Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults (APPLAUD)

Laurent Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: LAU-7b; Drug: Placebo oral capsule

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03265288

LAU-14-01

Details and patient eligibility

About

An International Phase II, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of LAU-7b administered once-daily for 6 months for the treatment of CF.

Full description

An International Phase II, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of LAU-7b administered once-daily for 6 months for the treatment of CF. All patients will remain on their CF standard-of-care treatments over the trial duration.

The goal for the treatment with LAU-7b in CF is to preserve lung function by reducing the persistent inflammation in the lung and to improve its capacity to defend against resistant bacteria such as Pseudomonas aeruginosa.

The treatment regimen will consist of 6 consecutive "dosing cycles" of 21 days each, spaced by study drug-free periods of 7 days. A total of 136 eligible adult patients with CF will be randomized to receive 300 mg LAU-7b or placebo in a 1:1 ratio. The participation in the study will last about 7 months.

Enrollment: 166 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Screening FEV1 between 40% and 100% predicted value for age, gender and height, in patients capable of properly performing the test;
• History of pulmonary exacerbation, defined as at least one (1) pulmonary exacerbation in the year prior to Screening which resulted in documented intravenous or Oral antibiotics;
• Patients are eligible independently of their history of pulmonary Pseudomonas aeruginosa (PsA) infection and their PsA status at screening;
• If taking Kalydeco® (ivacaftor), Orkambi® (ivacaftor/lumacaftor), Symdeko® (ivacaftor/tezacaftor) or other commercially available CFTR modulator products, patients must be taking it for a minimum of 3 months prior to screening if naïve to CFTR modulators and 1 month if switched from another CFTR modulator product and deemed to tolerate it;
• No change in CF and allowed systemic chronic therapy for a minimum of 5 weeks prior to randomization, of which 2 weeks minimum are prior to screening;
• Female patients of child bearing potential should be on highly effective contraceptive methods during the study;
• Male patients with spouse or partner of child bearing potential, or pregnant, are eligible if they use an appropriate method of contraception.

Exclusion criteria

• Pregnancy: due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible;
• Breast milk feeding by study patient is NOT allowed;
• Clinically abnormal renal function: serum creatinine > 132 μM (1.5 mg/dL);
• Clinically abnormal liver function: Total bilirubin >1.5 x ULN (in the absence of demonstrated Gilbert's syndrome), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2.5 x ULN;
• Patients with plasma retinol levels below 0.7 µM;
• Presence of nyctalopia or hemeralopia at enrolment, or any other serious retinal, ophthalmological condition;
• Presence of serious dermatological conditions at entry, including inflammatory or xerotic skin pathologies such as psoriasis or ichthyosis;
• Intake of chronic systemic steroids in the month prior to screening and during the study;
• History of acute infections (viral/bacterial/fungal) within 5 weeks prior to randomization, of which 2 weeks minimum are prior to screening, whether or not treated and resolved;
• Presence of infection with Burkholderia cepacia (including all species within the Burkholderia cepacia complex group, and Burkholderia gladioli) in the 12 months prior to screening;
• Patients with a confirmed diagnosis (as per the Cystic Fibrosis Foundation diagnostic criteria) of Allergic BronchoPulmonary Aspergillosis (ABPA) and actively being treated with corticosteroids and/or anti fungal agents.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

166 participants in 2 patient groups, including a placebo group

LAU-7b

Experimental group

Description:

Active drug fenretinide (as LAU-7b capsules)

Treatment:

Drug: LAU-7b

Placebo

Placebo Comparator group

Description:

Placebo oral capsule (as inactive capsules identical to active arm)

Treatment:

Drug: Placebo oral capsule