An international study at different study sites providing a drug called cemdisiran (ALN-CC5) to patients with Atypical Hemolytic Uremic Syndrome by a subcutaneous injection

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2017-001082-24-EE
• Date of registration: 16/08/2017
• Prospective Registration: Yes
• Primary sponsor: Alnylam Pharmaceuticals, Inc.
• Public title: An international study at different study sites providing a drug called cemdisiran (ALN-CC5) to patients with Atypical Hemolytic Uremic Syndrome by a subcutaneous injection
• Scientific title: A Phase 2, Open Label, Multicenter Study of ALN-CC5 Administered Subcutaneously in Adult Patients with Atypical Hemolytic Uremic Syndrome
• Date of first enrolment: 15/09/2017
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001082-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Albania, Bosnia and Herzegovina, Canada, Estonia, Georgia, India, Latvia, Lithuania, Macedonia, the former Yugoslav Republic of, Moldova, Republic of, Romania, Serbia, Sweden

Contacts

• Name: Clinical Trials Hotline
• Affiliation: Alnylam Pharmaceuticals Inc

• Name: Clinical Trials Hotline
• Affiliation: Alnylam Pharmaceuticals Inc

Key inclusion & exclusion criteria

Inclusion criteria:
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

Exclusion criteria:
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Atypical Hemolytic Uremic Syndrome
MedDRA version: 20.0 Level: LLT Classification code 10019515 Term: Hemolytic uremic syndrome System Organ Class: 100000004851

Intervention(s)

Product Name: ALN-CC5
Product Code: ALN-CC5
Pharmaceutical Form: Solution for injection
INN or Proposed INN: cemdisiran
Current Sponsor code: ALN-62643
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

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

Secondary Objective: 1. To evaluate the effect of ALN-CC5 on hematological response
2. To assess the effect of ALN-CC5 on thrombotic microangiopathy (TMA) response
3. To assess the effect of ALN-CC5 on renal function parameters
4. To evaluate the safety and tolerability of ALN-CC5

Timepoint(s) of evaluation of this end point: At week 32

Main Objective: To evaluate the effect of ALN-CC5 on platelet response in adult patients with aHUS

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At week 32

Secondary end point(s): Proportion of patients with a hematological response at Week 32, with hematological response defined as the following:
- Platelet count =LLN, AND
- Lactate dehydrogenase (LDH) within the normal range, AND
- No rescue plasma therapy within the preceding 90 days
- Proportion of patients with LDH response at Week 32, with LDH response defined as LDH equal to or below the upper limit of normal (ULN) AND no rescue plasma therapy in the preceding 90 days
- Proportion of patients with a complete TMA response at Week 32, with a complete TMA response defined as the following:
- Hematological normalization (defined as platelet count =LLN and LDH within the normal range), AND
- Improvement in renal function as demonstrated by =25% decrease in serum creatinine from baseline, AND
- No rescue plasma therapy within the preceding 90 days
- Decrease in serum creatinine =25% from baseline, assessed over time
- Increase of estimated glomerular filtration rate (eGFR =15mL/min/1.73m2 from baseline, assessed over time
- Incidence, severity, and relatedness of adverse events (AEs)

Secondary ID(s)

2017-001082-24-LV

ALN-CC5-004

Source(s) of Monetary Support

Alnylam Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date:
Contact: