A Study of LJPC-401 for the Treatment of Iron Overload in Adult Patients With Hereditary Hemochromatosis

• ClinicalTrials.gov Identifier: NCT03395704
• Recruitment Status: Completed
• First Posted: January 10, 2018
• Last Update Posted: March 4, 2020
• Sponsor: La Jolla Pharmaceutical Company
• Collaborator: PRA Health Sciences
• Information provided by (Responsible Party): La Jolla Pharmaceutical Company

Study Description

Brief Summary:

This study is a Phase 2 multicenter, randomized, placebo controlled, single-blind study. The primary objective of the study is to compare the effect of weekly dosing of LJPC-401 (synthetic human hepcidin) versus placebo on transferrin saturation (TSAT) in an adult hereditary hemochromatosis patient population.

Condition or disease	Intervention/treatment	Phase
Hereditary Hemochromatosis	Drug: LJPC-401; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multi-Center, Randomized, Placebo Controlled, Single-Blind Study With LJPC-401 for the Treatment of Iron Overload in Adult Patients With Hereditary Hemochromatosis
• Actual Study Start Date: November 29, 2017
• Actual Primary Completion Date: October 28, 2019
• Actual Study Completion Date: October 28, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: LJPC-401; LJPC-401 solution for subcutaneous injection only, 5mg/1 mL (5mg/mL) or 10mg/1mL (10mg/mL) single use vial	Drug: LJPC-401; LJPC-401 subcutaneous injection, up to 20 mg weekly for 16 weeks. The minimum weekly dose will be 5 mg and the maximum weekly dose of LJPC-401 will be 20 mg.; Other Name: synthetic human hepcidin
Placebo Comparator: Placebo; 0.9% Sodium Chloride Injection, USP, or equivalent	Drug: Placebo; 0.9% Sodium Chloride Injection, USP, or equivalent; Other Name: Normal saline

Outcome Measures

Primary Outcome Measures :

1. Effect of LJPC-401 versus placebo on blood iron levels [ Time Frame: 16 Weeks ]
   Change in transferrin saturation (TSAT) as measured by blood laboratory tests.

Secondary Outcome Measures :

1. Effect of LJPC-401 versus placebo on incidence of phlebotomy [ Time Frame: 16 Weeks ]
2. Effect of LJPC-401 versus placebo on blood iron levels [ Time Frame: 16 Weeks ]
   Change in serum ferritin as measured by blood laboratory tests
3. Effect of LJPC-401 versus placebo on the incidence of treatment-emergent adverse events [ Time Frame: 20 Weeks ]
4. Effect of LJPC-401 versus placebo on clinical chemistry laboratory parameters [ Time Frame: 20 Weeks ]
   Safety measure for clinical chemistry parameters including serum creatinine, uric acid, alkaline phosphatase, blood urea nitrogen, albumin, bilirubin (total), phosphate, bicarbonate, lactate dehydrogenase, glucose, calcium, magnesium, chloride, sodium, potassium, alanine aminotransferase, aspartate aminotransferase, and total protein will be assessed. In addition, serum pregnancy test will be assessed.
5. Effect of LJPC-401 versus placebo on hematology laboratory parameters [ Time Frame: 20 Weeks ]
   Safety measure for laboratory hematology parameters including platelet count, red blood cell count, absolute white blood cell count, hemoglobin, hematocrit, reticulocyte count, red cell distribution width, mean corpuscular hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin concentration will be assessed.
6. Effect of LJPC-401 versus placebo on blood iron parameters [ Time Frame: 20 Weeks ]
   Exploratory measure of serum iron, serum transferrin, total iron-binding capacity, unsaturation iron-binding capacity will be assessed to evaluate iron parameters.
7. Effect of LJPC-401 versus placebo on endocrine laboratory parameters [ Time Frame: 16 Weeks ]
   Exploratory measure for endocrine laboratory parameters, including thyroid-stimulating hormone, thyroxine (T4), and triiodothyronine (T3) will be assessed to evaluate changes in thyroid function.
8. Effect of LJPC-401 versus placebo on glucose levels [ Time Frame: 16 Weeks ]
   Exploratory measure for change in hemoglobin A1c will be assessed to evaluate blood sugar levels.
9. Effect of LJPC-401 versus placebo on urinalysis laboratory parameters [ Time Frame: 20 Weeks ]
   Safety measure for urinalysis laboratory parameters including specific gravity, bilirubin, glucose, pH, protein, nitrite, blood, ketones will be assessed. In addition, urine pregnancy test will be assessed at Week 1 (Day 1) to reconfirm eligibility predose and at again at Week 20 for additional safety assessment.
10. Effect of LJPC-401 versus placebo on blood pressure [ Time Frame: 20 Weeks ]
    Safety measure for change in blood pressure.
11. Effect of LJPC-401 versus placebo on heart rate [ Time Frame: 20 Weeks ]
    Safety measure for change in heart rate (bpm).
12. Effect of LJPC-401 versus placebo on body weight [ Time Frame: 20 Weeks ]
    Safety measure for change in body weight (kilograms).
13. Effect of LJPC-401 versus placebo on body temperature [ Time Frame: 20 Weeks ]
    Safety measure for change in body temperature (Celsius).
14. Effect of LJPC-401 versus placebo on general health [ Time Frame: 20 Weeks ]
    Safety measure for change in physical examination (by body system).
15. Effect of LJPC-401 versus placebo on electrical activity of the heart [ Time Frame: 20 Weeks ]
    Safety measure for change in the electrical activity of the heart over a period of time using electrodes placed on the skin and recorded by electrocardiogram (ECG).
16. Effect of LJPC-401 versus placebo on its potential to elicit an immune response [ Time Frame: 20 Weeks ]
    Safety measure of blood samples collected to assess the presence of anti-drug antibodies.
17. Effect of LJPC-401 versus placebo on quality of life [ Time Frame: 16 Weeks ]
    Exploratory measure for change in quality of life as measured by the Short Form Health Survey version 2.0 questionnaire. The scale measures physical functioning; role-physical, bodily pain; general health; vitality; social functioning; role-emotional; mental health and reported health transition. The responses vary depending on the question: Range 1-6 (none to very severe); range 1-5 (all of the time to none of the time or definitely true to definitely false); range 1-4 not at all to quite a bit; range 1-3 (yes, limited a lot to no, not limited at all). All scoring will be tallied by a validated central system (Optum) and provided to the sponsor at the end of the study. Scoring will be analyzed as a change from baseline to end of treatment (Week 16).
18. Effect of LJPC-401 versus placebo on quality of life [ Time Frame: 16 Weeks ]
    Exploratory measure for change in quality of life as measured by the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire. The scale ranges from 1-5 (none to extreme in regards to pain and difficulty during day to day activity. Responses will be analyzed as a change from baseline to end of treatment (Week 16).
19. Exploratory measure for change in quality of life [ Time Frame: 16 Weeks ]
    Exploratory measure for change in quality of life as measured by the Modified Dreisler indicies (FIOHA-Functional Index for Hand OsteoArthritis) questionnaire. The scale ranges from 1-4 (Possible without difficulty to impossible in regards to activities that use hand movement. The results are totaled and scores will be analyzed as a change from baseline to end of treatment (Week 16).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients with clinical diagnosis of hereditary hemochromatosis
2. Patients who are prescribed therapeutic phlebotomy for treatment of hereditary hemochromatosis
3. Patients with serum ferritin and TSAT levels above treatment guidelines
4. Female patients of child bearing potential must have a negative pregnancy test and must be using a highly effective method of contraception during participation in the study, and for 30 days after the last dose of study drug
5. Males must be surgically sterile (vasectomy), or using a highly effective method of contraception during participation in the study, and for 30 days after the last dose of study drug
6. Patient must be willing and able to provide written informed consent

Exclusion Criteria:

1. Patients receiving iron chelation therapy within 7 days prior to the first dose of study drug
2. Patients initiating phlebotomy treatments less than 3 months prior to the first dose of study drug
3. Pregnant or lactating women
4. Patients taking an immunosuppressive agent without prior Sponsor approval
5. Patients participating in an unapproved investigational drug or investigational therapeutic device within 30 days of study drug
6. Patients who are unwilling or unable to comply with the study protocol requirements
7. Patients with type 1 or poorly controlled type 2 diabetes
8. Patients with a concomitant disease, disability or condition, including laboratory abnormality and ECG findings, which may interfere with the conduct of the study, or which would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this study, including, but not limited to, clinically significant arrhythmias, alcohol dependency or abuse, drug dependency or abuse, or psychiatric disease

Contacts and Locations

Locations

United States, Arkansas

Investigative Site

North Little Rock, Arkansas, United States, 72117

United States, California

Investigative Site

Los Angeles, California, United States, 90036

Investigative Site

Palo Alto, California, United States, 94305

Investigative Site

Rialto, California, United States, 92377

Investigational Site

San Diego, California, United States, 91942

Investigative Site

San Francisco, California, United States, 94115

United States, Florida

Investigative Site

Jacksonville, Florida, United States, 32204

United States, Indiana

Investigative Site

Indianapolis, Indiana, United States, 46202

United States, Michigan

Investigative Site

Wyoming, Michigan, United States, 49519

United States, Mississippi

Investigative Site

Jackson, Mississippi, United States, 39216

United States, New York

Investigative Site

East Setauket, New York, United States, 11733

Investigative Site

Manhasset, New York, United States, 11030

Investigative Site

New York, New York, United States, 10029

United States, Texas

Investigative Site

Dallas, Texas, United States, 75246

Investigative Site

Fort Worth, Texas, United States, 76104

Investigative Site

Houston, Texas, United States, 77058

Investigative Site

San Antonio, Texas, United States, 78215

United States, Washington

Investigative Site

Seattle, Washington, United States, 98104

Australia, New South Wales

Investigative Site

Liverpool, New South Wales, Australia, 2170

Investigative Site

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Investigative Site

Brisbane, Queensland, Australia, 4120

Investigative Site

Herston, Queensland, Australia, 4029

Australia, Victoria

Investigative Site

Melbourne, Victoria, Australia, 3004

Australia, Western Australia

Investigative Site

Murdoch, Western Australia, Australia, 6150

France

Investigative Site

Bondy, France, 93140

Investigative Site

Orléans, France, 45000

Investigative Site

Pessac, France, 33604

Investigative Site

Rennes Cedex 9, France, 35033

United Kingdom

Investigative Site

Bradford, England, United Kingdom, BD9 6RJ

Investigative Site

Newcastle Upon Tyne, England, United Kingdom, NE7 7DN

Investigative Site

Portsmouth, England, United Kingdom, PO6 3LY

Sponsors and Collaborators

La Jolla Pharmaceutical Company

PRA Health Sciences

More Information

• Responsible Party: La Jolla Pharmaceutical Company
• ClinicalTrials.gov Identifier: NCT03395704
• Other Study ID Numbers: LJ401-HH01
• First Posted: January 10, 2018
• Last Update Posted: March 4, 2020
• Last Verified: March 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hemochromatosis; Iron Overload; Iron Metabolism Disorders; Metabolic Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Hepcidins; Anti-Infective Agents