Study of Ravulizumab in Pediatric Participants With HSCT-TMA

• Sponsor: Alexion Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04557735
• Collaborator: (none)
• Enrollment: 40
• Locations: 52
• Arm: 1
• Anticipated Duration (Months): 37.6
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab administered by intravenous infusion to pediatric participants, from 1 month to < 18 years of age, with HSCT-TMA. The treatment period is 26 weeks, followed by a 26-week off-treatment follow-up period.

Condition or Disease	Intervention/Treatment	Phase
Thrombotic Microangiopathy	Drug: Ravulizumab; Other: Best Supportive Care	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Open-label, Single Arm, Multicenter Study of Ravulizumab in Addition to Best Supportive Care in Pediatric Participants With Thrombotic Microangiopathy (TMA) After Hematopoietic Stem Cell Transplantation (HSCT)
• Actual Study Start Date: Nov 6, 2020
• Anticipated Primary Completion Date: Jun 28, 2023
• Anticipated Study Completion Date: Dec 26, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Ravulizumab plus Best Supportive Care Participants will receive ravulizumab plus Best Supportive Care as background therapy.

Drug: Ravulizumab; Weight-based doses of ravulizumab will be administered intravenously as a loading dose regimen followed by maintenance dosing every 4 or 8 weeks, depending upon weight.; Other Names: Ultomiris ; Other: Best Supportive Care; Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

Outcome Measures

Primary Outcome Measures

1. TMA Response [26 weeks (treatment period)]

Secondary Outcome Measures

1. Time To TMA Response [26 weeks (treatment period) and through 52 weeks (includes treatment period and off-treatment follow- up period)]

2. TMA Relapse [Follow Up period (183-365 Days after start of study medication)]

3. Overall Survival [26 weeks and 52 weeks]

4. Hematologic Response [26 weeks and 52 weeks]

   Hematologic Response as assessed by blood tests to measure lactate dehydrogenase (LDH) and platelet count. If baseline platelet count ≤ 50,000/mm3, all of the following criteria must be met: - Absolute platelet count > 50,000/mm3 without platelet transfusion support during the prior 7 days [or] If baseline platelet count > 50,000/mm3, all of the following criteria must be met: - ≥ 50% increase in platelet count compared to baseline value Normalization of LDH and absence of schistocytes

Eligibility Criteria

Criteria

• Ages Eligible for Study: 28 Days to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. ≥ 28 days of age up to < 18 years of age at the time of signing the informed consent.

2. Received HSCT within the past 12 months.

3. Diagnosis of TMA that persists for at least 72 hours despite initial management.

4. A TMA diagnosis based on meeting the select criteria during the Screening Period and/or <=14 days prior to the Screening Period.

5. Body weight ≥ 5 kilograms at Screening.

6. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception.

7. Participants must be vaccinated against meningococcal infections if clinically feasible. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis.

8. Participants or their legally authorized representative must be capable of giving signed informed consent or assent

Exclusion Criteria:

1. Thrombotic thrombocytopenic purpura (TTP) evidenced by ADAMTS13 deficiency.

2. Shiga toxin producing Escherichia coli infection.

3. Positive direct Coombs test

4. Clinical diagnosis of disseminated intravascular coagulation (DIC)

5. Known bone marrow/graft failure.

6. Diagnosis of veno-occlusive disease (VOD), regardless of severity.

7. Human immunodeficiency virus (HIV) infection

8. Unresolved meningococcal disease.

9. Presence or suspicion of sepsis (treated or untreated).

10. Pregnancy or breastfeeding.

11. Respiratory failure requiring mechanical ventilation

12. Previously or currently treated with a complement inhibitor

13. Participation in an interventional treatment study of any therapy for TMA

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Birmingham	Alabama	United States	35233
2	Clinical Trial Site	Phoenix	Arizona	United States	85016
3	Clinical Trial Site	Tucson	Arizona	United States	85724
4	Clinical Trial Site	Duarte	California	United States	91010
5	Clinical Trial Site	San Francisco	California	United States	94158
6	Clinical Trial Site	Aurora	Colorado	United States	80045
7	Clinical Trial Site	Atlanta	Georgia	United States	30322
8	Clinical Trial Site	Chicago	Illinois	United States	60611
9	Clinical Trial Site	Louisville	Kentucky	United States	40202
10	Clinical Trial Site	Minneapolis	Minnesota	United States	55414
11	Clinical Trial Site	Valhalla	New York	United States	10595
12	Clinical Trial Site	Charlotte	North Carolina	United States	28203
13	Clinical Trial Site	Akron	Ohio	United States	44308
14	Clinical Trial Site	Cleveland	Ohio	United States	44195
15	Clinical Trial Site	Portland	Oregon	United States	97239
16	Clinical Trial Site	Dallas	Texas	United States	75235
17	Clinical Trial Site	Fort Worth	Texas	United States	76104
18	Clinical Trial Site	Madison	Wisconsin	United States	53792
19	Clinical Trial Site	Bron		France
20	Clinical Trial Site	Nantes		France
21	Clinical Trial Site	Paris		France
22	Clinical Trial Site	Strasbourg		France
23	Clinical Trial Site	Vandœuvre-lès-Nancy		France
24	Clinical Trial Site	Jerusalem		Israel
25	Clinical Trial Site	Petach-Tikva		Israel
26	Clinical Trial Site	Ramat Gan		Israel
27	Clinical Trial Site	Bologna		Italy
28	Clinical Trial Site	Brescia		Italy
29	Clinical Trial Site	Firenze		Italy
30	Clinical Trial Site	Genova		Italy
31	Clinical Trial Site	Monza		Italy
32	Clinical Trial Site	Pavia		Italy
33	Clinical Trial Site	Rome		Italy
34	Clinical Trial Site	Torino		Italy
35	Clinical Trial Site	Verona		Italy
36	Clinical Trial Site	Fukuoka		Japan
37	Clinical Study Site	Fukushima		Japan
38	Clinical Trial Site	Kobe		Japan
39	Clinical Trial Site	Nagoya		Japan
40	Clinical Trial Site	Osakasayama		Japan
41	Clinical Trial Site	Osaka		Japan
42	Clinical Trial Site	Saitama		Japan
43	Clinical Trial Site	Setagaya-Ku		Japan
44	Clinical Trial Site	Goyang		Korea, Republic of
45	Clinical Trial Site	Seoul		Korea, Republic of
46	Clinical Trial Site	Barcelona		Spain
47	Clinical Trial Site	Esplugues De Llobregat		Spain
48	Clinical Trial Site	Madrid		Spain
49	Clinical Trial Site	Salamanca		Spain
50	Clinical Trial Site	Valencia		Spain
51	Clinical Trial Site	Bristol		United Kingdom
52	Clinical Trial Site	Leeds		United Kingdom

Sponsors and Collaborators

• Alexion Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04557735
• Other Study ID Numbers: ALXN1210-TMA-314; 2020-000761-16
• First Posted: Sep 22, 2020
• Last Update Posted: Aug 2, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alexion Pharmaceuticals: Thrombotic Microangiopathy (TMA); Ultomiris; Ravulizumab; Hematopoietic Stem Cell Transplant
• Additional relevant MeSH terms: Vascular Diseases; Thrombotic Microangiopathies; Ravulizumab

Study Results

No Results Posted as of Aug 2, 2022