A study to compare the effects and safety of gadoquatrane with an already used available contrast agent for MRI tests in people with any known or suspected problems (except brain or spinal cord-related problems)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bayer AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Trial duration

20 Sep 2023 → 21 Dec 2024

Decision date (initial)

2023-08-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bayer AG, Leverkusen, Germany

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Diagnosis, Efficacy

To demonstrate non-inferior efficacy of gadoquatrane compared to macrocyclic GBCAs

Secondary objectives 6

1. To demonstrate non-inferior diagnostic performance of gadoquatrane compared to macrocyclic GBCAs
2. To demonstrate superior efficacy of gadoquatrane compared to unenhanced MRI
3. To describe diagnostic performance based on CE MRIs with gadoquatrane compared to macrocyclic GBCAs
4. To describe efficacy based on CE MRIs with gadoquatrane compared to macrocyclic GBCAs
5. To evaluate the number of lesions with gadoquatrane enhanced MRI compared to unenhanced imaging and to macrocyclic GBCAs
6. To demonstrate similar overall safety profile of 0.04 mmol Gd/kg gadoquatrane compared to 0.1 mmol Gd/kg of macrocyclic GBCAs

Conditions and MedDRA coding

Contrast enhancement in magnetic resonance imaging for assessment of non-central nervous system pathology

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002778-PIP01-20

Plan to share IPD

No

IPD plan description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participant must be >= 18 years of age inclusive, at the time of signing the informed consent form.
2. Participants with a clinical indication for a contrast-enhanced MRI (including MRA), with any approved standard of care macrocyclic GBCA with proven efficacy, safety and tolerability in clinical routine CE-MRI/MRA (gadobutrol, gadoterate meglumine/ gadoteric acid or gadoteridol) that is used at the site for the indication, with known or suspected pathology of any body region, e.g. head and neck (except CNS), thorax (including e.g. breast, heart, chest wall), abdomen (including e.g. liver, kidney, pancreas), pelvis (including e.g. prostate, uterus, ovaries), extremities (including upper and lower.
3. Participants who can undergo study-related procedures, including 2 contrast-enhanced MRI examinations (one with gadoquatrane and one with a comparator macrocyclic GBCA), as per participant and Investigator’s judgement.
4. Contraceptive use by female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of nonchildbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method during the study intervention period (at a minimum of 24 hours after the last dose of study intervention).

Exclusion criteria 10

1. Considered clinically unstable or has a concurrent/concomitant condition that may significantly alter image comparability between the 2 study MRIs or between study parameters (e.g. safety, PK parameters) or would not allow participation for the full planned study period, in the judgement of the investigator.
2. Participants presenting with severe renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2, derived from a serum or plasma creatinine sample obtained within 48 hours prior to the first contrast agent injection in the study.
3. Participants with acute kidney injury (i.e., acute renal failure), regardless of eGFR
4. History of moderate to severe allergic-like reaction to any GBCA
5. Bronchial asthma considered unstable or who have had recent modification to their medical therapy
6. Receipt of any contrast agent < 72 h prior to the study MRIs or planned to receive any contrast agent during the trial until 24 h +/- 4 h after the second study MRI.
7. Planned or expected interventional diagnostic or therapeutic procedure (e.g. biopsy or surgery in the region of interest) or change in treatment (e.g. start of chemotherapy or antiangiogenic therapy, significant change in corticosteroids dose) that may significantly alter image comparability between the 2 MRIs or other study parameters (i.e. safety/AEs [e.g. confounding AEs or safety events due to surgery or chemotherapy], PK parameters), from the first study MRI up to 24 h after the second study MRI.
8. Has received any investigational product within 30 days, or within 5 times half-life of the investigational product, whatever is shorter, prior to or concurrent with this study.
9. Contraindications to the administration of macrocyclic GBCAs (depending on local product label), or history of adverse reaction to gadoquatrane.
10. Any contraindication to MRI examinations based on institution policy and investigator’s clinical judgement (e.g. some metallic implants or active implants)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 3 visualization parameters (enhancement on a 4PS, delineation on a 4PS, morphology on a 3PS) assessed by separate blinded evaluation of combined pre- and post- gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR

Secondary endpoints 9

1. Sensitivity and specificity for the detection of lesions of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
2. 3 visualization parameters (enhancement on a 4PS, delineation on a 4PS, morphology on a 3PS) assessed by separate blinded evaluation of unenhanced and combined pre- and post-gadoquatrane MRI, by a BICR
3. The overall diagnostic clinical value of combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, based on i. the evaluation of diagnostic descriptive imaging features adapted from radiologic reporting standards (detection/exclusion of enhancing pathology; location, extent, and pattern of enhancement) on a 5PS (by BICR and Investigator); ii. the evaluation of patient management based on the diagnostic reporting recommendations (by Investigator)
4. Sensitivity and specificity for the detection of malignant lesions of combined pre- and post-gadoquatrane MRI and combined pre- and post-contrastcomparator MRI with macrocyclic GBCAs assessed by BICR and the investigator
5. Describe the diagnoses from combined pre- and post- gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs by the Investigator
6. Confidence in diagnosis combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs by BICR and by Investigator on 4PS.
7. Number of lesions seen on unenhanced MR image set and combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
8. Number of enhancing lesions seen on combined pre- and post-gadoquatrane MRI and combined pre- and post-comparator MRI with macrocyclic GBCAs, by a BICR
9. Number and intensity of treatment emergent adverse events, including number of serious adverse events, after administration of gadoquatrane compared to macrocyclic GBCAs reported by the investigator during 24 ±4h p.i.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bayer AG

Sponsor organisation

Bayer AG

City

Leverkusen

Postcode

51368

Country

Germany

Scientific contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Public contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Third parties 2

Locations

8 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications