An international study at different study sites providing a drug called cemdisiran (ALN-CC5) to patients with Atypical Hemolytic Uremic Syndrome by a subcutaneous injectio
- Conditions
- Atypical Hemolytic Uremic SyndromeMedDRA version: 20.0 Level: LLT Classification code 10019515 Term: Hemolytic uremic syndrome System Organ Class: 100000004851Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-001082-24-EE
- Lead Sponsor
- Alnylam Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 24
1. Willing to provide written informed consent and to comply with the study requirements
2. Age 18 years or older
3. Clinical presentation consistent with a diagnosis of primary aHUS
4. Clinical thrombotic microangiopathy (TMA) activity as defined by:
a. Evidence of low platelet count and
b. Evidence of hemolysis and
c. Evidence of impaired renal function
5. ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) >10% (at pre-Screening, Screening, or historically documented in their chart) in a plasma sample that was obtained prior to start of plasma therapy.
a. Patients who have already started plasma therapy and who do not have a documented pre-plasma ADAMTS13 result will not be eligible for the study unless they are proven to have a documented aHUS-associated mutation.
6. Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception
7. Vaccinated with meningococcal group ACWY conjugate vaccine and meningococcal group B vaccine or willingness to receive these vaccinations as well as prophylactic antibiotic treatment for at least 2 weeks after completing the recommended vaccination series or longer, if required by local standard of care.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
1. Abnormal liver function tests
2. Positive Shiga toxin producing Escherichia coli test
3. Suspected secondary aHUS, in the opinion of the Investigator, unless the patient has a documented aHUS-associated genetic mutation
4. Positive direct Coombs test
5. Prior eculizumab exposure within 3 months
6. Patients considered non-eculizumab responders. except for those with known C5 polymorphisms
7. Patients who have received hemodialysis for >3 months
8. Patients who require hemodialysis or plasma exchange more frequently than every 24 hours
9. Clinical laboratory test results or concomitant conditions considered clinically relevant and unacceptable in the opinion of the Investigator
10. Malignancy (except for non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years
11. Patients with active systemic bacterial or fungal infections, as demonstrated by a positive culture result, that require systemic treatment with antibiotics or antifungals
a. Patients receiving empiric or prophylactic antibiotics are not excluded
12. Patients with sepsis or a life-threatening infection
13. Received an investigational agent within the last 90 days or are in follow-up of another clinical study before the first ALN-CC5 administration
14. Active psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention
15. Bone marrow transplant recipients
16. Organ transplant recipients will be excluded, except for kidney transplant recipients with primary aHUS
a. For kidney transplant recipients, primary aHUS will be defined by known genetic mutation and no confounding diagnosis (eg, antibody-mediated rejection or viral infection) by routine kidney biopsy, as judged by the Investigator
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of ALN-CC5 on platelet response in adult patients with aHUS;<br> Secondary Objective: 1. To evaluate the effect of ALN-CC5 on hematological response<br> 2. To assess the effect of ALN-CC5 on thrombotic microangiopathy (TMA) response<br> 3. To assess the effect of ALN-CC5 on renal function parameters<br> 4. To evaluate the safety and tolerability of ALN-CC5<br> ;Primary end point(s): Proportion of patients with a platelet response at Week 32, with platelet response defined as platelet count =lower limit of normal (LLN) AND no rescue plasma therapy within the preceding 90 days;Timepoint(s) of evaluation of this end point: At week 32
- Secondary Outcome Measures
Name Time Method