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-LV
• Date of registration: 20/06/2017
• 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: 18/08/2017
• 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, 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 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%
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. Secondary aHUS
4. Positive direct Coombs test
5. Prior eculizumab exposure within 3 months
6. On dialysis for 3 months or longer
7. Transplant recipient
8. Patients considered non-eculizumab responders. except for those with known C5 polymorphisms
9. Patients who have received hemodialysis for >3 months
10. Patients who require hemodialysis or plasma exchange more frequently than every 24 hours
11. Clinical laboratory test results or concomitant conditions considered clinically relevant and unacceptable in the opinion of 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)

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

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

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.

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 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)

ALN-CC5-004

Source(s) of Monetary Support

Alnylam Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date:
Contact: