Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients With COVID-19

NCT04776044 | Terminated Phase 2 DMC

• 1 other identifier: ATR-002-202
• Study Type: interventional
• Target: 133
• Locations: 7 countries
• Sites: 40

Brief 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

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• Clinical severity status on a 7-point ordinal scale

  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

  15 days

Secondary Outcomes (5)

• Time from randomization to discharge from hospital

  90 days

• Time to discharge from hospital or to score of ≤2 maintained for 24 hours in NEWS2, whichever occurs first

  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

  90 days

• Time to SpO2 >94% on room air maintained for 24 hours

  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

  at days 3, 5, 8, 11 and 30

Study Arms (2)

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)

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)

Drug: Placebo

Interventions

ATR-002 DRUG

150mg tablets for oral intake

ATR-002

Placebo DRUG

matching tablets for oral intake

Placebo

Eligibility Criteria

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

You may qualify if:

• 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:
• 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.
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Atriva Therapeutics GmbH: lead

Study Sites (40)

Atriva study site 49006

Augsburg, Germany

Location

Atriva study site 49001

Berlin, Germany

Location

Atriva study site 49013

Berlin, Germany

Location

Atriva study site 49011

Dresden, Germany

Location

Atriva study site 49003

Frankfurt, Germany

Location

Atriva study site 49008

Frankfurt, Germany

Location

Atriva study site 49009

Freiburg im Breisgau, Germany

Location

Atriva study site 49007

Halle, Germany

Location

Atriva study site 49004

Münster, Germany

Location

Atriva study site 49012

Rostock, Germany

Location

Atriva study site 91002

Ahmedabad, India

Location

Atriva study site 91001

Aligarh, India

Location

Atriva study site 91011

Aurangabad, India

Location

Atriva study site 91008

Mumbai, India

Location

Atriva study site 91009

Mumbai, India

Location

Atriva study site 91003

New Delhi, India

Location

Atriva study site 91004

Raipur, India

Location

Atriva study site 31001

Eindhoven, Netherlands

Location

Atriva study site 31002

Tilburg, Netherlands

Location

Atriva study site 48002

Bolesławiec, Poland

Location

Atriva study site 48004

Bolesławiec, Poland

Location

Atriva study site 48003

Warsaw, Poland

Location

Atriva study site 40006

Bucharest, Romania

Location

Atriva study site 40002

Iași, Romania

Location

Atriva study site 40004

Sibiu, Romania

Location

Atriva study site 40008

Suceava, Romania

Location

Atriva study site 40003

Timișoara, Romania

Location

Atriva study site 27005

Benoni, South Africa

Location

Atriva study site 27002

Cape Town, South Africa

Location

Atriva study site 27003

George, South Africa

Location

Atriva study site 27006

KwaZulu, South Africa

Location

Atriva study site 27007

Mayville, South Africa

Location

Atriva study site 27008

Pretoria, South Africa

Location

Atriva study site 34001

Barcelona, Spain

Location

Atriva study site 34011

Lleida, Spain

Location

Atriva study site 34002

Madrid, Spain

Location

Atriva study site 34005

Madrid, Spain

Location

Atriva study site 34008

Madrid, Spain

Location

Atriva study site 34010

Pontevedra, Spain

Location

Atriva study site 34004

Valencia, Spain

Location

Related Publications (1)

• 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.

  PMID: 38106555 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

2-(2-chloro-4-iodophenylamino)-N-3,4-difluorobenzoic acid

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• University Clinic Frankfurt M Medical Clinic

  Centre of Pneumology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: matching placebo tablets
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, multi-centre

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: March 1, 2021
• Study Start: April 12, 2021
• Primary Completion: June 6, 2022
• Study Completion: August 9, 2022
• Last Updated: September 22, 2022

Record last verified: 2022-09

Locations

NL (2); DE (10); ZA (6); ES (7); PL (3); RO (5); IN (7)