Pharmacokinetics, Tolerability and Safety of NEX-18a

NCT05048498 | Completed Phase 1

• 1 other identifier: NEX-18-01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Myelodysplastic Syndromes (MDS); Chronic Myelomonocytic Leukemia (CMML); Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (6)

• Hematology and Clinical Chemistry analyses

  Change from baseline to 30 days follow-up. Descriptive individual data.

  0-30 days

• Adverse events

  Change from baseline to 30 days follow-up. Descriptive individual data.

  0-30 days

• Vital signs

  Change from baseline to 30 days follow-up. Descriptive individual data.

  0-30 days

• Physical examination

  Change from baseline to 30 days follow-up. Descriptive individual data.

  0-30 days

• Local tolerance (injection site)

  Change from baseline to 30 days follow-up. Descriptive individual data.

  0-30 days

• Concomitant medications/therapy

  Change from baseline to 30 days follow-up. Descriptive individual data.

  0-30 days

Secondary Outcomes (9)

• AUC-time curve

  0-24 h

• AUC from time 0-last

  0-336 h

• AUC from time 0 to infinity

  0-336 h

• Plasma Concentration

  0-336 h

• Plasma Concentration over time

  0-336 h

Study Arms (2)

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.

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

Drug: NEX-18a injection

Interventions

NEX-18a injection DRUG

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.

Also known as: PharmaShell, Azacitidine, 5-azacitidine

NEX-18a

Azacitidine Injection DRUG

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.

Also known as: Azacitidine, 5-azacitidine, Vidaza

Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nanexa AB: lead
• Uppsala University: collaborator

Study Sites (2)

Karolinska University Hospital Huddinge

Huddinge, Sweden

Location

Kliniska Forsknings och Utvecklings Enheten KFUE

Uppsala, Sweden

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Ulla Olsson Strömberg, MD

  Uppsala University, Uppsala, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: September 17, 2021
• Study Start: April 27, 2021
• Primary Completion: February 10, 2022
• Study Completion: February 10, 2022
• Last Updated: October 17, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)