A Phase 1/2, Multicenter Study Evaluating the Safety, Tolerability, and Biodistribution of RCT2100 with Single-Ascending Doses in Healthy Participants and Multiple-Ascending Doses and Proof-of-Concept in Participants with Cystic Fibrosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Recode Therapeutics Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

28 Aug 2024 → ongoing

Decision date (initial)

2024-07-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ReCode Therapeutics, Inc.

External identifiers

EU CT number

2024-512169-15-00

ClinicalTrials.gov

NCT06237335

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Therapy

To assess the safety and tolerability of multiple-ascending doses of inhaled RCT2100 administered via nebulizer to participants with CF

Secondary objectives 5

1. To characterize the biodistribution of multiple-ascending doses of components of RCT2100
2. To evaluate the effect of RCT2100 on pulmonary function in participants with CF
3. To determine the effect of RCT2100 on disease-specific QOL instrument
4. To characterize the potential for development of ADAs against CFTR protein following multiple inhaled doses of RCT2100
5. To select a dose for Part 3 and Part 4 of the study

Conditions and MedDRA coding

Cystic Fibrosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Males or females aged 18 to 60 years, inclusive, on the date of informed consent
2. Confirmed diagnosis of CF
3. a) Not eligible for CFTR modulators based on having mutations of CFTR gene on both alleles that are not responsive to CFTR modulator therapy OR b) Eligible for CFTR modulators (based on local prescribing information) but not using CFTR modulators due to intolerance or contraindications
4. Forced expiratory volume in 1 second ≥50% and ≤100% of predicted mean value for age, sex, and height (equations of the Global Lung Function Initiative [GLI]) at the Screening Visit. Spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria for acceptability and repeatability
5. Please refer to the protocol for details

Exclusion criteria 8

1. Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
2. An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for sinopulmonary disease within 4 weeks before the first dose of study drug (Day 1)
3. Lung infection with organisms associated with a more rapid decline in pulmonary status (including, but not limited to, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). For participants who have had a history of a positive culture, the Investigator will apply the following criteria to establish whether the participant is free of infection from such organisms: • The participant has not had a respiratory tract culture positive for these organisms within the 12 months before the date of informed consent • The participant has had at least two respiratory tract cultures negative for such organisms within the 12 months before the date of informed consent, with the first and last of these separated by at least 3 months, and the most recent one within the 6 months before the date of informed consent
4. Arterial oxygen saturation on room air less than 94% at screening
5. Estimated glomerular filtration rate < 30 mL/minute/1.73 m2 calculated with the Chronic Kidney Disease Epidemiology Collaboration formula
6. Treatment with a CFTR modulator (Eg. Kalydeco, Trikafta, Symdeko, Orkambi, Alyftrek) within 12 weeks of Screening
7. History of poorly controlled diabetes
8. Please refer to the protocol for details.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability as assessed by number of participants with AEs and SAEs

Secondary endpoints 6

1. Biodistribution parameters may be derived from concentrations of RCT2100 components in blood (where feasible). Parameters may include but are not limited to the following: AUC, Cmax, Tmax, and t1/2
2. Absolute change in percent predicted FEV1 (ppFEV1) from baseline to Week 4 (escalation cohorts 1 to 3) or Week 12 (expansion cohort)
3. Change from baseline in CF questionnaire-revised (CFQ-R) respiratory domain score through Week 4 (escalation cohorts 1 to 3) or Week 12 (expansion cohort)
4. Incidence and titer of anti-CFTR binding antibodies
5. Based on safety and tolerability at projected efficacious doses
6. Please refer to the protocol for details.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Recode Therapeutics Inc.

Sponsor organisation

Recode Therapeutics Inc.

Address

1140 Obrien Drive

City

Menlo Park

Postcode

94025-1411

Country

United States

Scientific contact point

Organisation

Recode Therapeutics Inc.

Contact name

Clinical Development

Public contact point

Organisation

Recode Therapeutics Inc.

Contact name

Clinical Development

Third parties 14

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 28 files

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

Application history

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