NI-0501 is a new drug being tested as first-line treatment for a fatal childhood disease known as hemophagocytic lymphohistiocytosis (HLH). On March 16, 2015, Novimmune SA, the Swiss biopharmaceutical company behind the drug, announced a protocol amendment to their international clinical trial.

Patients diagnosed with hemphophagocytic lymphohistiocytosis (HLH), and who are participating in the company’s ongoing clinical trial of its NI-0501 monoclonal antibody, will now be able to be treated with the drug without having to first fail conventional treatments.

The company recently filed a protocol amendment with the US Food and Drug Administration as well as European regulatory authorities in order to allow first-line treatment in the study. Based on available preliminary data from HLH patients treated with NI-0501 after having failed conventional therapies, regulatory authorities and the Ethical Committees having already completed the review process allowed the proposed amendment to proceed with no change.

The amended protocol has since been implemented at the HLH Center of Excellence at Cincinnati Children’s Hospital, Texas Children’s Hospital, Alfred I. DuPont Hospital for Children and some participating hospitals in Europe. It is expected that all designated study sites will be authorized to implement the amended study protocol within the next several weeks.

“I am extremely pleased that, from now on, critically ill children at any stage of the disease, will have the opportunity to receive a targeted therapy which, because of its mechanism of action, does not cause the toxicities associated with the use of conventional HLH therapies” said Cristina de Min, MD, Chief Medical Officer at Novimmune.

The study is designed to evaluate the potential of NI-0501 as a targeted treatment for the disease with the objective of obtaining marketing authorization. NI-0501 is the first treatment specifically developed for HLH, a disease for which no drugs are currently approved. The study is currently underway at four investigational sites in the US and 14 sites in five European countries.

NI-0501 is a fully human monoclonal antibody that neutralizes interferon gamma, a cell-signaling protein believed to play a pivotal role in the development of HLH. In the ongoing Phase II study, NI-0501 was initially administered to patients showing unsatisfactory response or intolerance to conventional therapies including chemotherapy, immune-suppressive medicines, and immune-depleting drugs. The approved amendment to the protocol allows NI-0501 to be administered to patients as a first-line treatment before any other intervention.

HLH is a rare and sever disorder characterized by abnormal activation of the human immune system. The resulting inflammation rapidly attacks various parts of the body leading to multi-organ failure. The disease is fatal within a few weeks if left untreated and has a 40% to 50% mortality rate with current available treatments. HLH primarily affects infants and your children, but is becoming increasingly recognized in adults as the worldwide medical community becomes more familiar with its symptoms.

Treatment Period

The treatment regimen is divided into two phases:

• Treatment Period 1 is characterized by close monitoring during NI-0501 administrations, 6 infusions given every 3 days. In addition, patients will receive Dexamethasone for the duration of the treatment with the study therapy.
• Treatment Period 2 is characterized by less intense monitoring and includes 14 infusions, or less depending on the patient’s needs and conditions (Weeks 3 to 8). The time between NI- 0501 infusions can be increased; however this will not impact the safety assessments which will occur at least every 6 days.

All patients will be followed closely throughout the 8 weeks on study to test for response to treatment and to look for side effects of the medications with routine and other tests, such as physical examinations, blood tests, ECG and radiology tests.

Follow Up Period

All patients who have received at least one dose of NI-0501 will be monitored for 4 weeks after the last dose.

WHAT ARE THE BENEFITS?

You or your child may or may not receive direct benefit from participating in this study. There may be an improved chance of successfully treating your child’s HLH. Information learned in this study may benefit other patients with HLH in the future.

WILL I GET ALL THE FACTS ABOUT THE STUDY?

Parents and adult subjects will be given a consent form that thoroughly explains all of the details of the study. The consent form will cover all of the procedures, risks, benefits, compensation, who to contact with questions or concerns and more. A member of the study staff will review the consent form with you and answer your questions. Study procedures will not begin until the parent/guardian or you, the participating subject, have signed this consent form.

WHO SHOULD I CONTACT FOR MORE INFORMATION?

Sharon Mitchell
Cincinnati Children’s Hospital Medical Center
Cancer and Blood Diseases Institute
Blood and Marrow Transplantation and Immune Deficiencies

Phone: 513-636-4174
Sharon.Mitchell@cchmc.orgClick to Learn More

Country	Site #	Principal Investigator	Institute/Department	Address	Zip/City	Phone	Fax	Email
USA	16	Michael Jordan	Division of Immunobiology Department of Pediatrics Cincinnati Children’s Hospital	3333 Burnet Ave.	Cincinnati, OH 45229-3039	1-513-636-9461	1-513-803-1969	MichaelJordan@cchmc.org
USA	17	Carl Allen	Department of Pediatrics Section of Hematology-Oncology Baylor College of Medicine Texas Children’s Cancer Center	1102 Bates Street, Suite 750.01	Houston, TX 77030	1-832-824-4312	1-832-825-1206	ceallen@texaschildrens.org
USA	18	Jonathan Powell	Blood and Bone Marrow Transplantation Division of Pediatric Hematology Oncology Nemours Center for Cancer and Blood Disorders Alfred I. duPont Hospital for Children	1600 Rockland Road	Wilmington, DE 19803	1-302-651-5757	1-302-651-5760	JonathanPowell@nemours.org
USA	19	Barbara A Degar	Division of Pediatric Hematology/Oncology Dana-Farber Cancer Institute (DFCI)	44 Binney St.	Boston, MA 02215	1-617-632-5186	1-617-632-5710	BarbaraDegar@dfci.harvard.edu