A Phase 3 Clinical Trial of Intravenous Sodium Thiosulfate in Acute Calciphylaxis Patients

NCT03150420 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: ST-001
• Study Type: interventional
• Target: 29
• Locations: 3 countries
• Sites: 21

Brief Summary

This multicenter, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of intravenous Sodium Thiosulfate Injection for treatment of acute calciphylaxis-associated pain in chronic hemodialysis patients.

Conditions

Calciphylaxis

Keywords

calciphylaxis; calcific uremic arteriolopathy, calcinosis; calcium metabolism disorders; metabolic diseases; sodium thiosulfate

Outcome Measures

Primary Outcomes (1)

• Number of patients with 30% improvement in pain severity

  To compare the effects of treatment with intravenous Sodium Thiosulfate Injection vs. placebo for the proportion of patients (responders) who achieve a ≥ 30% reduction based upon pain intensity score (modified BPI/SF).

  randomization to 3 weeks

Secondary Outcomes (4)

• Secondary Endpoint-a: Number of patients with stabilization or improvement in calciphylaxis skin lesions.

  randomization to 3 weeks

• Secondary Endpoint-b: Occurence of surgical debridement of skin lesions and/or amputation.

  during week 3

• Secondary Endpoint-c: Occurrence of surgical debridement of skin lesions and/or amputation.

  randomization to 3 weeks

• Secondary Endpoint-d: Time to achieve ≥ 30% improvement in pain severity

  randomization to 3 weeks

Study Arms (2)

Sodium Thiosulfate

EXPERIMENTAL

Sodium Thiosulfate Injection (25 grams sodium thiosulfate)

Drug: Sodium Thiosulfate

Placebo-Normal Saline

PLACEBO COMPARATOR

0.9% sodium chloride injection, USP (normal saline)

Drug: Placebo-Normal Saline

Interventions

Sodium Thiosulfate DRUG

Intravenous Sodium Thiosulfate Injection (25 grams sodium thiosulfate) to be administered each hemodialysis session (3 times weekly) for 3 weeks

Also known as: Intravenous Sodium Thiosulfate Injection

Sodium Thiosulfate

Placebo-Normal Saline DRUG

Placebo: to be administered each hemodialysis session (3 times weekly) for 3 weeks

Also known as: 0.9% sodium chloride solution

Placebo-Normal Saline

Eligibility Criteria

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

You may qualify if:

• Informed of the investigational nature of the study and sign written informed consent
• Willing and able to adhere to all study-related procedures, including adherence to study medication regimen
• Male or female ≥18 years old
• End-stage renal disease on chronic hemodialysis
• Calciphylaxis with active skin lesion(s) of any morphological appearance (including but not limited to livedo, induration, ulceration, etc.) and tissue histology review consistent with calciphylaxis diagnosis. Histological features consistent with calciphylaxis will include soft tissue calcification, microthrombosis, and/or fibrointimal hyperplasia of dermal arterioles
• Acute pain associated with calciphylaxis lesions pain intensity score of ≥ 5 at initial screening on the modified BPI/SF scale
• Women of childbearing potential must have a pregnancy test (urine or serum \[if anuric\]) at screening and not be pregnant and willing to use an acceptable method of contraception for the entire duration of the study (3 weeks)

You may not qualify if:

• Peritoneal dialysis patients
• Current congestive heart failure exacerbation
• Baseline abnormalities related to QT prolongation (corrected QT interval \> 470 ms), hypocalcemia (serum albumin-corrected calcium \< 8 mg/dL ), metabolic acidosis (serum bicarbonate \< 18 mmol/L, hypotension (resting systolic blood pressure while seated \< 80), or interdialytic weight gain ≥ 4.0 kg
• History of ventricular arrhythmias including ventricular fibrillation or ventricular tachycardia associated with shortness of breath, dizziness, hypotension, or syncope
• Any prior (within the past 30 days) or current intravenous Sodium Thiosulfate Injection treatment
• Other investigational agent (drug, biologic, or device) study within the past 30 days and/or for the duration of the trial
• Pregnant or lactating women
• Significant other acute or chronic concomitant diseases (including but not limited to hepatic, cardiovascular, pulmonary, or oncologic disease, sepsis, pulmonary edema, pulmonary embolism) that would be inconsistent with survival for at least 3 months
• Other serious concurrent or recent medical or psychiatric condition which, in the opinion of the Investigator, makes the patient unsuitable for participation in this study
• Ongoing application of dialysate admixed with iron salt e.g. ferric pyrophosphate during the entire trial period (patients who are on dialysate admixed with iron salt at screening are eligible if dialysate admixed with iron salt can be substituted with non-iron based dialysate and patients can be maintained on non-iron based dialysate therapy for the entire duration of trial period)
• Recent (within 1 week) history of surgical parathyroidectomy or scheduled for surgical parathyroidectomy during the course of the study
• History of opioid addiction

Sponsors & Collaborators

• Hope Pharmaceuticals: lead

Study Sites (21)

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Northwestern University Hospital

Chicago, Illinois, 60611, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Veterans Administration Medical Center

Albany, New York, 12208, United States

Location

The Icahn School of Medicine at Mount Sinai Hospital

New York, New York, 10029, United States

Location

Sanford Health

Fargo, North Dakota, 58122, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02914, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Veterans Administration Medical Center

Salem, Virginia, 24153, United States

Location

University of Calgary Foothills Medical Center

Calgary, Alberta, T2W 1S7, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 1Z1, Canada

Location

Health Sciences Centre Winnipeg

Winnipeg, Manitoba, R2V 3M3, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 0A9, Canada

Location

Salford Royal Hospital NHS Foundation Trust

Salford, Manchester, M6 8HD, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Lister Hospital

Stevenage, SG1 4AB, United Kingdom

Location

MeSH Terms

Conditions

Calciphylaxis; Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases

Interventions

sodium thiosulfate; Sodium Chloride

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Craig Sherman, MD

  Hope Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: May 12, 2017
• Study Start: May 24, 2017
• Primary Completion: April 15, 2020
• Study Completion: April 15, 2020
• Last Updated: May 19, 2020

Record last verified: 2020-05

Locations

US (12); CA (5); GB (4)