Study to Evaluate the Safety & Tolerability of MRT5005 Administered by Nebulization in Adults With Cystic Fibrosis (RESTORE-CF)

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Status and phase: Unknown; Phase 2; Phase 1

Conditions: Cystic Fibrosis

Treatments: Drug: Normal saline; Drug: MRT5005

Study type: Interventional

Funder types: Industry

Identifiers

NCT03375047

MRT5005-101

Details and patient eligibility

About

This Phase 1/2, first-in-human study will evaluate the safety and tolerability of single and multiple escalating doses of MRT5005 administered by nebulization to the respiratory tract of adult subjects with CF.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed diagnosis of CF as defined by both of the following:

  • Two CF disease-causing CFTR mutations in Class I or II (genotype confirmed at the screening visit).
  • Chronic sinopulmonary disease and/or gastrointestinal/nutritional abnormalities consistent with CF disease.

• Clinically stable CF disease, as judged by the investigator.

• FEV1 ≥50% and ≤90% of the predicted normal for age, gender, and height at screening.

• Resting oxygen saturation ≥92% on room air (pulse oximetry).

Exclusion criteria

• An acute upper or lower respiratory infection, pulmonary exacerbation, clinically significant episode of hemoptysis or change in chronic respiratory medications (including antibiotics) for CF lung disease within 28 days prior to dosing with investigational product on Day 1.
• Receiving treatment with ivacaftor monotherapy (KALYDECO)
• For all groups except Daily dosing: Receiving treatment with triple combination therapy (TRIKAFTA).
• Subjects with a Class III, IV, or V CFTR gene mutation in at least 1 allele.
• Infection with highly virulent bacteria associated with accelerated decline in pulmonary function and/or decreased survival (e.g., Burkholderia cenocepacia, Burkholderia dolosa, Mycobacterium abscessus).

Treatment with ORKAMBI or SYMDEKO is not an exclusion for this study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 7 patient groups, including a placebo group

Low Dose

Experimental group

Description:

8 mg MRT5005

Treatment:

Drug: MRT5005

Low/Mid Dose

Experimental group

Description:

12 mg MRT5005

Treatment:

Drug: MRT5005

Mid Dose

Experimental group

Description:

16 mg MRT5005

Treatment:

Drug: MRT5005

Mid/High Dose

Experimental group

Description:

20 mg MRT5005

Treatment:

Drug: MRT5005

High Dose

Experimental group

Description:

24 mg MRT5005

Treatment:

Drug: MRT5005

Placebo Comparator

Placebo Comparator group

Description:

Normal Saline 0.9% USP

Treatment:

Drug: Normal saline

Daily Dose

Experimental group

Description:

20 mg MRT5005 delivered in 5 consecutive daily doses of 4mg

Treatment:

Drug: MRT5005