COVID-19Phase 2RESPIRENCT04776044
Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients With COVID-19
A Phase 2 study testing ATR-002 in people with COVID-19, run by Atriva Therapeutics GmbH at 40 sites in 7 countries.
Trial summary
The purpose of the study is to assess the safety and efficacy of ATR-002 (in addition to standard-of-care) for the treatment of COVID-19 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- ATR-002
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 133 participants
- Where
- 40 sitesin 7 countries
- Study dates
- 12 Apr 2021to 9 Aug 2022
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Study participant must be at least 18 years of age at the time of signing the ICF
- Study participants with a laboratory confirmed diagnosis of SARS-CoV-2 infection presenting as moderate -to-severe COVID-19 requiring hospitalization for COVID-19 (Clinical Severity Status [3] or [4]) and for medical reasons (see Section 8). Patients presenting to the hospital without a laboratory confirmed SARS-CoV-2 infection will be tested locally for SARS-CoV-2 during the screening period. For sites in the EU: A CE certified SARS-CoV-2 PCR test kit is required to confirm infection. For sites outside the EU: SARS-CoV-2 PCR test kits certified according to local regulations are required to confirm infection.
- Body weight at least 50 kg and a body mass index (BMI) ≥ 18.0 kg/m2 and < 40.0 kg/m2
- Male or female Contraceptive use by women and men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- A female study participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
Show all 17Show fewer
- She is not a WOCBP
- Is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, during the IMP period and for at least 4 weeks after the last dose of IMP. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of IMP.
- A WOCBP must have a negative urine pregnancy test within 24 hours before the first dose of IMP.
- If a urine pregnancy test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required locally. In such cases, the participant must not be randomized if the serum pregnancy result is positive.
- If a serum pregnancy test is required as per local regulations, a serum pregnancy test is required locally. In such cases, the participant must not be randomized if the serum pregnancy result is positive.
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetectable pregnancy.
- A male study participant is eligible to participate if:
- He is azoospermic
- The partner is not a WOCBP.
- The partner is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, during the IMP period and for at least 90 days after the last dose of IMP. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of IMP.
- He acknowledges that sperm donation is prohibited from the first dose of IMP until at least 90 days after the last dose of IMP.
Who cannot join
- Patient's clinical condition is worsening rapidly.
- Requiring ICU admission or ventilator support at screening or at randomization.
- Suspected bacterial, fungal, viral, or other infection (besides COVID-19).
- History of any of the following: malignant disease, autoimmune disease, or severe liver, kidney, blood, cardiac, pulmonary, neurological, or endocrine disease as judged by the investigator.
- History of hypertension should have hypertension adequately controlled (BP < 140/90 mmHg) with appropriate anti-hypertensive treatment.
- Clinically significant cardiac conduction abnormalities, including QTc prolongation of > 450 milliseconds
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- Family history of Long QT Syndrome.
- Heart failure class 3, or 4, as defined by the New York Heart Association (NYHA).
- History of acute coronary syndrome (including myocardial infarction), coronary angioplasty, or stenting within 24 weeks prior to screening.
- Patients with implanted defibrillators or permanent pacemakers.
- Poorly controlled diabetes mellitus with an HbA1c > 7.5 %.
- Renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome, or renal tubular acidosis.
- Renal failure requiring renal replacement therapy or moderate renal impairment as defined by having an estimated glomerular filtration rate (eGFR, CKD-EPI) < 45 ml/min/1.73m2.
- Chronic Obstructive Pulmonary Disease (COPD) GOLD C, or D, or hospitalization for exacerbation of COPD within 24 weeks prior to screening.
- Other chronic lung diseases including cystic fibrosis, neuromuscular diseases, severe chest wall deformities, interstitial lung diseases, outpatient chronic non-invasive ventilation due to chronic respiratory failure.
- Asthma with a symptom control level of "uncontrolled", according to current GINA guidelines.
- Currently suffering from diseases that seriously affect the immune system, such as: human immunodeficiency virus (HIV) infection, or the blood system, or splenectomy, or organ/ stem cell transplantation.
- Known Hepatitis B or C infection.
- Any medical condition, physical examination finding or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient.
- Alanine transaminase (ALT) or aspartate transaminase (AST) >3.0 x ULN.
- Total bilirubin >1.0 x ULN (≥1.5 x ULN total bilirubin if known Gilbert's syndrome).
- Taking concomitant medication metabolized by CYP2C8 and/ or CYP2C9.
- Taking concomitant medication of any experimental treatment or use of marketed medications including off-label use, that are intended as specific treatment for COVID-19. Any such treatments must be washed out for 30 days or at least 5 half-lives prior to randomization, whichever is longer, unless a formal written standard of care policy document requires otherwise. Inclusion needs to be approved by the investigator and medical monitor.
- Taking medication that may seriously affect the immune system, e.g., chemotherapy, unless considered and documented as standard of care (e.g., corticosteroids) to treat COVID-19.
- 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).
- Study participant is pregnant or breastfeeding.
- Patient has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
- Patient 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
40 sites in 7 countries.
40 sites in 7 countries
Germany10 sites
Atriva study site 49006
Augsburg
Atriva study site 49001
Berlin
Atriva study site 49013
Berlin
Atriva study site 49011
Dresden
Atriva study site 49003
Frankfurt
Atriva study site 49008
Frankfurt
Atriva study site 49009
Freiburg im Breisgau
Atriva study site 49007
Halle
Atriva study site 49004
Münster
Atriva study site 49012
Rostock
India7 sites
Atriva study site 91002
Ahmedabad
Atriva study site 91001
Aligarh
Atriva study site 91011
Chhatrapati Sambhajinagar
Atriva study site 91008
Mumbai
Atriva study site 91009
Mumbai
Atriva study site 91003
New Delhi
Atriva study site 91004
Raipur
Spain7 sites
Atriva study site 34001
Barcelona
Atriva study site 34011
Lleida
Atriva study site 34002
Madrid
Atriva study site 34005
Madrid
Atriva study site 34008
Madrid
Atriva study site 34010
Pontevedra
Atriva study site 34004
Valencia
South Africa6 sites
Atriva study site 27005
Benoni
Atriva study site 27002
Cape Town
Atriva study site 27003
George
Atriva study site 27006
KwaZulu
Atriva study site 27007
Mayville
Atriva study site 27008
Pretoria
Romania5 sites
Atriva study site 40006
Bucharest
Atriva study site 40002
Iași
Atriva study site 40004
Sibiu
Atriva study site 40008
Suceava
Atriva study site 40003
Timișoara
Poland3 sites
Atriva study site 48002
Bolesławiec
Atriva study site 48004
Bolesławiec
Atriva study site 48003
Warsaw
Netherlands2 sites
Atriva study site 31001
Eindhoven
Atriva study site 31002
Tilburg
About this study
Official title: RESPIRE - A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients With COVID-19
The purpose of the study is to assess the safety and efficacy of ATR-002 (in addition to standard-of-care) for the treatment of COVID-19
Read the detailed description
After being informed about the study and potential risks, all patients giving written informed consent will be undergoing a 1-day screening to determine eligibility for study entry. At day 1, patients who meet the eligibility requirements will be randomized in a double-blind manner (participant and investigator) in a 1:1 ratio to ATR-002 (900mg day 1, 600mg days 2 - 6) or placebo (once daily)
- Conditions
- COVID-19
- Being tested
- ATR-002, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATR-002Drug
150mg tablets for oral intake
PlaceboDrug
matching tablets for oral intake
| Study group | Role | What they receive |
|---|---|---|
| ATR-002 | Experimental | Participants will receive 900mg ATR-002 on day 1 (6 tablets with 150mg ATR-002; once daily), and 600mg ATR-002 on days 2 - 6 (4 tablets; once daily) Receives: Drug: ATR-002 |
| Placebo | Placebo comparator | Participants will receive matching tablets placebo on day 1 (6 tablets, once daily), and matching tablets placebo on days 2 - 6 (4 tablets per day, once daily) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical severity status on a 7-point ordinal scale
- Not hospitalized, no limitations of activities
- Not hospitalized, limitations of activities
- Hospitalized, not requiring supplemental oxygen
- Hospitalized, requiring supplemental oxygen
- Hospitalized, on non-invasive ventilation or high flow oxygen devices
- Hospitalized, on invasive mechanical ventilation or ECMO
- Death
Measured: 15 days
Secondary outcomes (5)
Time from randomization to discharge from hospital
Measured: 90 days
Time to discharge from hospital or to score of ≤2 maintained for 24 hours in NEWS2, whichever occurs first
Measured: 90 days
Time to resolution of fever, defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic) for at least 24 hours without antipyretics for 24 hours
Measured: 90 days
Time to SpO2 >94% on room air maintained for 24 hours
Measured: 90 days
Clinical severity status over the hospital period calculated as AUC from the 7-point ordinal scale at Days 3, 5, 8, 11, 15 and 30
Measured: at days 3, 5, 8, 11 and 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2021
- Study start12 Apr 2021
- Primary completion6 Jun 2022
- Study completion9 Aug 2022
Why it stopped: general circumstances around COVID-19 and current availability of hospitalized patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies 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
- Parallel groups
- Model description
- Randomized, double-blind, placebo-controlled, multi-centre
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 133 participants (actual)
Sponsor and investigators
- Lead sponsor
- Atriva Therapeutics GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- University Clinic Frankfurt M Medical Clinic, Principal investigator, Centre of Pneumology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04776044
- Sponsor's protocol ID
- ATR-002-202
- Acronym
- RESPIRE
- Status last verified
- Sep 2022
- First submitted
- 26 Feb 2021
- Last updated
- 22 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rohde G, Stenglein S, Prozesky H, Manudhane G, Sandulescu O, Bauer M, Overend T, Koch W, Neuschwander D, Planz O, Torres A, Witzenrath M. Efficacy and safety of zapnometinib in hospitalised adult patients with COVID-19 (RESPIRE): a randomised, double-blind, placebo-controlled, multicentre, proof-of-concept, phase 2 trial. EClinicalMedicine. 2023 Oct 4;65:102237. doi: 10.1016/j.eclinm.2023.102237. eCollection 2023 Nov.
PubMed 38106555
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RESPIRE - A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients With COVID-19
- ClinicalTrials.gov ID
- NCT04776044
- Acronym / sponsor ID
- RESPIRE / ATR-002-202
- Conditions
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: general circumstances around COVID-19 and current availability of hospitalized patients
- Enrolment
- 133 participants (actual)
- Lead sponsor
- Atriva Therapeutics GmbHIndustry (pharma, biotech, devices)
- Study start
- 12 Apr 2021 (actual)
- Primary completion
- 6 Jun 2022 (actual)
- Study completion
- 9 Aug 2022 (actual)
- First posted
- 1 Mar 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 purpose of the study is to assess the safety and efficacy of ATR-002 (in addition to standard-of-care) for the treatment of COVID-19
Detailed description
After being informed about the study and potential risks, all patients giving written informed consent will be undergoing a 1-day screening to determine eligibility for study entry. At day 1, patients who meet the eligibility requirements will be randomized in a double-blind manner (participant and investigator) in a 1:1 ratio to ATR-002 (900mg day 1, 600mg days 2 - 6) or placebo (once daily)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized, double-blind, placebo-controlled, multi-centre
| Arm | Type | Receives |
|---|---|---|
| ATR-002 | Experimental | Drug: ATR-002Participants will receive 900mg ATR-002 on day 1 (6 tablets with 150mg ATR-002; once daily), and 600mg ATR-002 on days 2 - 6 (4 tablets; once daily) |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive matching tablets placebo on day 1 (6 tablets, once daily), and matching tablets placebo on days 2 - 6 (4 tablets per day, once daily) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Study participant must be at least 18 years of age at the time of signing the ICF
- Study participants with a laboratory confirmed diagnosis of SARS-CoV-2 infection presenting as moderate -to-severe COVID-19 requiring hospitalization for COVID-19 (Clinical Severity Status [3] or [4]) and for medical reasons (see Section 8). Patients presenting to the hospital without a laboratory confirmed SARS-CoV-2 infection will be tested locally for SARS-CoV-2 during the screening period. For sites in the EU: A CE certified SARS-CoV-2 PCR test kit is required to confirm infection. For sites outside the EU: SARS-CoV-2 PCR test kits certified according to local regulations are required to confirm infection.
- Body weight at least 50 kg and a body mass index (BMI) ≥ 18.0 kg/m2 and < 40.0 kg/m2
- Male or female Contraceptive use by women and men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Key exclusion criteria (29 listed)
- Patient's clinical condition is worsening rapidly.
- Requiring ICU admission or ventilator support at screening or at randomization.
- Suspected bacterial, fungal, viral, or other infection (besides COVID-19).
- History of any of the following: malignant disease, autoimmune disease, or severe liver, kidney, blood, cardiac, pulmonary, neurological, or endocrine disease as judged by the investigator.
- History of hypertension should have hypertension adequately controlled (BP < 140/90 mmHg) with appropriate anti-hypertensive treatment.
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-002150mg tablets for oral intake | Drug | ATR-002 |
| Placebomatching tablets for oral intake | Drug | Placebo |
Primary outcome
Clinical severity status on a 7-point ordinal scale
Time frame: 15 days
1. Not hospitalized, no limitations of activities 2. Not hospitalized, limitations of activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death
5 secondary outcomes
Time from randomization to discharge from hospital
Time frame: 90 days
Time to discharge from hospital or to score of ≤2 maintained for 24 hours in NEWS2, whichever occurs first
Time frame: 90 days
Time to resolution of fever, defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic) for at least 24 hours without antipyretics for 24 hours
Time frame: 90 days
Time to SpO2 >94% on room air maintained for 24 hours
Time frame: 90 days
Clinical severity status over the hospital period calculated as AUC from the 7-point ordinal scale at Days 3, 5, 8, 11, 15 and 30
Time frame: at days 3, 5, 8, 11 and 30
Results and safety
The study was stopped early (reason given: general circumstances around COVID-19 and current availability of hospitalized patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2022.
- Derived from this study: PubMed 38106555Rohde G, Stenglein S, Prozesky H, Manudhane G, Sandulescu O, Bauer M, Overend T, Koch W, Neuschwander D, Planz O, Torres A, Witzenrath M. Efficacy and safety of zapnometinib in hospitalised adult patients with COVID-19 (RESPIRE): a randomised, double-blind, placebo-controlled, multicentre, proof-of-concept, phase 2 trial. EClinicalMedicine. 2023 Oct 4;65:102237. doi: 10.1016/j.eclinm.2023.102237. eCollection 2023 Nov.
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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.
University Clinic Frankfurt M Medical Clinic principal investigator
Centre of Pneumology
40 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATR-002 in people with COVID-19, run by Atriva Therapeutics GmbH at 40 sites in 7 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 17 inclusion and 29 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: stopped early, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in Germany, India, Spain, South Africa, Romania and 2 more countries. 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 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 was stopped early (reason given: general circumstances around COVID-19 and current availability of hospitalized patients). Results are not available in the source record.
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?
Clinical severity status on a 7-point ordinal scale (time frame: 15 days). 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 NCT04776044, which also lists 1 linked publication.
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 22 Sep 2022.