HealthyPhase 1NCT05555823

Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Food Effect and DDI of Ascending Doses of the MEK Inhibitor Zapnometinib

A Phase 1 study testing ATR-002, Repaglinide and Celecoxib in people with Healthy, run by Atriva Therapeutics GmbH at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to evaluate the safety and tolerability of ascending doses of the MEK-inhibitor zapnometinib (ATR-002) given as single doses (SAD Part) and as multiple doses for 7 days (MAD Part) in healthy subjects. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: ATR-002, Repaglinide and Celecoxib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 96 participants
Where: 1 siteGermany
Study dates: 23 Jun 2022to 20 Jul 2023
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 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements, prohibitions and restrictions listed in the informed consent form (ICF) and in this protocol.
Subject has been informed both verbally and in writing about the objectives of the clinical trial, the methods, the anticipated benefits and potential risks and the discomfort to which he/she may be exposed, and has given written consent to participation in the trial prior to trial start and any trial-related procedure.
Study participant must be at least 18 years of age and not older than 55 years of age at the time of signing the ICF.
Non-smokers or ex-smokers who had stopped smoking for at least 5 years prior to start of the clinical study.
In good physical and mental health as determined on the basis of medical history and general physical examination performed at screening.
Hematology and chemistry parameters, pulse rate and/or blood pressure, and ECG within the reference range for the population studies, or showing no clinically relevant deviations, as judged by the Investigator (Note that some defined clinical laboratory parameters must not exceed the upper limit of reference range - see Exclusion Criterion #3).

Show all 16Show fewer

Negative urine test for selected drugs of abuse at screening and upon check-in at the clinical site. Note: Subjects should not consume poppy-seeds within 72 h before screening and before each urine drug screening because this can falsify the results of the opiate urine drug test.
Negative alcohol breath test at screening and upon check-in at the clinical site.
Negative hepatitis panel (including hepatitis B surface antigen [HBsAg] and anti-hepatitis C virus [HCV] antibodies) and negative human immunodeficiency virus (HIV) antibody screens and negative SARS-CoV-2 PCR test.
Body weight at least 70 kg for males and 60 kg for females and have a body mass index (BMI) ≥ 18.0 kg/m2 and < 29.9 kg/m2.
Male or female. Pregnancy and Contraception
Female subjects must be of non-childbearing potential, as follows.
A female study participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
At least 1 year post-menopausal (amenorrhea >12 months in the absence of an alternative medical cause and follicle-stimulating hormone >30 mIU/mL in women not using hormonal contraception or hormonal replacement therapy) prior to screening;
Surgically sterile (bilateral oophorectomy, hysterectomy, bilateral salpingectomy, or bilateral tubal ligation).
To protect partners from possible exposure to study medication in semen, male subjects must use a condom during the study, even if they have had a vasectomy or their partner is not of childbearing potential, and they must not plan to father a child, or donate sperm, during the study, and for 4 months after their final dose of study medication. Note: medically acceptable methods of contraception that may be used by the partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, and etonogestrel implant.

Who cannot join

Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-study screening assessment that could interfere with the objectives of the study or the safety of the subject. Note: Blood pressure and heart rate at the screening examination outside the ranges 90- 139 mmHg systolic, 50-89 mmHg diastolic; heart rate 50-90 bpm are considered as exclusion criteria.
QTc interval of ECG above the upper limit of reference range at screening. The following commonly accepted reference range will be taken as a basis: Men: QTc ≤ 440 ms; Women: QTc ≤ 460 ms.
Aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [AP], glutamate dehydrogenase [GLDH], gamma glutamyl transpeptidase [γ-GT]) above the upper limit of the reference range.
Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the study or make it unnecessarily hazardous.
A condition that, in the opinion of the Investigator, could compromise the well-being of the subject or course of the study, or prevent the subject from meeting or performing any study requirements.
Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, cancer, or history of any psychotic mental illness.

Show all 21Show fewer

Respiratory tract infection within 4 weeks before the screening visit.
History of surgery or medical intervention, or planned surgery or medical intervention, that could interfere with the objectives of the study or the safety of the subject.
Presence or history of severe adverse reaction to any drug, or sensitivity to components of the study medication.
Loss of more than 400 mL blood, e.g., as a blood donor, or donation of blood products, during the 3 months before the study.
Positive fecal blood test at screening.
Active or latent parasitic infection, visit to a country with a high prevalence of parasitic infections within 3 months before receiving study medication.
Use of any prescription or over-the-counter medicine, with the exception of acetaminophen (paracetamol), within 14 days (or 5 half-lives, whichever is longer) before the first dose of study medication as defined in Section 10.5.
Treatment with any known enzyme inducing or inhibiting agents (e.g., St. John's Wort (Johanniskraut), barbiturates, phenothiazines, cimetidine, ketoconazole etc.) within 30 days before first administration of IMP or during the trial.
Presence or history of drug or alcohol abuse, or intake of more than 21 units (14 units for women) of alcohol weekly.
Receipt of a living vaccine within the 3 months, or mRNA or vector vaccine against COVID-19 within 4 weeks before dosing, or planned vaccination during the study.
Currently participating in other clinical trials or previous treatment with an investigational medicinal product within 5 half-lives or 30 days (whichever is longer) prior to randomization.
Known allergy or hypersensitivity to the IMP (including excipients) or history of severe adverse reaction to any drug, or sensitivity to components of the study medication.
Study participant is pregnant or breastfeeding.
Subject has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
Subject is an employee of the sponsor, or an employee of any third-party organization involved into the clinical trial, or an employee of the clinical trial site, or is dependent on the investigator.

Trial locations and contacts

1 site in 1 country.

Germany1 site

Atriva study site
Neu-Ulm

Other trials in Germany

About this study

Official title: A Phase I Dose Escalation Study of Ascending Single and Multiple Doses of the MEK Inhibitor Zapnometinib in Healthy Subjects to Evaluate the Safety & Tolerability Compared to Placebo, Additionally Evaluating Pharmacokinetics and Pharmacodynamics of Target Engagement, as Well as Investigating Possible FDI and DDI

Read the detailed description

This is a Phase 1, single-center, randomized, double-blind, controlled clinical trial (zapnometinib vs. placebo in the SAD/MAD Parts; 'fed' vs. 'fasted' in the FDI Part, 'probe substance' (repaglinide or celecoxib) in combination with zapnometinib vs. probe substance alone in the DDI part). The study will assess the safety, tolerability, PK (applicable to SAD/MAD Part) and PD (applicable to SAD Part only) effects of zapnometinib versus a matching placebo (applicable to SAD/MAD Part) in healthy subjects. The FDI cohorts will investigate the possible impact of a standard breakfast high in fat content in comparison to administration in fasted state. The DDI cohorts with celecoxib and repaglinide will investigate a possible drug-drug interaction.

Conditions: Healthy
Being tested: ATR-002, Placebo, Repaglinide, Celecoxib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ATR-002Drug
Also called Zapnometinib
300 mg tablets for oral intake
PlaceboDrug
matching tablets for oral intake
RepaglinideDrug
Also called Repaglinide-ratiopharm
0,5 mg tablets for oral intake
CelecoxibDrug
Also called CELEBREX
100 mg capsules for oral intake

Study groups in NCT05555823
Study group	Role	What they receive
Experimental: ATR-002	Experimental	In the SAD part, study participants will receive IMP orally once (except for the first cohort), or twice (two single doses separated by an adequate washout period of at least 10 days for the FDI cohort, which will be conducted according to a two-period fixed-sequence design with all subjects receiving the treatment sequence 'fasted-fed'). In each of the periods of the MAD Part, study participants will receive the IMP for seven consecutive days. Dosing will start at 600 mg (SAD part) and 900 mg (MAD part) in the first cohort and follow the dose escalation schedule that is given in the study protocol. Receives: Drug: ATR-002
Placebo Comparator: Placebo	Placebo comparator	In the SAD part, study participants will receive IMP orally once (except for the first cohort), or twice (two single doses separated by an adequate washout period of at least 10 days for the FDI cohort, which will be conducted according to a two-period fixed-sequence design with all subjects receiving the treatment sequence 'fasted-fed'). In each of the periods of the MAD Part, study participants will receive the IMP for seven consecutive days. In the DDI period with repaglinide two doses of ATR-002 will be given, and in the DDI period with celecoxib, four doses of ATR-002 will be given. Receives: Drug: Placebo; Drug: Repaglinide; Drug: Celecoxib

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of participants with TEAEs and SAEs, with abnormal ECG readings, abnormal vital signs, and abnormal laboratory parameters
Measured: From 1st administration of study drug (SAD/MAD Day 1; DDI Day -1) up to 21 days after last dosing

Secondary outcomes (23)

SAD part: Cmax
Measured: Day 1 to Day 7
SAD part: tmax
Measured: Day 1 to Day 7
SAD part: t1/2
Measured: Day 1 to Day 7
SAD part: AUC0-t
Measured: Day 1 to Day 7
SAD part: AUC0-∞
Measured: Day 1 to Day 7
MAD part: Cmax
Measured: postdose on Day 1
MAD part: tmax
Measured: postdose on Day 1
MAD part: Ctrough
Measured: Day 2 to Day 7
MAD part: Cmax
Measured: postdose on Day 7
MAD part: tmax
Measured: postdose on Day 7
MAD part: t1/2
Measured: postdose on Day 7
MAD part: AUC0-t
Measured: postdose on Day 7
SAD part: percent MEK inhibition by measuring the reduction of ERK phosphorylation after study drug administration as compared to baseline in stimulated PBMCs isolated from blood samples from study participants
Measured: up to day 5
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): Cmax
Measured: Day 1 to Day 7
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): tmax
Measured: Day 1 to Day 7
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): t1/2
Measured: Day 1 to Day 7
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): AUC0-t
Measured: Day 1 to Day 7
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): AUC0-∞
Measured: Day 1 to Day 7
DDI part: Cmax
Measured: Day -1 and Day 1
DDI part: tmax
Measured: Day -1 and Day 1
DDI part: t1/2
Measured: Day -1 and Day 1
DDI part: AUC0-t
Measured: Day -1 and Day 1
DDI part: AUC0-∞
Measured: Day -1 and Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jun 202220 Jul 2023

First posted27 Sep 2022
Study start23 Jun 2022
Primary completion20 Jul 2023
Study completion20 Jul 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HealthyStudies 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: Other
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized, double-blind, placebo-controlled, mono-centre; SAD, MAD, FDI, DDI part
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 96 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05555823
Sponsor's protocol ID: ATR-002-102
Status last verified: Jul 2023
First submitted: 13 Sep 2022
Last updated: 1 Aug 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Dose Escalation Study of Ascending Single and Multiple Doses of the MEK Inhibitor Zapnometinib in Healthy Subjects to Evaluate the Safety & Tolerability Compared to Placebo, Additionally Evaluating Pharmacokinetics and Pharmacodynamics of Target Engagement, as Well as Investigating Possible FDI and DDI
ClinicalTrials.gov ID: NCT05555823
Acronym / sponsor ID: ATR-002-102
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 96 participants (actual)
Lead sponsor: Atriva Therapeutics GmbHIndustry (pharma, biotech, devices)
Study start: 23 Jun 2022 (actual)
Primary completion: 20 Jul 2023 (actual)
Study completion: 20 Jul 2023 (actual)
First posted: 27 Sep 2022 (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.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2
Model description: Randomized, double-blind, placebo-controlled, mono-centre; SAD, MAD, FDI, DDI part

Arm	Type	Receives
Experimental: ATR-002	Experimental	Drug: ATR-002In the SAD part, study participants will receive IMP orally once (except for the first cohort), or twice (two single doses separated by an adequate washout period of at least 10 days for the FDI cohort, which will be conducted according to a two-period fixed-sequence design with all subjects receiving the treatment sequence 'fasted-fed'). In each of the periods of the MAD Part, study participants will receive the IMP for seven consecutive days. Dosing will start at 600 mg (SAD part) and 900 mg (MAD part) in the first cohort and follow the dose escalation schedule that is given in the study protocol.
Placebo Comparator: Placebo	Placebo comparator	Drug: Placebo, Drug: Repaglinide, Drug: CelecoxibIn the SAD part, study participants will receive IMP orally once (except for the first cohort), or twice (two single doses separated by an adequate washout period of at least 10 days for the FDI cohort, which will be conducted according to a two-period fixed-sequence design with all subjects receiving the treatment sequence 'fasted-fed'). In each of the periods of the MAD Part, study participants will receive the IMP for seven consecutive days. In the DDI period with repaglinide two doses of ATR-002 will be given, and in the DDI period with celecoxib, four doses of ATR-002 will be given.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (16 listed)

Capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements, prohibitions and restrictions listed in the informed consent form (ICF) and in this protocol.
Subject has been informed both verbally and in writing about the objectives of the clinical trial, the methods, the anticipated benefits and potential risks and the discomfort to which he/she may be exposed, and has given written consent to participation in the trial prior to trial start and any trial-related procedure.
Study participant must be at least 18 years of age and not older than 55 years of age at the time of signing the ICF.
Non-smokers or ex-smokers who had stopped smoking for at least 5 years prior to start of the clinical study.
In good physical and mental health as determined on the basis of medical history and general physical examination performed at screening.

Key exclusion criteria (21 listed)

Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-study screening assessment that could interfere with the objectives of the study or the safety of the subject. Note: Blood pressure and heart rate at the screening examination outside the ranges 90- 139 mmHg systolic, 50-89 mmHg diastolic; heart rate 50-90 bpm are considered as exclusion criteria.
QTc interval of ECG above the upper limit of reference range at screening. The following commonly accepted reference range will be taken as a basis: Men: QTc ≤ 440 ms; Women: QTc ≤ 460 ms.
Aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [AP], glutamate dehydrogenase [GLDH], gamma glutamyl transpeptidase [γ-GT]) above the upper limit of the reference range.
Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the study or make it unnecessarily hazardous.
A condition that, in the opinion of the Investigator, could compromise the well-being of the subject or course of the study, or prevent the subject from meeting or performing any study requirements.

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
ATR-002Also: Zapnometinib300 mg tablets for oral intake	Drug	Experimental: ATR-002
Placebomatching tablets for oral intake	Drug	Placebo Comparator: Placebo
RepaglinideAlso: Repaglinide-ratiopharm0,5 mg tablets for oral intake	Drug	Placebo Comparator: Placebo
CelecoxibAlso: CELEBREX100 mg capsules for oral intake	Drug	Placebo Comparator: Placebo

Primary outcome

Number of participants with TEAEs and SAEs, with abnormal ECG readings, abnormal vital signs, and abnormal laboratory parameters
Time frame: From 1st administration of study drug (SAD/MAD Day 1; DDI Day -1) up to 21 days after last dosing

23 secondary outcomes

SAD part: Cmax
Time frame: Day 1 to Day 7
SAD part: tmax
Time frame: Day 1 to Day 7
SAD part: t1/2
Time frame: Day 1 to Day 7
SAD part: AUC0-t
Time frame: Day 1 to Day 7
SAD part: AUC0-∞
Time frame: Day 1 to Day 7
MAD part: Cmax
Time frame: postdose on Day 1
MAD part: tmax
Time frame: postdose on Day 1
MAD part: Ctrough
Time frame: Day 2 to Day 7
MAD part: Cmax
Time frame: postdose on Day 7
MAD part: tmax
Time frame: postdose on Day 7
MAD part: t1/2
Time frame: postdose on Day 7
MAD part: AUC0-t
Time frame: postdose on Day 7
SAD part: percent MEK inhibition by measuring the reduction of ERK phosphorylation after study drug administration as compared to baseline in stimulated PBMCs isolated from blood samples from study participants
Time frame: up to day 5
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): Cmax
Time frame: Day 1 to Day 7
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): tmax
Time frame: Day 1 to Day 7
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): t1/2
Time frame: Day 1 to Day 7
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): AUC0-t
Time frame: Day 1 to Day 7
FDI cohort (two-period fixed-sequence design 'fasted' vs. 'fed'): AUC0-∞
Time frame: Day 1 to Day 7
DDI part: Cmax
Time frame: Day -1 and Day 1
DDI part: tmax
Time frame: Day -1 and Day 1
DDI part: t1/2
Time frame: Day -1 and Day 1
DDI part: AUC0-t
Time frame: Day -1 and Day 1
DDI part: AUC0-∞
Time frame: Day -1 and Day 1

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 Aug 2023.

Related trials for Healthy

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

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.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ATR-002, Repaglinide and Celecoxib in people with Healthy, run by Atriva Therapeutics GmbH at 1 site in Germany.

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 16 inclusion and 21 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 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. 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. Some participants in this study may receive a placebo. 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?

Number of participants with TEAEs and SAEs, with abnormal ECG readings, abnormal vital signs, and abnormal laboratory parameters (time frame: From 1st administration of study drug (SAD/MAD Day 1; DDI Day -1) up to 21 days after last dosing). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05555823.

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 Aug 2023.