Myelodysplastic Syndromes (MDS)Phase 1NCT05048498
Pharmacokinetics, Tolerability and Safety of NEX-18a
A Phase 1 study testing NEX-18a injection and Azacitidine Injection in people with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML), run by Nanexa AB at 2 sites in Sweden.
Trial summary
The study will evaluate the safety, tolerability and pharmacokinetics of NEX-18a, a long-acting injectable azacitidine, in patients diagnosed with intermediate 2 or higher-risk MDS, CMML, or AML and already on treatment with azacitidine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myeloid Leukemia (AML)
- What is being tested?
- NEX-18a injection and Azacitidine Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesSweden
- Study dates
- 27 Apr 2021to 10 Feb 2022
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written informed consent prior to any study specific procedures.
- Female and male patients ≥ 18 years of age.
- Body Mass Index (BMI) > 19 and < 30 kg/m2 BSA at screening.
- Treatment with azacitidine corresponding to 100 mg/m2 BSA x 5 per treatment cycle for at least six cycles for:
- intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System (IPSS)
- chronic myelomonocytic leukemia (CMML) with 10-29 % marrow blasts
Show all 17Show fewer
- acute myeloid leukemia (AML) according to World Health Organization (WHO) classification
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Recovery of Hematology and Clin. Chemistry assessment according to clinical praxis at the start of the last azacitidine treatment cycle before the screening visit.
- Female subject must be of non-childbearing potential (defined as pre-menopausal females with a documented tubal ligation or hysterectomy or bilateral oophorectomy; or as post-menopausal females defined as 12 months' amenorrhoea [in questionable cases a blood sample with simultaneous follicle stimulation hormone 25-140 IE/L and estradiol < 200 pmol/L is confirmatory])
- Male patients must agree to use an adequate method of contraception. Male patients who are sexually active must use, with their partner, a condom AND one of the following methods of highly effective contraception from the time of IMP administration until 90 days after the last dose of IMP.
- oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable or implanted hormonal contraceptives
- intrauterine device
- intrauterine system (for example progestin-releasing coil)
- vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)
- bilateral tubal occlusion or hysterectomy
- Willingness and ability to comply with study procedures, visit schedules, study restrictions, and requirements.
Who cannot join
- The patient has participated in any other investigational/interventional trial including an investigational drug within 30 days (or five half-lives of the study drug prior to screening, whichever is longer) prior to screening.
- Diagnosis of malignant disease within the previous 5 years (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma of the cervix or breast, or other local malignancy excised or irradiated with a high probability of cure).
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
- The patient has a history of alcohol abuse or drug abuse within the past 12 months.
- Any condition including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study.
- Lack of suitability for participation in the study, for any reason, judged by the Investigator.
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Karolinska University Hospital Huddinge
Huddinge
Kliniska Forsknings och Utvecklings Enheten KFUE
Uppsala
About this study
Official title: An Open Pilot Study to Assess the Pharmacokinetics, Tolerability, and Safety of NEX-18a Given as a Subcutaneous Injection for the Treatment of Intermediate 2 or Higher-risk MDS, CMML or AML
The study will evaluate the safety, tolerability and pharmacokinetics of NEX-18a, a long-acting injectable azacitidine, in patients diagnosed with intermediate 2 or higher-risk MDS, CMML, or AML and already on treatment with azacitidine.
Read the detailed description
Since 2010, subcutaneous treatment with azacitidine has been the first-line treatment for patients with high-risk MDS. Azacitidine has been established as a standard of care and is described in the National Comprehensive Cancer Network (NCCN) guidelines as a core component of optimal treatment of MDS. However, mainly due to its short half-life (41 minutes) when administered subcutaneously azacitidine should, according to the approved label, be administered for seven consecutive days at a dose of 75 mg/m2 body surface area (BSA) each 28-day cycle. In the Nordic Guidelines, two alternative dosing schedules may also be considered: 100 mg/m2 BSA sc day 1-5 or 75 mg/m2 BSA sc day 1-5 + 8-9 (to avoid injection during weekends).
Nanexa AB has developed NEX-18a, a subcutaneous injection of azacitidine with extended-release based on the drug delivery system, PharmaShell®. Drug particles are enclosed in a coating with controlled solubility, and as the coating dissolves over time the drug is released in a predefined manner. This technique provides a way to create drugs with a prolonged release for parenteral administration. The technology used by Nanexa to manufacture the coating is via Atomic Layer Deposition (ALD). In ALD, reactive gases are used which build up a surface coating with high precision, atomic layer by atomic layer.
NEX-18a will offer a benefit to current azacitidine treatment with a reduction of subcutaneous administrations, decreased need for pre-medication, and will reduce the time each patient has to spend in the hospital in order to receive the treatment in each cycle. In addition, the patients will spend less time traveling to and from the hospital and from a health care perspective, one injection instead of seven per cycle will reduce the time and the resources the health care provider dedicates to treating the patients.
- Conditions
- Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myeloid Leukemia (AML)
- Being tested
- NEX-18a injection, Azacitidine Injection
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NEX-18a injectionDrug
Also called PharmaShell, Azacitidine, 5-azacitidine
In Treatment phase 1, NEX-18a will be given as a single subcutaneous injection.
In Treatment phase 2, NEX-18a will be given as a single subcutaneous injection.
Azacitidine InjectionDrug
Also called Azacitidine, 5-azacitidine, Vidaza
In Treatment phase 1, azacitidine will be administered once daily for four days. In Treatment phase 2, azacitidine will be administered once daily for three days.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine | Active comparator | Treatment phase 1: the patients will receive regular treatment with azacitidine for 4 days.
Treatment phase 2: the patients will receive regular treatment with azacitidine for 3 days. Receives: Drug: Azacitidine Injection |
| NEX-18a | Experimental | Treatment phase 1: the azacitidine dose for day 5 will be replaced by a single dose NEX-18a
Treatment phase 2: the azacitidine dose for day 4 and 5 will be replaced by a single dose NEX-18a Receives: Drug: NEX-18a injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematology and Clinical Chemistry analyses
Change from baseline to 30 days follow-up. Descriptive individual data.
Measured: 0-30 days
Adverse events
Change from baseline to 30 days follow-up. Descriptive individual data.
Measured: 0-30 days
Vital signs
Change from baseline to 30 days follow-up. Descriptive individual data.
Measured: 0-30 days
Physical examination
Change from baseline to 30 days follow-up. Descriptive individual data.
Measured: 0-30 days
Local tolerance (injection site)
Change from baseline to 30 days follow-up. Descriptive individual data.
Measured: 0-30 days
Concomitant medications/therapy
Change from baseline to 30 days follow-up. Descriptive individual data.
Measured: 0-30 days
Secondary outcomes (9)
AUC-time curve
From time 0 to 24 hours
Measured: 0-24 h
AUC from time 0-last
From time 0 to last
Measured: 0-336 h
AUC from time 0 to infinity
From time 0 to infinity
Measured: 0-336 h
Plasma Concentration
Maximum Plasma Concentration
Measured: 0-336 h
Plasma Concentration over time
Plasma Concentration at 336h
Measured: 0-336 h
Half-life measurement
Terminal elimination half-life
Measured: 0-336 h
Measurement of distribution
Volume of distribution
Measured: 0-336 h
Elimination
Clearance
Measured: 0-336 h
Local tolerance of NEX-18a
Change from baseline to 30 days follow-up. Descriptive individual data. The local tolerance will be measured by inspection of injection sites. Pain, tenderness erythema/redness, and induration/swelling will be assessed by a four-grade scale where 1 is mild and 4 is potentially life threatening.
Measured: 0-30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2021
- Study start27 Apr 2021
- Primary completion10 Feb 2022
- Study completion10 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic Syndromes (MDS)Studies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nanexa AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Uppsala University
- Responsible party
- Sponsor
- Investigators
- Ulla Olsson Strömberg, MD, Principal investigator, Uppsala University, Uppsala, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05048498
- Sponsor's protocol ID
- NEX-18-01
- Status last verified
- Oct 2023
- First submitted
- 11 May 2021
- Last updated
- 17 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Pilot Study to Assess the Pharmacokinetics, Tolerability, and Safety of NEX-18a Given as a Subcutaneous Injection for the Treatment of Intermediate 2 or Higher-risk MDS, CMML or AML
- ClinicalTrials.gov ID
- NCT05048498
- Acronym / sponsor ID
- NEX-18-01
- Conditions
- Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myeloid Leukemia (AML)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Nanexa ABIndustry (pharma, biotech, devices)
- Collaborators
- Uppsala University
- Study start
- 27 Apr 2021 (actual)
- Primary completion
- 10 Feb 2022 (actual)
- Study completion
- 10 Feb 2022 (actual)
- First posted
- 17 Sep 2021 (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.
The study will evaluate the safety, tolerability and pharmacokinetics of NEX-18a, a long-acting injectable azacitidine, in patients diagnosed with intermediate 2 or higher-risk MDS, CMML, or AML and already on treatment with azacitidine.
Detailed description
Since 2010, subcutaneous treatment with azacitidine has been the first-line treatment for patients with high-risk MDS. Azacitidine has been established as a standard of care and is described in the National Comprehensive Cancer Network (NCCN) guidelines as a core component of optimal treatment of MDS. However, mainly due to its short half-life (41 minutes) when administered subcutaneously azacitidine should, according to the approved label, be administered for seven consecutive days at a dose of 75 mg/m2 body surface area (BSA) each 28-day cycle. In the Nordic Guidelines, two alternative dosing schedules may also be considered: 100 mg/m2 BSA sc day 1-5 or 75 mg/m2 BSA sc day 1-5 + 8-9 (to avoid injection during weekends).
Nanexa AB has developed NEX-18a, a subcutaneous injection of azacitidine with extended-release based on the drug delivery system, PharmaShell®. Drug particles are enclosed in a coating with controlled solubility, and as the coating dissolves over time the drug is released in a predefined manner. This technique provides a way to create drugs with a prolonged release for parenteral administration. The technology used by Nanexa to manufacture the coating is via Atomic Layer Deposition (ALD). In ALD, reactive gases are used which build up a surface coating with high precision, atomic layer by atomic layer.
NEX-18a will offer a benefit to current azacitidine treatment with a reduction of subcutaneous administrations, decreased need for pre-medication, and will reduce the time each patient has to spend in the hospital in order to receive the treatment in each cycle. In addition, the patients will spend less time traveling to and from the hospital and from a health care perspective, one injection instead of seven per cycle will reduce the time and the resources the health care provider dedicates to treating the patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azacitidine | Active comparator | Drug: Azacitidine InjectionTreatment phase 1: the patients will receive regular treatment with azacitidine for 4 days. Treatment phase 2: the patients will receive regular treatment with azacitidine for 3 days. |
| NEX-18a | Experimental | Drug: NEX-18a injectionTreatment phase 1: the azacitidine dose for day 5 will be replaced by a single dose NEX-18a Treatment phase 2: the azacitidine dose for day 4 and 5 will be replaced by a single dose NEX-18a |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Provision of written informed consent prior to any study specific procedures.
- Female and male patients ≥ 18 years of age.
- Body Mass Index (BMI) > 19 and < 30 kg/m2 BSA at screening.
- Treatment with azacitidine corresponding to 100 mg/m2 BSA x 5 per treatment cycle for at least six cycles for:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Key exclusion criteria (6 listed)
- The patient has participated in any other investigational/interventional trial including an investigational drug within 30 days (or five half-lives of the study drug prior to screening, whichever is longer) prior to screening.
- Diagnosis of malignant disease within the previous 5 years (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma of the cervix or breast, or other local malignancy excised or irradiated with a high probability of cure).
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
- The patient has a history of alcohol abuse or drug abuse within the past 12 months.
- Any condition including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study.
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 |
|---|---|---|
| NEX-18a injectionAlso: PharmaShell, Azacitidine, 5-azacitidineIn Treatment phase 1, NEX-18a will be given as a single subcutaneous injection. In Treatment phase 2, NEX-18a will be given as a single subcutaneous injection. | Drug | NEX-18a |
| Azacitidine InjectionAlso: Azacitidine, 5-azacitidine, VidazaIn Treatment phase 1, azacitidine will be administered once daily for four days. In Treatment phase 2, azacitidine will be administered once daily for three days. | Drug | Azacitidine |
Primary outcome
Hematology and Clinical Chemistry analyses
Time frame: 0-30 days
Change from baseline to 30 days follow-up. Descriptive individual data.
Adverse events
Time frame: 0-30 days
Change from baseline to 30 days follow-up. Descriptive individual data.
Vital signs
Time frame: 0-30 days
Change from baseline to 30 days follow-up. Descriptive individual data.
Physical examination
Time frame: 0-30 days
Change from baseline to 30 days follow-up. Descriptive individual data.
Local tolerance (injection site)
Time frame: 0-30 days
Change from baseline to 30 days follow-up. Descriptive individual data.
Concomitant medications/therapy
Time frame: 0-30 days
Change from baseline to 30 days follow-up. Descriptive individual data.
9 secondary outcomes
AUC-time curve
Time frame: 0-24 h
AUC from time 0-last
Time frame: 0-336 h
AUC from time 0 to infinity
Time frame: 0-336 h
Plasma Concentration
Time frame: 0-336 h
Plasma Concentration over time
Time frame: 0-336 h
Half-life measurement
Time frame: 0-336 h
Measurement of distribution
Time frame: 0-336 h
Elimination
Time frame: 0-336 h
Local tolerance of NEX-18a
Time frame: 0-30 days
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 17 Oct 2023.
- Individual participant dataSharing planned: No
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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.
Ulla Olsson Strömberg, MD principal investigator
Uppsala University, Uppsala, Sweden
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NEX-18a injection and Azacitidine Injection in people with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML), run by Nanexa AB at 2 sites in Sweden.
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 17 inclusion and 6 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 17 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Hematology and Clinical Chemistry analyses (time frame: 0-30 days). The study lists 6 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 17 Oct 2023; AzTrials last refreshed its copy on 8 Nov 2026.