A Study of the Dosing, Efficacy, and Safety of Oral Cysteamine in Adult Patients With Cystic Fibrosis Exacerbations (CARE-CF1)

NovaBiotics

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: Placebo Oral Capsule; Drug: Cysteamine

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT03000348

NBTCS02

Details and patient eligibility

About

This study investigates the use of cysteamine in the treatment of adults with Cystic Fibrosis who are experiencing an exacerbation of CF-associated lung disease. There are six different potential dosing regimens, including one that is placebo.

Full description

This is a multicenter, double-blind, randomized, placebo-controlled, 6-arm study to investigate the optimal dose regimen, efficacy, and safety of cysteamine in the treatment of adult patients with CF who are experiencing an exacerbation of CF-associated lung disease. Patients will be screened for the study and eligible patients will be randomized to receive either cysteamine or placebo as add-on therapy to their standard of care treatment for CF-associated lung disease.

Enrollment: 91 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. CF-associated lung disease with documented history of chronic infection with Gram-negative organism(s)

2. Established patient of the Principal Investigator's CF Multi Disciplinary Team (MDT)

3. Age ≥18 years

4. Weight >40 kg

5. FEV1 >30% of predicted within the 6 months prior to study exacerbation

6. At the baseline visit: experiencing a new exacerbation of CF-associated lung disease (based on Investigator assessment of ≥4 symptoms present on the Fuchs' criteria) requiring treatment that includes an aminoglycoside antibiotic

7. Females of childbearing potential will be included if they are either sexually inactive (sexually abstinent for 14 days prior to the first study drug dose continuing through 28 days after the last study drug dose, or using one of the following highly effective contraceptive (i.e. results in <1% failure rate when used consistently and correctly) methods in this trial:

   1. intrauterine device (IUD);
   2. surgical sterilization of the partner (vasectomy for 6 months minimum);
   3. combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal);
   4. progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable);
   5. intrauterine hormone releasing system (IUS);
   6. bilateral tubal occlusion.

8. Females of childbearing potential agree to remain sexually inactive or to keep the same birth control method for at least 28 days following the last dose.

9. A female of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first study drug dose:

   1. hysteroscopic sterilization;
   2. bilateral tubal ligation or bilateral salpingectomy;
   3. hysterectomy;
   4. bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to the first study drug dose and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status.

10. A non-vasectomized male subject agrees to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study medication and the female partner agrees to comply with inclusion 7 or 9. For a vasectomized male who has had his vasectomy 6 months or more prior to study start, it is required that they use a condom during sexual intercourse. A male who has been vasectomized less than 6 months prior to study start must follow the same restrictions as a non-vasectomized male.

11. If male, agrees not to donate sperm from the first study drug dose until 90 days after dosing.

12. Willing and able to comply with all protocol requirements and procedures, including induction of sputum, if necessary

13. Willing and able to provide signed and dated informed consent

Exclusion criteria

1. Hypersensitive to cysteamine or to any of the excipients
2. Hypersensitive to penicillamine
3. Transplant recipient
4. Participation in any other interventional clinical research study (participation in observational studies is not exclusionary) within 30 days of Baseline (Day 0), and any planned participation in an interventional clinical research study for the duration of this study
5. If female, pregnancy, planned pregnancy, or breast-feeding
6. Any other significant disease/disorder which, in the Investigator's opinion, either puts the patient at risk due to study participation, or may influence the results of the study or the patient's ability to participate in the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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91 participants in 6 patient groups, including a placebo group

High Dose, Once per day

Active Comparator group

Description:

Patient takes one oral dose of Cysteamine (high dose) per day, in the morning. The patient takes two oral placebo doses, one at mid-day and one in the evening.

Treatment:

Drug: Cysteamine

Drug: Placebo Oral Capsule

High Dose, Twice per day

Active Comparator group

Description:

Patient takes two oral doses of Cysteamine (high dose) per day, one in the morning and one in the evening. The patient takes one oral placebo dose, at mid-day.

Treatment:

Drug: Cysteamine

Drug: Placebo Oral Capsule

High Dose, Three times per day

Active Comparator group

Description:

Patient takes three oral doses of Cysteamine (high dose) per day, one in the morning, one at mid-day and one in the evening.

Treatment:

Drug: Cysteamine

Placebo

Placebo Comparator group

Description:

Patient takes three oral doses of placebo, one in the morning, one at mid-day and one in the evening.

Treatment:

Drug: Placebo Oral Capsule

Low Dose, Three times per day

Active Comparator group

Description:

Patient takes three oral doses of Cysteamine (low dose) per day, one in the morning, one at mid-day and one in the evening.

Treatment:

Drug: Cysteamine

Drug: Placebo Oral Capsule

Mid-Range Dose, Three times per day

Active Comparator group

Description:

Patient takes three oral doses of Cysteamine (mid-range dose) per day, one in the morning, one at mid-day and one in the evening.

Treatment:

Drug: Cysteamine

Drug: Placebo Oral Capsule