Clinical trial NCT06439056: Phase 1 Study Assessing the Pharmacokinetics of NEX-22A in Subjects With T2D
Official title: An Open, Single Ascending Dose, Phase 1 Study to Assess the Pharmacokinetics, Safety, and Tolerability of NEX-22A, a Subcutaneous Prolonged-release Injection, in Male and Female Participants With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Type 2 Diabetes
Keywords: Type 2 diabetes
PK study
Long acting injectable
Liraglutid
GLP-1
Lead sponsor: Nanexa AB
Sponsor class: INDUSTRY
Collaborators: name: Profil Institut für Stoffwechselforschung GmbH
First posted: 2024-06-03
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single ascending dose study including 3 cohorts (3 patients/cohort). The subjects will be enrolled in the respective cohorts, starting with cohort 1. NEX-22A will be administered in a sentinel fashion within the cohorts. A single participant will be dosed first in every cohort. If there are no safety concerns as judged by the investigator, the remaining subjects will be dosed at least 10 days after the sentinel.
Primary purpose: TREATMENT

Brief summary: The purpose with the study is to assess pharmacokinetics of NEX-22A in patients with type 2 diabetes.

Detailed description: The trial is a single-centre, open-label, single ascending dose study. After being informed about the study and potential risks, all patients given written informed consent will undergo a screening to determine eligibility for study entry. Each subject will be enrolled in one of the three sequential cohorts, comprising one single dose of NEX-22A liraglutide injection. Each cohort will have a sentinel participant. NEX-22A will be administered in sequential cohorts. Before initiating a new dose cohort, safety, tolerability and PK data for all treated subjects must have been reviewed by the dose escalation committee. Blood samples for PK analysis will be withdrawn at specified timepoints over a period of 36 days

Eligibility criteria: Inclusion Criteria:

1. Signed and dated informed consent obtained before any trial-related activities. Trial-related activities are any procedures that would not have been done during normal management of the subject.
2. Male or female subject with type 2 diabetes mellitus.
3. Metformin therapy without change in dose for the last 3 months.
4. Age between 18 and 65 years, both inclusive.
5. Body Mass Index (BMI) between 18.5 and 35.0 kg/m\^2, both inclusive.
6. HbA1c \&gt; 6.5% and \&lt;= 9.0%.
7. Diabetes duration of at least 1 year.

Exclusion Criteria:

1. Known or suspected hypersensitivity to the IMP or any of the excipients or to any component of the IMP formulation.
2. Previous participation in this trial. Participation is defined as being dosed.
3. Receipt of any medicinal product in clinical development within 30 days or at least 5 half-lives of the related substances and their metabolites (whichever is longer) before enrolment in this trial.
4. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
5. Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the investigator.
6. Clinically relevant comorbidity, capable of constituting a risk for the subject when participating in the trial or of interfering with the interpretation of data.
7. Signs of acute illness as judged by the investigator.
8. Any serious systemic infectious disease during four weeks prior to first dosing of the trial drug, as judged by the investigator.
9. Subjects with dermatological conditions, tattoos or large scars on the abdomen that would limit the evaluation of local tolerability, as judged by the investigator.
10. Clinically significant abnormal values for haematology, biochemistry, coagulation, or urinalysis at screening as judged by the investigator.
11. Systolic blood pressure \&lt; 90 mmHg or \&gt;160 mmHg and/or diastolic blood pressure \&lt; 50 mmHg or \&gt; 95 mmHg at screening (one repeat test will be acceptable in case of suspected white-coat hypertension).
12. Heart rate at rest (as measured in vital sign assessment at screening) outside the range of 50-90 beats per minute.
13. Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the investigator.
14. Proliferative retinopathy or maculopathy as judged by the investigator based on a recent (\&lt;1.5 years) ophthalmologic examination.
15. Severe neuropathy, in particular autonomic neuropathy, as judged by the investigator.
16. Former or current use of liraglutide or any other GLP-1 receptor agonists (exenatide, semaglutide) except for the use in clinical trials.
17. Current use of any insulin or sulfonylureas.
18. Significant history of alcoholism or drug abuse as judged by the investigator or consuming more than 24.0 grams alcohol/day (for males), 12.0 grams alcohol/day (for females) on average.
19. A positive result in the alcohol and/or urine drug screen at the screening visit.
20. Smoking more than 5 cigarettes or the equivalent per day.
21. Inability or unwillingness to refrain from smoking and use of nicotine substitute products one day before and during the inpatient period.
22. Tested positive for hepatitis Bs antigen.
23. Tested positive for hepatitis C antibodies. (Presence of hepatitis C antibodies will not lead to exclusion if liver function tests are normal and a hepatitis C polymerase chain reaction is negative).
24. Positive result to the test for HIV-1/2 antibodies or HIV-1 antigen.
25. Any medication (prescription and non-prescription drugs) within 14 days before IMP administration and/or anticoagulant therapy.
26. Blood donation or blood loss of more than 500 mL within the last 3 months.
27. Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation.
28. Committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
29. Women of childbearing potential.
30. Trial site personnel directly affiliated with this trial and their immediate families (spouse, biological or legal guardian, child, or sibling).
31. The investigator considers a subject as unsuitable for inclusion in the trial for any other reason.

Explanatory note on Exclusion Criterion 25: Exceptions are stable doses of metformin, SGLT2-blockers, low dose aspirin, antihypertensives, statins, thyroid hormones or occasional use of paracetamol or ibuprofen, and ,if female, with the exception of menopausal hormone replacement therapy.

Explanatory note on Exclusion Criterion 29: A woman is considered of childbearing potential following menarche and until becoming postmenopausal unless permanently sterile due to hysterectomy, or bilateral salpingectomy, or bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.

Primary outcomes:
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
measure: To evaluate the PK profile of liraglutide after single ascending doses of NEX-22A in subjects with stable type 2 diabetes
timeFrame: From administration of study drug until 36 days
Secondary outcomes:
measure: Number of subjects with treatment-related adverse events a assessed by frequency
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with treatment-related adverse events a assessed by seriouness
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with treatment-related adverse events a assessed by intensity
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with treatment-related adverse events a assessed by relationship to study treatment
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the systolic blood pressure at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in in the diastolic blood pressure at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the ECG parameter PQ/PR at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the ECG parameter QRS at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the ECG parameter QT at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the ECG parameter QTcB at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the ECG parameter heart rate at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the haematology blood parameters measurements at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the clinical chemistry blood laboratory measurements at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the coagulation blood laboratory measurements at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in plasma glucose measurement at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the head at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the eyes at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the ears at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the nose at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the throat at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the skin and mucosae at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the tyroid at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the neurological status at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the lungs at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the cardiovascular system at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the gastrointestinal system incl mouth at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the physical examination of the lymfh nodes incl mouth at 36 days
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in the musculoskeletal system at 36 days.
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in local tolerability i.e skin reactions assessed by visual inspection.
timeFrame: From administration of study drug until 36 days
measure: Number of subjects with a clinical significant change from baseline in local tolerability i.e skin reactions assessed by photography.
timeFrame: From administration of study drug until 36 days
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil
Study officials:
affiliation: Profil Institut für Stoffwechselforschung GmbH Hellersbergstr. 9 D-41460 Neuss
name: Grit Andersen, MD
role: PRINCIPAL_INVESTIGATOR
References: