level ≥ 1,000 μg/l Transfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study	Serum Ferritin Level < 1,000 μg/l Transfusion-dependent adult patients with AA and serum ferritin \< 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product
Overall Study STARTED	10	5
Overall Study COMPLETED	4	3
Overall Study NOT COMPLETED	6	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Serum Ferritin Level ≥ 1,000 μg/l Transfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study	Serum Ferritin Level < 1,000 μg/l Transfusion-dependent adult patients with AA and serum ferritin \< 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product
Overall Study Administrative reasons	5	1
Overall Study Withdrawal by Subject	0	1
Overall Study Decision to perform 2nd course of trtmnt	1	0

Baseline Characteristics

Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Serum Ferritin Level ≥ 1,000 μg/l n=10 Participants Transfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study	Serum Ferritin Level < 1,000 μg/l n=5 Participants Transfusion-dependent adult patients with AA and serum ferritin \< 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product	Total n=15 Participants Total of all reporting groups
Age, Continuous	34.0 Years STANDARD_DEVIATION 9.33 • n=93 Participants	37.0 Years STANDARD_DEVIATION 10.10 • n=4 Participants	35.0 Years STANDARD_DEVIATION 9.34 • n=27 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	4 Participants n=4 Participants	10 Participants n=27 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	1 Participants n=4 Participants	5 Participants n=27 Participants
Race/Ethnicity, Customized Caucasian	10 Participants n=93 Participants	5 Participants n=4 Participants	15 Participants n=27 Participants

PRIMARY outcome

Timeframe: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52

Population: Full Analysis Set included all patients of the Safety Analysis Set with available baseline data \& data obtained at follow-up visits \&/or final visit, for evaluation of at least 1 efficacy parameter. Statistical analysis was not performed due to large number of patients discontinuing \& thus lack of assessments of iron exchange parameters at visits.

Outcome measures

Outcome measures
Measure	Serum Ferritin Level ≥ 1,000 μg/l n=10 Participants Transfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study	Serum Ferritin Level < 1,000 μg/l n=5 Participants Transfusion-dependent adult patients with AA and serum ferritin \< 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product
Change in Serum Ferritin Values Screening	2866.14 ng/ml Standard Deviation 1460.13	769.02 ng/ml Standard Deviation 230.36
Change in Serum Ferritin Values Week 0	2895.62 ng/ml Standard Deviation 1245.81	727.68 ng/ml Standard Deviation 299.61
Change in Serum Ferritin Values Week 4	2089.62 ng/ml Standard Deviation 638.29	640.75 ng/ml Standard Deviation 292.14
Change in Serum Ferritin Values Week 8	2498.58 ng/ml Standard Deviation 1165.94	623.14 ng/ml Standard Deviation 223.27
Change in Serum Ferritin Values Week 12	2262.12 ng/ml Standard Deviation 916.65	653.62 ng/ml Standard Deviation 311.72
Change in Serum Ferritin Values Week 16	2164.01 ng/ml Standard Deviation 886.93	647.58 ng/ml Standard Deviation 225.28
Change in Serum Ferritin Values Week 20	2054.23 ng/ml Standard Deviation 729.14	646.80 ng/ml Standard Deviation 147.73
Change in Serum Ferritin Values Week 24	1710.67 ng/ml Standard Deviation 653.13	680.08 ng/ml Standard Deviation 182.24
Change in Serum Ferritin Values Week 28	1446.07 ng/ml Standard Deviation 395.17	526.17 ng/ml Standard Deviation 122.40
Change in Serum Ferritin Values Week 32	1626.28 ng/ml Standard Deviation 689.86	687.37 ng/ml Standard Deviation 114.47
Change in Serum Ferritin Values Week 36	1709.07 ng/ml Standard Deviation 1153.94	699.13 ng/ml Standard Deviation 217.38
Change in Serum Ferritin Values Week 40	1897.05 ng/ml Standard Deviation 1107.95	717.33 ng/ml Standard Deviation 306.63
Change in Serum Ferritin Values Week 44	1301.80 ng/ml Standard Deviation 460.31	661.13 ng/ml Standard Deviation 267.15
Change in Serum Ferritin Values Week 48	1740.00 ng/ml Standard Deviation 1493.24	709.50 ng/ml Standard Deviation 305.32
Change in Serum Ferritin Values Week 52	1288.80 ng/ml Standard Deviation NA N/A = not enough participants to calculate the standard deviation	655.07 ng/ml Standard Deviation 277.98

PRIMARY outcome

Timeframe: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52

Population: Full Analysis Set (FAS) included all patients of the Safety Analysis Set with the available baseline data, as well as data obtained at follow-up visits and/or the final visit, for evaluation of at least one efficacy parameter.

Mean percentage change from baseline in transferrin saturation with iron was summarized descriptively for all on-treatment study visits.

Outcome measures

PRIMARY outcome

Timeframe: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52

Mean change from baseline in serum total iron-binding capacity was summarized descriptively for all on-treatment study visits.

Outcome measures

Outcome measures
Measure	Serum Ferritin Level ≥ 1,000 μg/l n=10 Participants Transfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study	Serum Ferritin Level < 1,000 μg/l n=5 Participants Transfusion-dependent adult patients with AA and serum ferritin \< 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product
Change in Serum Total Iron-binding Capacity (TIBC) Week 32	72.85 μmol/l Standard Deviation 25.92	48.23 μmol/l Standard Deviation 2.05
Change in Serum Total Iron-binding Capacity (TIBC) Screening	4.51 μmol/l Standard Deviation 9.34	66.68 μmol/l Standard Deviation 14.95
Change in Serum Total Iron-binding Capacity (TIBC) Week 0	49.98 μmol/l Standard Deviation 10.17	49.10 μmol/l Standard Deviation 5.73
Change in Serum Total Iron-binding Capacity (TIBC) Week 4	78.70 μmol/l Standard Deviation 20.93	49.00 μmol/l Standard Deviation 4.95
Change in Serum Total Iron-binding Capacity (TIBC) Week 8	73.90 μmol/l Standard Deviation 10.97	47.44 μmol/l Standard Deviation 5.09
Change in Serum Total Iron-binding Capacity (TIBC) Week 12	83.56 μmol/l Standard Deviation 19.86	47.20 μmol/l Standard Deviation 4.68
Change in Serum Total Iron-binding Capacity (TIBC) Week 16	85.31 μmol/l Standard Deviation 23.12	49.53 μmol/l Standard Deviation 8.03
Change in Serum Total Iron-binding Capacity (TIBC) Week 20	74.34 μmol/l Standard Deviation 18.95	48.63 μmol/l Standard Deviation 4.46
Change in Serum Total Iron-binding Capacity (TIBC) Week 24	81.90 μmol/l Standard Deviation 27.17	46.53 μmol/l Standard Deviation 5.82
Change in Serum Total Iron-binding Capacity (TIBC) Week 28	101.90 μmol/l Standard Deviation 23.71	45.97 μmol/l Standard Deviation 4.14
Change in Serum Total Iron-binding Capacity (TIBC) Week 36	76.56 μmol/l Standard Deviation 19.13	47.53 μmol/l Standard Deviation 2.60
Change in Serum Total Iron-binding Capacity (TIBC) Week 40	83.50 μmol/l Standard Deviation 19.74	46.30 μmol/l Standard Deviation 4.49
Change in Serum Total Iron-binding Capacity (TIBC) Week 44	71.56 μmol/l Standard Deviation 23.95	44.10 μmol/l Standard Deviation 4.22
Change in Serum Total Iron-binding Capacity (TIBC) Week 48	74.30 μmol/l Standard Deviation 11.61	45.70 μmol/l Standard Deviation 5.57
Change in Serum Total Iron-binding Capacity (TIBC) Week 52	67.10 μmol/l Standard Deviation 26.87	46.77 μmol/l Standard Deviation 5.39

Adverse Events

Serum Ferritin Level ≥ 1,000 μg/l

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serum Ferritin Level < 1,000 μg/l

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Serum Ferritin Level ≥ 1,000 μg/l n=10 participants at risk Transfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study	Serum Ferritin Level < 1,000 μg/l n=5 participants at risk Transfusion-dependent adult patients with AA and serum ferritin \< 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product
Investigations Blood creatine increased	20.0% 2/10 • Number of events 2 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.	0.00% 0/5 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.
General disorders Weakness	10.0% 1/10 • Number of events 2 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.	0.00% 0/5 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.
Skin and subcutaneous tissue disorders Rash	10.0% 1/10 • Number of events 1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.	0.00% 0/5 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.
Gastrointestinal disorders Constipation	10.0% 1/10 • Number of events 1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.	0.00% 0/5 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.
Gastrointestinal disorders Diarrhea	10.0% 1/10 • Number of events 1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.	0.00% 0/5 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.
Gastrointestinal disorders Nausea	10.0% 1/10 • Number of events 2 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.	0.00% 0/5 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety
Publication restrictions are in place

Restriction type: OTHER

Measure	Serum Ferritin Level ≥ 1,000 μg/l n=10 Participants Transfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study	Serum Ferritin Level < 1,000 μg/l n=5 Participants Transfusion-dependent adult patients with AA and serum ferritin \< 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product
Change in Transferrin Saturation With Iron (TSI) Values Screening	88.80 Percentage of saturation Standard Deviation 10.01	53.70 Percentage of saturation Standard Deviation 10.28
Change in Transferrin Saturation With Iron (TSI) Values Week 0	87.19 Percentage of saturation Standard Deviation 10.49	54.88 Percentage of saturation Standard Deviation 14.50
Change in Transferrin Saturation With Iron (TSI) Values Week 4	73.37 Percentage of saturation Standard Deviation 8.55	50.10 Percentage of saturation Standard Deviation 14.14
Change in Transferrin Saturation With Iron (TSI) Values Week 8	72.68 Percentage of saturation Standard Deviation 9.49	49.54 Percentage of saturation Standard Deviation 17.12
Change in Transferrin Saturation With Iron (TSI) Values Week 12	72.43 Percentage of saturation Standard Deviation 5.98	49.04 Percentage of saturation Standard Deviation 10.15
Change in Transferrin Saturation With Iron (TSI) Values Week 16	68.60 Percentage of saturation Standard Deviation 9.21	52.78 Percentage of saturation Standard Deviation 9.21
Change in Transferrin Saturation With Iron (TSI) Values Week 20	68.14 Percentage of saturation Standard Deviation 19.64	50.65 Percentage of saturation Standard Deviation 11.45
Change in Transferrin Saturation With Iron (TSI) Values Week 24	74.30 Percentage of saturation Standard Deviation 11.79	5.90 Percentage of saturation Standard Deviation 5.59
Change in Transferrin Saturation With Iron (TSI) Values Week 28	65.05 Percentage of saturation Standard Deviation 7.57	52.67 Percentage of saturation Standard Deviation 12.49
Change in Transferrin Saturation With Iron (TSI) Values Week 32	75.75 Percentage of saturation Standard Deviation 12.98	49.90 Percentage of saturation Standard Deviation 11.96
Change in Transferrin Saturation With Iron (TSI) Values Week 36	65.94 Percentage of saturation Standard Deviation 13.87	47.83 Percentage of saturation Standard Deviation 4.91
Change in Transferrin Saturation With Iron (TSI) Values Week 40	66.05 Percentage of saturation Standard Deviation 9.51	43.07 Percentage of saturation Standard Deviation 2.57
Change in Transferrin Saturation With Iron (TSI) Values Week 44	69.22 Percentage of saturation Standard Deviation 16.95	33.27 Percentage of saturation Standard Deviation 9.63
Change in Transferrin Saturation With Iron (TSI) Values Week 48	71.07 Percentage of saturation Standard Deviation 12.87	44.20 Percentage of saturation Standard Deviation 1.39
Change in Transferrin Saturation With Iron (TSI) Values Week 52	83.40 Percentage of saturation Standard Deviation 11.74	43.57 Percentage of saturation Standard Deviation 4.09