Thalassemia MajorPhase 2NCT03637556
Pilot Study to Assess the Safety, PK and Iron Chelating Activity of DST-0509 (Deferasirox) in Thalassemia Patients Refractory to Chelation
A Phase 2 study testing DST-0509, Jadenu and Exjade in people with Thalassemia Major, run by DisperSol Technologies, LLC at 4 sites in 2 countries.
Trial summary
This study is a multicenter, open-label, two-period crossover design that evaluates the safety, tolerability, pharmacokinetics and preliminary evidence of iron chelating activity of DST-0509 as compared to Jadenu and Exjade in transfusion-dependent thalassemia patients with transfusional iron overload, requiring iron… Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Thalassemia Major
- What is being tested?
- DST-0509, Jadenu and Exjade
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 20 Aug 2019to 16 Aug 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Written informed consent or assent as appropriate obtained prior to any study-related procedure being performed;
- Patients at least 8 years of age or older at the time of consent or assent;
- Patient with TDT syndrome and iron overload currently receiving iron chelation therapy with Jadenu or Exjade and demonstrating inadequate response assessed with serum ferritin and LIC;
- At least 8 or more blood transfusions in the past year;
- Survival expected of >12 months;
- Patient previously on dual iron chelation therapy will be transfered to iron chelation monotherapy ,stable dosing with Jadenu or Exjade for ≥1month prior to screening and receiving doses in the maximal dose range per day (e.g., Jadenu: >21 mg/kg or Exjade: >30 mg/kg, with specific doses in these ranges prescribed at the physician's discretion);
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- Serum ferritin levels that are persistently >800 mcg/L determined by 2 separate assessments during screening over the previous 2-4 weeks prior to study treatment and not showing a decreasing trend over these weeks OR, an LIC of >5 mg Fe/g dw measured by MRI in the 52 weeks prior to study entry, OR clearly identified as a poor responder in medical records within 3 months prior to the study
- Compliant with chelation therapy in the 3 months prior to enrollment in the opinion of the Investigator; has taken at least 75% of medication prescribed on a regular basis was taken (Investigator enquiry into patient prescription refill records, preferably 3 months if available, SICT scores); and
- Willing to comply with chelation therapy for the duration of the study;
- The determination of compliance is at the discretion of the investigator.
- Agree not to use other anti-chelating agents concurrently;
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1;
- Women of childbearing potential (WOCBP) must use an adequate method of birth control (double barrier, e.g. hormonal control and barrier contraception) at least 28 days prior to the first administration of the study drug, during the study and for at least 30 days after the last dose of the study drug;
- Male patients whose partners are WOCBP must use an adequate method of birth control (double barrier control) at least 28 days prior to the first administration of the study drug, during the study and for at least 30 days after the last dose of the study drug; and
- Patient is willing and able to comply with all protocol required visits and assessments.
Who cannot join
- Females of childbearing potential not on an adequate method of birth control, or who are pregnant or lactating;
- History of non-compliance with chelation therapy (determined by the investigator).
- Known history of human immunodeficiency virus (HIV)
- Active hepatitis B virus (HBV), hepatitis C virus (HCV), or other known active viral hepatitis;
- Screening blood counts as follows:
- Absolute neutrophil count < 1,000/μL
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- Platelets < 50,000/μL
- Hemoglobin < 7 g/dL (transfusion support is permitted);
- Screening chemistry values as follows:
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) > 3 × upper limit of the normal reference range (ULN)
- Total bilirubin > 5 × ULN
- Creatinine > 1.5 × ULN
- Urine protein/creatinine ratio (UPCR) > 0.5 mg/mg
- Albumin < 2.8 g/dL;
- History of congestive heart failure New York Heart Association (NYHA) class III or IV or uncontrolled hypertension at screening;
- History of other malignancy within the previous 3 years, except basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer;
- In the opinion of the Investigator, evidence of major inflammatory disease that would affect ferritin levels within 14 days prior to the start of study medication;
- Major surgery within 30 days prior to the start of study medication;
- Serious persistent infection within 14 days prior to the start of study medication;
- Serious concurrent medical condition including central nervous system (CNS) disorders;
- Requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents, or has used such treatment in the past 10 days before study entry (use of prednisone or equivalent <10 mg/day orally or use of inhaled corticosteroids or topical steroids is permitted);
- Previous history of difficulty swallowing oral medications;
- Any condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures or study medication; or
- Concomitant treatment with medications described in Section "Prohibited Medications".
- Patients who screen fail for out-of-protocol laboratory values may be re-screened at the Investigator's discretion provided that more than 30 days have passed since their previous screening. Up to three re-screenings will be permitted.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Thailand3 sites
King Chulalongkorn Memorial Hospital
Bangkok, 10330
Thalassemia Center Faculty of Medicine Siriraj Hospital
Bangkok, 10700
Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, 50200
United States1 site
Weill Cornell Medicine, New York-Presbyterian Hospital
New York, New York, 10065
About this study
Official title: A Multi-Center, Open-Label, Two-Period Cross-Over, Patient-Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Iron Chelating Activity of DST-0509 (Deferasirox) Tablets in Thalassemia Patients With Inadequate Response to Standard Chelation Therapy
This study is a multicenter, open-label, two-period crossover design that evaluates the safety, tolerability, pharmacokinetics and preliminary evidence of iron chelating activity of DST-0509 as compared to Jadenu and Exjade in transfusion-dependent thalassemia patients with transfusional iron overload, requiring iron chelation therapy and demonstrating an inadequate response to Jadenu or Exjade for greater than 3 months duration. Up to 36 patients will be evaluated (18 in each treatment arm), however, the balanced randomization may enroll fewer patients based on recruitment status.
Read the detailed description
This is a multi-center, open-label, two-period cross-over, patient-pilot study comparing DST-0509 to patient's prior ICT (Exjade or Jadenu) administered orally once daily (QD) for 28-days in each period, with a 6-day washout before the first treatment period, between treatment periods, and at the end of the study before patients recommence their prescription regimens. Patients will be randomized to one of two treatment sequences: DST 0509→Exjade/Jadenu or Exjade/Jadenu→DST-0509 (with subjects who were taking Exjade prior to study start receiving Exjade and those taking Jadenu at study start receiving Jadenu). This study is designed to assess the safety, tolerability, evidence of iron chelating activity, and PK profile of DST-0509 compared to Jadenu or Exjade in inadequately responding patients.
Up to 36 patients will be randomized 1:1 into one of two treatment sequences (study arms), of which up to 100% may be on Jadenu or Exjade at study entry, or a mix of the two. The planned randomization will assign up to 18 patients in each of two sequences: Sequence A: DST-0509 crossed to Exjade or Jadenu; Sequence B: Jadenu or Exjade crossed to DST-0509. The comparator treatment will be the patient's current chelation treatment. At the end of the study, patients previously on Jadenu or Exjade will revert to receiving their pre-study medication and dose following a 6-day washout period. A sufficient number of patients will be enrolled so there will be no need to replace study drop-outs. Study duration is approximately 14 weeks for each patient.
- Conditions
- Thalassemia Major
- Being tested
- DST-0509, Jadenu, Exjade
- Keywords
- thalassemia, iron, chelation, deferasirox, DST-0509, transfusion
- Medical subject headings
- beta-Thalassemia, Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DST-0509Drug
Also called deferasirox tablets
Novel iron chelator with improved absorption characteristics
JadenuDrug
Also called deferasirox tablets
Commercial iron chelator with standard absorption characteristics
ExjadeDrug
Also called deferasirox oral suspension
Commercial iron chelator with standard absorption characteristics
| Study group | Role | What they receive |
|---|---|---|
| DST-0509 | Experimental | DST-0509 (deferasirox) will be supplied in 360 mg, 180 mg and 90 mg tablets. DST-0509 is taken once daily with food; the first dose will be taken at Visit 3 (Day 1) and the final dose will be taken at Visit 10 (Day 63). Receives: Drug: DST-0509 |
| Jadenu | Active comparator | Jadenu is commercially available as tablets and will be provided by the patient with their ongoing prescription. Dosing will be at equivalent (mg for mg) doses of DST-0509 or Jadenu. Jadenu is taken once daily with or without a light meal. However, Jadenu can be administered according to the patient's current prescription regimen. The first dose will be taken at Visit 3 (Day 1) and the final dose will be taken at Visit 10 (Day 63). Receives: Drug: Jadenu |
| Exjade | Active comparator | Exjade is commercially available as tablets and Exjade as tablets for oral suspension and will be provided by the patient with their ongoing prescription. Dosing will be at equivalent (mg for mg) doses of DST-0509 or Jadenu. If converting from Exjade, the dose will be scaled for each treatment by 28 mg/40 mg (treatment/Exjade). Jadenu and Exjade are taken once daily, Jadenu is taken with or without a light meal, and Exjade is recommended to be taken without food. However, either Jadenu or Exjade can be administered according to the patient's current prescription regimen. The first dose will be taken at Visit 3 (Day 1) and the final dose will be taken at Visit 10 (Day 63). Receives: Drug: Exjade |
What is being measured
The primary outcome is the main question the study is designed to answer.
diarrhea %
safety tolerability
Measured: Up to Day 70
Ferritin (mcg/L)
iron chelating activity
Measured: Up to Day 63
Secondary outcomes (3)
Area Under the Curve (AUC), mg*h/L
Area Under the Plasma Curve
Measured: Days 1, 7, 28, 36, 42 and 63
Maximum concentration (Cmax), mg/L
Peak exposure, Maximum plasma concentration
Measured: Days 1, 7, 28, 36, 42 and 63
Time to maximum concentration (Tmax), h
Time to maximum plasma concentration.
Measured: Days 1, 7, 28, 36, 42 and 63
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2018
- Study start20 Aug 2019
- Primary completion8 Jun 2021
- Study completion16 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thalassemia MajorStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- open-label, two-period cross-over
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- DisperSol Technologies, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03637556
- Sponsor's protocol ID
- DST-0509-201
- Status last verified
- Jan 2022
- First submitted
- 30 Jul 2018
- Last updated
- 1 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label, Two-Period Cross-Over, Patient-Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Iron Chelating Activity of DST-0509 (Deferasirox) Tablets in Thalassemia Patients With Inadequate Response to Standard Chelation Therapy
- ClinicalTrials.gov ID
- NCT03637556
- Acronym / sponsor ID
- DST-0509-201
- Conditions
- Thalassemia Major
- Keywords
- thalassemia, iron, chelation, deferasirox, DST-0509, transfusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- DisperSol Technologies, LLCIndustry (pharma, biotech, devices)
- Study start
- 20 Aug 2019 (actual)
- Primary completion
- 8 Jun 2021 (actual)
- Study completion
- 16 Aug 2021 (actual)
- First posted
- 20 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multicenter, open-label, two-period crossover design that evaluates the safety, tolerability, pharmacokinetics and preliminary evidence of iron chelating activity of DST-0509 as compared to Jadenu and Exjade in transfusion-dependent thalassemia patients with transfusional iron overload, requiring iron chelation therapy and demonstrating an inadequate response to Jadenu or Exjade for greater than 3 months duration. Up to 36 patients will be evaluated (18 in each treatment arm), however, the balanced randomization may enroll fewer patients based on recruitment status.
Detailed description
This is a multi-center, open-label, two-period cross-over, patient-pilot study comparing DST-0509 to patient's prior ICT (Exjade or Jadenu) administered orally once daily (QD) for 28-days in each period, with a 6-day washout before the first treatment period, between treatment periods, and at the end of the study before patients recommence their prescription regimens. Patients will be randomized to one of two treatment sequences: DST 0509→Exjade/Jadenu or Exjade/Jadenu→DST-0509 (with subjects who were taking Exjade prior to study start receiving Exjade and those taking Jadenu at study start receiving Jadenu). This study is designed to assess the safety, tolerability, evidence of iron chelating activity, and PK profile of DST-0509 compared to Jadenu or Exjade in inadequately responding patients.
Up to 36 patients will be randomized 1:1 into one of two treatment sequences (study arms), of which up to 100% may be on Jadenu or Exjade at study entry, or a mix of the two. The planned randomization will assign up to 18 patients in each of two sequences: Sequence A: DST-0509 crossed to Exjade or Jadenu; Sequence B: Jadenu or Exjade crossed to DST-0509. The comparator treatment will be the patient's current chelation treatment. At the end of the study, patients previously on Jadenu or Exjade will revert to receiving their pre-study medication and dose following a 6-day washout period. A sufficient number of patients will be enrolled so there will be no need to replace study drop-outs. Study duration is approximately 14 weeks for each patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- open-label, two-period cross-over
| Arm | Type | Receives |
|---|---|---|
| DST-0509 | Experimental | Drug: DST-0509DST-0509 (deferasirox) will be supplied in 360 mg, 180 mg and 90 mg tablets. DST-0509 is taken once daily with food; the first dose will be taken at Visit 3 (Day 1) and the final dose will be taken at Visit 10 (Day 63). |
| Jadenu | Active comparator | Drug: JadenuJadenu is commercially available as tablets and will be provided by the patient with their ongoing prescription. Dosing will be at equivalent (mg for mg) doses of DST-0509 or Jadenu. Jadenu is taken once daily with or without a light meal. However, Jadenu can be administered according to the patient's current prescription regimen. The first dose will be taken at Visit 3 (Day 1) and the final dose will be taken at Visit 10 (Day 63). |
| Exjade | Active comparator | Drug: ExjadeExjade is commercially available as tablets and Exjade as tablets for oral suspension and will be provided by the patient with their ongoing prescription. Dosing will be at equivalent (mg for mg) doses of DST-0509 or Jadenu. If converting from Exjade, the dose will be scaled for each treatment by 28 mg/40 mg (treatment/Exjade). Jadenu and Exjade are taken once daily, Jadenu is taken with or without a light meal, and Exjade is recommended to be taken without food. However, either Jadenu or Exjade can be administered according to the patient's current prescription regimen. The first dose will be taken at Visit 3 (Day 1) and the final dose will be taken at Visit 10 (Day 63). |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Written informed consent or assent as appropriate obtained prior to any study-related procedure being performed;
- Patients at least 8 years of age or older at the time of consent or assent;
- Patient with TDT syndrome and iron overload currently receiving iron chelation therapy with Jadenu or Exjade and demonstrating inadequate response assessed with serum ferritin and LIC;
- At least 8 or more blood transfusions in the past year;
- Survival expected of >12 months;
Key exclusion criteria (25 listed)
- Females of childbearing potential not on an adequate method of birth control, or who are pregnant or lactating;
- History of non-compliance with chelation therapy (determined by the investigator).
- Known history of human immunodeficiency virus (HIV)
- Active hepatitis B virus (HBV), hepatitis C virus (HCV), or other known active viral hepatitis;
- Screening blood counts as follows:
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 |
|---|---|---|
| DST-0509Also: deferasirox tabletsNovel iron chelator with improved absorption characteristics | Drug | DST-0509 |
| JadenuAlso: deferasirox tabletsCommercial iron chelator with standard absorption characteristics | Drug | Jadenu |
| ExjadeAlso: deferasirox oral suspensionCommercial iron chelator with standard absorption characteristics | Drug | Exjade |
Primary outcome
diarrhea %
Time frame: Up to Day 70
safety tolerability
Ferritin (mcg/L)
Time frame: Up to Day 63
iron chelating activity
3 secondary outcomes
Area Under the Curve (AUC), mg*h/L
Time frame: Days 1, 7, 28, 36, 42 and 63
Maximum concentration (Cmax), mg/L
Time frame: Days 1, 7, 28, 36, 42 and 63
Time to maximum concentration (Tmax), h
Time frame: Days 1, 7, 28, 36, 42 and 63
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2022.
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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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DST-0509, Jadenu and Exjade in people with Thalassemia Major, run by DisperSol Technologies, LLC at 4 sites in 2 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 15 inclusion and 25 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 1 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Thailand, United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
diarrhea % (time frame: Up to Day 70). 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?
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 1 Feb 2022.