A Phase 3 efficacy and safety study of fosmanogepix for the treatment of adult participants with candidemia and/or invasive candidiasis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Basilea Pharmaceutica International AG Allschwil

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

11 Dec 2024 → ongoing

Decision date (initial)

2025-01-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Basilea Pharmaceutica International Ltd, Allschwil · Biomedical Advanced Research and Development Authority (BARDA), United States of America

External identifiers

EU CT number

2022-500455-23-00

ClinicalTrials.gov

NCT05421858

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacokinetic

To evaluate the efficacy of IV followed by oral fosmanogepix in the treatment of adult patients with candidemia and/or invasive candidiasis, by comparison to a standard-of-care regimen of IV caspofungin followed by oral fluconazole.

Secondary objectives 4

1. 1. To evaluate the efficacy of fosmanogepix compared to caspofungin/fluconazole based on independent AC-assessed overall response, clinical and mycological response at different timepoints.
2. 2. To evaluate the time to first negative blood culture for patients with baseline candidemia
3. 3. To evaluate the safety and tolerability of IV followed by oral fosmanogepix in the treatment of adult patients with candidemia and/or invasive candidiasis, by comparison to a standard of care regimen of IV caspofungin followed by oral fluconazole.
4. 4. To evaluate the PK of fosmanogepix (prodrug) and manogepix (active moiety).

Conditions and MedDRA coding

Candidemia

Regulatory references

Scientific advice from competent authorities

The Spanish Agency Of Medicines And Medical Devices, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1. Patients ≥18 years (or the minimum country-specific age of consent if > 18) at Screening who have provided signed informed consent indicating that they understand the purpose of, and procedures required for, the study, and are willing to participate in the study. If the patient is unable to consent for himself/herself, a legally authorized representative must provide informed consent on his/her behalf.
2. 2. Diagnosis of candidemia and/or invasive candidiasis based on a blood or non-blood specimen obtained within ≤96 hours (4 days) before randomization, and on clinical criteria judged attributable to candidemia/invasive candidiasis occurring at any time from ≤ 12 hours prior to the qualifying positive index culture being taken through to randomization.
3. 3. Patient's condition allows for appropriate infection source control measures, including removal of pre-existing intravascular catheters and devices, if necessary.

Exclusion criteria 14

1. 1. Existing Infection a) Infection known to be due to Candida, in blood or any other normally sterile site. b) Inappropriate fungal infection source control. c) Diagnosis of certain deep-seated Candida infections.
2. 2. Life expectancy of <72 hours in the opinion of the investigator.
3. 3. Requirement, or expected requirement, for hemodialysis, peritoneal dialysis, or hemofiltration.
4. 4. Ongoing neurological disorders, including specified conditions presenting with a CTCAE Grade ≥ 2.
5. 5. Patients with known human immunodeficiency virus infection who have CD4+ count <200/mm3 or viral load >400 copies/mL, or who have had an active opportunistic infection within 6 months prior to Screening.
6. 6. Other medical or psychiatric condition or laboratory abnormality that may increase the risk of study participation or make the patient inappropriate for the study.
7. 7. Current use of any prohibited concomitant medications or those unwilling/unable to use a permitted concomitant medications.
8. 8. Received > 2 days (> 48 hours) equivalent of prior systemic antifungal treatment at approved dose and frequency to treat the current episode of candidemia and/or invasive candidiasis (e.g., > 2 doses of a once daily antifungal agent or > 4 doses of a twice daily antifungal agent), within the 96 hours prior to randomization (except for non-susceptible Candida spp. and for patients who develop candidemia or invasive candidiasis while on prophylaxis with an azole or amphotericin B).
9. 9. Previous administration with an investigational drug or investigational vaccine within 30 days or 5 half-lives preceding the first dose of study drug used in this study (whichever is longer).
10. 10. Prior participation in this or any previous study of fosmanogepix.
11. 11. Moderate or severe hepatic impairment, known active viral hepatitis B or C, ALT or AST ≥ 5 × ULN or total bilirubin > 3 × ULN unless this is due to isolated hyperbilirubinemia or documented Gilbert`s syndrome.
12. 12. Female patient is pregnant or lactating.
13. 13. Known hypersensitivity to fosmanogepix, manogepix, caspofungin, any echinocandin, fluconazole or to any of their excipients.
14. 14. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and Sponsor and Sponsor delegate employees directly involved in the conduct of the study and their family members.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with an overall response of treatment success at end of study treatment (EOST). Time Frame: EOST (up to Day 42)

Secondary endpoints 13

1. 1. Proportion of patients alive at Day 30. Time Frame: Day 30
2. 2. Proportion of patients with overall response of treatment success at Day 7. Time Frame: Day 7
3. 3. Proportion of patients with an overall response of treatment success at Day 14. Time Frame: Day 14
4. 4. Proportion of patients with an overall response of treatment success at end of IV treatment (EOIV). Time Frame: up to Day 42
5. 5. Proportion of patients with an overall response of treatment success (sustained) at follow-up 6 weeks after EOST. Time Frame: approximately up to 12,5 weeks
6. 6. Proportion of patients with clinical response of success at Day 7, Day 14, EOIV, EOST, Follow-up 6- weeks after EOST. Time Frame: Day 14, EOIV (up to Day 42), EOST (up to Day 42), Follow-up 6-weeks after EOST
7. 7. Proportion of patients with mycological response of eradication or presumed eradication at Day 7, Day 14, EOIV, EOST, Follow-up 6-weeks after EOST. Time Frame: Day 14, EOIV (up to Day 42), EOST (up to Day 42), Follow-up 6-weeks after EOST
8. 8. Time to first negative blood culture in patients on fosmanogepix compared to caspofungin/fluconazole. Time Frame: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
9. 9. Incidence of treatment-emergent adverse event (TEAEs), serious adverse events (SAEs), treatment-related adverse events (AEs), adverse events of special interest (AESI)and AEs leading to discontinuation. Time Frame: Screening up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
10. 10. Number of patients with clinically significant laboratory abnormalities. Time Frame: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
11. 11. Number of patients with abnormal neurological examination findings. Time Frame: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
12. 12. Assessment of 12-lead electrocardiogram (ECGs). Time Frame: Baseline up to follow-up 6-weeks after EOST (approximately up to 12,5 weeks)
13. 13. Plasma concentrations versus time of fosmanogepix (prodrug) and manogepix (active moiety). Time Frame: Day 3: 0, 3, 6, 9 and 24 hours post-dose; Day 7, 14, 21, 28, 35; EOST: 72 and 192 hours post-dose

Investigational products

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

Test 2

Comparator 2

Placebo 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Basilea Pharmaceutica International AG Allschwil

Sponsor organisation

Basilea Pharmaceutica International AG Allschwil

Address

Hegenheimermattweg 167b

City

Allschwil

Postcode

4123

Country

Switzerland

Scientific contact point

Organisation

Basilea Pharmaceutica International AG Allschwil

Contact name

Clinical Medical Lead

Public contact point

Organisation

Basilea Pharmaceutica International AG Allschwil

Contact name

Clinical Medical Lead

Third parties 7

Locations

8 EU/EEA countries · 49 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

Documents 54 files

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

Application history

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