Bucillamine Phase 2 Trial in Patients With Cystinuria

NCT02942420 | Unknown Phase 2 FDA Drug

• 1 other identifier: REV401
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

Subjects on a standard regimen of tiopronin (cystine binding thiol drug; CBTD) plus prescribed first-line therapy (i.e. on a hydration, alkali therapy and dietary restriction) who are failing therapy will be selected for this trial. After completing informed consent, the subject will have Screening consisting of medication history and physical examination with vital signs. Samples of blood and urine will be taken for clinical laboratory and urinalysis. Patients will undergo a 12-lead ECG test. A history of side effects with current CBTD as well as laboratory recordings of abnormalities attributable to treatment will also be recorded. Subjects will be dosed in a sequential manner, starting with the low dose group (300 mg/day), then proceeding to the 600 mg.day dose group.. Safety and tolerability will be monitored closely by an Independent Medical Monitor (IMM) and based on the IMM's assessment that it is safe to proceed to the higher dose (600 mg/day), subsequent subjects will be enrolled into that group. Up to 15 subjects each will be enrolled into either Group A or Group B. After 7 days on the assigned bucillamine dose, a 24-hour urine sample will be taken and after completing the Day 8 safety visit, subjects will undergo a 7 day washout where no CBTDs will be taken. Thereafter, subjects will be allowed to resume their originally prescribed CBTDs under Investigator's supervision. One week following study drug discontinuation, subjects will return to the clinic for follow-up safety assessments.

Conditions

Cystinuria

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Number, type, and severity of AEs observed by the staff during visits on Days 0 (dosing), 3, 8 and +1 week post-study or volunteered by the subject during telephone follow-up on Days 2 and 7.

  Days 0, 2, 3, 7, 8 and + 1 wk post study

Secondary Outcomes (2)

• Cystine Excretion

  Day 0 and Day 8

• Cystine Capacity

  Day 0 and Day 8

Study Arms (2)

Dose Group A

EXPERIMENTAL

Bucillamine 300 mg/day

Drug: Bucillamine

Dose Group B

EXPERIMENTAL

Bucillamine 600 mg/day

Drug: Bucillamine

Interventions

Bucillamine DRUG

Thiol donor which results in a cysteine-bucillamine complex for removing excess cysteine from the urine

Dose Group A; Dose Group B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects of any gender and of any race ≥18 and ≤80 years of age
• Subjects with proven cystinuria who are failing their standard drug therapy of tiopronin plus first-line therapy (hydration, alkali and diet restriction) and who meet the following criteria.
• formed new stones while taking a thiol.
• had increase in stone size of pre-existing stones while taking a thiol.
• had a urologic intervention for stones while taking a thiol
• Subjects must be able to reliably urinate in a collection vessel and measure urine volume
• Subjects must have documentation of a stable complete blood count (CBC) and urinalysis (UA) in the 6 months prior to date of enrollment
• Subjects may have a history of but not currently active CNS disorders or symptoms/effects (e.g., headache)
• Subjects must have adequate organ function, evidenced by the following laboratory results within 30 days prior to enrollment:
• Absolute neutrophil count \>2000 cells/mm
• Platelet count \>140,000 cells/mm3
• Hemoglobin \>11.0 g/dl
• Albumin ≥2.5 g/dl
• Total bilirubin ≤1.5 upper limit of normal (ULN)
• SGOT (aspartate aminotransferase \[AST\]), SGPT (alanine aminotransferase \[ALT\]), and alkaline phosphatase (ALP)

You may not qualify if:

• Subjects with renal colic
• Subjects who are scheduled to undergo a surgical procedure
• Subjects on D-penicillamine (see page 35 for explanation)
• Subjects with cancer
• Subjects with acute or chronic infections including HIV, tuberculosis, hepatitis B or hepatitis C
• Patients with proteinuria ≥30 mg that is confirmed on repeat laboratory assessment within 24 hours
• Subjects with QTc interval \>450 ms
• A history of, hypokalemia and family history of Long QT syndrome
• Use of concomitant medications that may prolong QT/QTc interval
• Patients with significant heart failure and activity impairment (Class III-IV of the New York Heart Association (NYHA)
• Subjects with serious hepatic disorder (Child-Pugh scores B or C)
• Subjects with a history of alcohol or substance abuse within the 12 months prior to enrollment
• Subjects with history of or active blood dyscrasia such as myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia.
• Subjects with Coagulopathy (regardless if controlled by pharmacotherapy or not)
• Subjects who have any concomitant illness (including active significant infection) or other finding that, in the opinion of the Investigator, would confound the study data or place the subject at unacceptable risk if the subject were to participate in the study, or that would require frequent adjustments in concomitant medications during the course of the study

Sponsors & Collaborators

• Revive Therapeutics, Ltd.: lead

Study Sites (5)

University of Alabama - Department of Urology

Birmingham, Alabama, 35294, United States

RECRUITING

Massachusette General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

New York University School of Medicine

New York, New York, 10016, United States

RECRUITING

Omega Medical Research

Warwick, Rhode Island, 02886, United States

RECRUITING

University of Wisconsin School of Medicane and Public Health

Madison, Wisconsin, 53705,, United States

RECRUITING

MeSH Terms

Conditions

Cystinuria

Interventions

bucillamine

Condition Hierarchy (Ancestors)

Renal Aminoacidurias; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Fabio Chianelli

CONTACT

905-605-5535; fabio@revivethera.com

Angela Fuda

CONTACT

905-605-5535; angela@revivethera.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: The study is unmasked, i.e., is open label.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dosing will occur sequentially from low to high dose: The 600 mg bucillamine dose group (Arm A) will enroll first, then after safety is assured, the 900 mg bucillamine dose group will enroll.

Study Record Dates

• First Submitted: October 19, 2016
• First Posted: October 24, 2016
• Study Start: May 1, 2017
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: May 18, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)