The RJVA-001 First in Human Trial in Adults with Inadequately Controlled Type 2 Diabetes.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fractyl Health Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2026-04-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fractyl Health

External identifiers

EU CT number

2025-524438-24-00

WHO UTN

U1111-1331-8762

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Efficacy, Safety, Pharmacokinetic

To evaluate the safety and tolerability of RJVA-001.

Secondary objectives 5

1. 1. To evaluate preliminary efficacy of RJVA-001 treatment in reducing hyperglycemia.
2. 2. To characterize the immune response to RJVA-001 capsid and transgene.
3. 3. To characterize the viral shedding of adeno-associated virus serotype 9 (AAV9) after RJVA-001 therapy.
4. 4. To evaluate the effect of RJVA-001 on other continuous glucose monitoring parameters.
5. 5. To evaluate the effect of RJVA-001 on hepatic parameters.

Conditions and MedDRA coding

Type 2 Diabetes

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1. Signed and dated written informed consent in accordance with Good Clinical Practice and local legislation.
2. 2. Age 35 to 70 years (inclusive).
3. 3. Agree to use appropriate form of contaception for the study duration and for at least 1 year after RJVA-001 infusion.
4. 4. Diagnosis of Type 2 Diabetes.
5. 5. Body mass index as indicated in the study protocol.
6. 6. Fasting plasma glucose and hemoglobin A1c levels as stated in the study protocol.
7. 7. Participants are taking glucagon-like peptide-1 receptor agonists (GLP-1RA) at the maximum tolerated maintenance dose and taking permitted non-insulin glucose lowering agents other than GLP-1RA.
8. 8. Random C-peptide level as stated in the study protocol.
9. 9. Normal thyroid function as defined in the study protocol.
10. 10. Normal calcitonin level as stated in the study protocol.
11. 11. Based on Investigator’s judgement, continuous dose escalation or modification of participant’s current treatment regimen is deemed unacceptable.
12. 12. Participant has deferred insulin therapy.
13. 13. Able to tolerate a once-weekly injectable, once-daily injectable or oral GLP-1RA treatment as evidenced by ongoing treatment and benefit from GLP-1RAs at an efficacious dose.
14. 14. Participants must be willing to abstain from semen/blood donation through 1 year after RJVA-001 injection.
15. 15. Participants must be willing to abstain from alcohol use until completion of the sirolimus taper.
16. 16. Participants must agree not to initiate any new or intensive diet or exercise regimens and/or any new weight loss medications during study participation.

Exclusion criteria 31

1. 1. Diagnosis of Type 1 diabetes or history of ketoacidosis, monogenic diabetes or latent autoimmune diabetes of adults or presence of 1 or more islet cell autoantibodies.
2. 10. General contraindications to deep or conscious sedation or general anesthesia or high risk as determined by anesthesiologist.
3. 11. Contraindications to upper gastrointestinal (GI) endoscopy.
4. 12. History of tuberculosis.
5. 13. Immunization with live vaccines within 30 days prior to screening, Visit 1.
6. 14. Known hypersensitivity or allergy to eggs, milk, wheat, or [13C]-labeled Spirulina substrates.
7. 15. Any contraindications to the infusate to be delivered.
8. 16. History of hepatic decompensation/acute liver disease, acute or chronic active hepatitis B or C, alcoholic or autoimmune chronic hepatitis as stated in the study protocol. Known portal hypertension.
9. 17. History of symptomatic heart failure with reduced or preserved ejection fraction.
10. 18. History of clinically significant valvular heart disease or severe aortic stenosis.
11. 19. Acute coronary syndrome, stroke or transient ischemic attack as stated in the study protocol.
12. 2. History of dose-limiting persistent adverse side effects from GLP-1RA use.
13. 20. History of severe peripheral vascular disease.
14. 21. History of active malignancy or partial remission from clinically significant malignancy, personal or familial history of medullary thyroid carcinoma as stated in the study protocol.
15. 22. Suspected GI malignancy.
16. 23. History of blood dyscrasias or any disorders causing hemolysis or unstable erythrocytes.
17. 24. History of alcohol or illicit substance abuse as stated in the study protocol.
18. 25. Intake of an investigational drug within 5 half-lives prior to visit 1 or active participation in another clinical trial of an investigational drug or device.
19. 26. Contraindication to systemic steroids or sirolimus.
20. 27. Participant is on a weight loss program and is not in the weight maintenance phase, or is on a GLP-1 weight loss medication.
21. 28. Participant has poorly controlled hypertension as defined in the study protocol.
22. 29. Any other clinical or mental condition which, in the opinion of the Investigator, would jeopardize participant’s safety or makes participant a poor candidate for clinical trial participation.
23. 3. History of non-adherence to diabetes treatment in the previous 6 months, as determined by the Investigator.
24. 30. Laboratory and Radiographic Exclusions as stated in the study protocol.
25. 4. Known history of diabetic retinopathy.
26. 5. Active systemic infection or undergoing treatment for recent infection. Does not apply to completely treated infection.
27. 6. Condition(s) requiring systemic immunomodulation or whose immune status makes the participant a poor candidate for clinical trial participation.
28. 7. History of chronic or acute pancreatitis, or elevated fasting triglycerides as stated in the study protocol.
29. 8. Family history of hemochromatosis or cystic fibrosis, as self-reported by the participants will be documented.
30. 9. Symptomatic cholelithiasis or cholecystitis unless treated by cholecystectomy.
31. 31. Concomitant Medication Exclusions as stated in the study protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence, severity, dose-relationship of Adverse Events and changes in laboratory evaluations.

Secondary endpoints 4

1. 1. Change in transgene secretion and glycemic parameters.
2. 2. Anti-AAV9 antibody titers, anti-GLP-1 antibody titers and enzyme-linked immunosorbent spot for AAV9 and GLP-1.
3. 3. Digital polymerase chain reaction for AAV9 in samples.
4. 4. Change from Baseline parameters using continuous glucose monitoring.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fractyl Health Inc.

Sponsor organisation

Fractyl Health Inc.

Address

3 Van De Graaff Drive Suite 200

City

Burlington

Postcode

01803-5136

Country

United States

Scientific contact point

Organisation

Fractyl Health Inc.

Contact name

Fractyl Health

Public contact point

Organisation

Fractyl Health Inc.

Contact name

Fractyl Health

Third parties 8

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 9 files

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

Application history

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