Paroxysmal Nocturnal Hemoglobinuria (PNH)Phase 1/2NCT02352493
A Phase 1/2 Study of an Investigational Drug, ALN-CC5, in Healthy Adult Volunteers and Patients With PNH
A Phase 1/2 study testing ALN-CC5 and Sterile Normal Saline (0.9% NaCl) in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Alnylam Pharmaceuticals at 4 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-CC5 in healthy adult volunteers and subjects with PNH Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- What is being tested?
- ALN-CC5 and Sterile Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Jan 2015to Aug 2017
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adequate complete blood counts, liver and renal function
- 12-lead electrocardiogram (ECG) within normal limits
- Female subjects of child bearing potential agreeing to use a protocol specified method of contraception
- Male subjects agreeing to use protocol specified methods of contraception
- Willing to provide written informed consent and willing to comply with study requirements
Who cannot join
- Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk
- Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study
- History of multiple drug allergies or intolerance to subcutaneous injection
- Parts A and B of the study: Used prescription medications within 14 days or 7 half-lives of administration of the first dose of study drug.
- History of meningococcal infection
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United Kingdom3 sites
Clinical Trial Site
Leeds
Covance Clinical Research Unit
Leeds
Richmond Pharmacology
London
About this study
Official title: A Phase 1/2 Single-ascending and Multiple-ascending Dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN-CC5 in Healthy Adult Volunteers and Patients With Paroxysmal Nocturnal Hemoglobinuria
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-CC5 in healthy adult volunteers and subjects with PNH
- Being tested
- ALN-CC5, Sterile Normal Saline (0.9% NaCl)
- Keywords
- PNH, RNAi therapeutic
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-CC5Drug
Single or multiple doses of ALN-CC5 by subcutaneous (sc) injection
Sterile Normal Saline (0.9% NaCl)Drug
calculated volume to match active comparator
| Study group | Role | What they receive |
|---|---|---|
| ALN-CC5 | Active comparator | Not described Receives: Drug: ALN-CC5 |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Not described Receives: Drug: Sterile Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Adverse events were reported for single-ascending doses (SAD) or multiple ascending doses (MAD) of ALN-CC5 when administered to healthy adult subjects and of multiple doses (MD) in patients with paroxysmal nocturnal hemoglobinuria (PNH)
Measured: Part A: through day 658; Part B: through day 532; Part C: through day 280
Secondary outcomes (9)
Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Alternative Pathway (CAP)
Complement activity was measured in serum samples collected at timepoints throughout the study using the CAP ELISA assay. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in CAP from baseline.
Measured: Part A: through day 70; Part B: through day 140; Part C: through day 140
Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Classical Pathway (CCP)
Complement activity was measured in serum samples collected at time points throughout the study using the CCP ELISA assay. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in CCP from baseline.
Measured: Part A: through day 70; Part B: through day 140; Part C: through day 140
Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in C5 Protein Levels
Total C5 protein levels were measured in serum samples collected at time points throughout the study using a mass spectrometry-based method. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in C5 protein level from baseline.
Measured: Part A: through day 70; Part B: through day 140; Part C: through day 140
Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (25-mer)
Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 25-mer.
Measured: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84
Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (23-mer)
Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 23-mer.
Measured: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84
Pharmacokinetic (PK) Effect of ALN-CC5: T Max (25-mer)
Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 25-mer.
Measured: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84
Pharmacokinetic (PK) Effect of ALN-CC5: T Max (23-mer)
Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 23-mer.
Measured: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84
Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (25-mer)
Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 25-mer.
Measured: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84
Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (23-mer)
Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 23-mer.
Measured: Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2015 (estimated)
- Study startJan 2015
- Primary completionApr 2016
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Nocturnal Hemoglobinuria (PNH)Studies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nader Najafian, MD, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02352493
- Sponsor's protocol ID
- ALN-CC5-001
- Status last verified
- Mar 2020
- First submitted
- 23 Jan 2015
- Last updated
- 30 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ishigooka H, Katsumata H, Saiga K, Tokita D, Motoi S, Matsui C, Suzuki Y, Tomimatsu A, Nakatani T, Kuboi Y, Yamakawa T, Ikeda T, Ishii R, Imai T, Takagi T, Tanabe K. Novel Complement C5 Small-interfering RNA Lipid Nanoparticle Prolongs Graft Survival in a Hypersensitized Rat Kidney Transplant Model. Transplantation. 2022 Dec 1;106(12):2338-2347. doi: 10.1097/TP.0000000000004207. Epub 2022 Nov 22.
PubMed 35749284Badri P, Jiang X, Borodovsky A, Najafian N, Kim J, Clausen VA, Goel V, Habtemariam B, Robbie GJ. Pharmacokinetic and Pharmacodynamic Properties of Cemdisiran, an RNAi Therapeutic Targeting Complement Component 5, in Healthy Subjects and Patients with Paroxysmal Nocturnal Hemoglobinuria. Clin Pharmacokinet. 2021 Mar;60(3):365-378. doi: 10.1007/s40262-020-00940-9.
PubMed 33047216