Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ALXN1910 in Healthy Participants
Research type
Research Study
Full title
A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of Subcutaneously and Intravenously Administered ALXN1910 in Healthy Adult Participants
IRAS ID
1004519
Contact name
Manjula Dundoo
Contact email
Sponsor organisation
Alexion Pharmaceuticals, Inc.
Eudract number
2021-005847-58
Clinicaltrials.gov Identifier
Research summary
Before a new medicine can be approved for use in patients, it is necessary to confirm that it is safe and effective. This is done by carrying out this, and possibly other research studies.
The clinical trial medicine does not yet have a name and it is not yet licensed. It is only known as ALXN1910.
Alexion Pharmaceuticals, Inc. is developing a clinical trial medicine for treating diseases where patients have weak bones due to poor bone mineralization (a condition where minerals do not get deposited in the bone to allow normal bone development). These diseases include hypophosphatasia (a disorder where decreased bone mineralization influences the development of bones and teeth), atypical femoral fracture (cracks in the thighbone that occur with little or no trauma to the bone) and neurofibromatosis type 1 (a genetic condition that causes tumours to grow along the nerves).
The clinical trial medicine works by increasing the activity of a specific enzyme (protein that controls how quickly chemical reactions occur in the body). By increasing this enzyme more bone mineralization occurs.
The main purpose of the clinical trial is to see how safe the clinical trial medicine is and how well it is tolerated after dosing.
The clinical trial will also investigate the following:
• Pharmacokinetics: How the clinical trial medicine is taken up, distributed throughout the body, chemically broken down, and eliminated from the body.
• Pharmacodynamics: How the body is affected by the clinical trial medicine, including if the body creates antibodies (a protein that is produced by the immune system to identify and destroy foreign substances) to the clinical trial medicine.
• If there is any difference in the pharmacokinetics and pharmacodynamics of ALXN1910 between Japanese and the other non-Japanese participants.
This is a first-time -in-human clinical trial, which means that this is the first time that the clinical trial medicine will be given to humans. Up to now, it has only been tested in animals and in the laboratory.
This trial will be conducted in PAREXEL Early Phase Unit, Northwick Park Hospital (Level 7), Harrow, UK. A total of 48 male and/or female participants (aged 18-55 years) will take part in this study.
In this clinical trial, participants will receive only one dose of the clinical trial medicine or placebo. A placebo is a “dummy treatment” that looks like the clinical trial medicine but has no active ingredients. The decision to receive clinical trial medicine or placebo will be made randomly (purely by chance, like the tossing of a coin), and neither participant nor the clinical team in the unit will know what each participant will receive. This particular design is known as ‘double blind’.
Japanese participants will receive a single dose of the clinical trial medication in the form of an injection given under the skin (subcutaneous). All other participants will receive a single dose of the clinical trial medication in the form of a subcutaneous injection or as an infusion into the vein of a participant’s arm (intravenous). An intravenous infusion is when the medication slowly drips into the vein over a set time period. The method in which the participants will receive the clinical trial medication will depend on which dosing group they are assigned to.Lay summary:
"In this study, participants received either ALXN1910 or placebo (a placebo looks like the treatment but has no active treatment ingredient in it). Each participant received a single dose of ALXN1910 or placebo given intravenously (IV, administered through a vein into the bloodstream) or subcutaneously (SC, administered under the skin). Participants were given “double-blind” ALXN1910 or placebo, meaning that neither the participants, caregivers, nor the study doctors knew which treatment was received. A computer selected whether a participant received ALXN1910 or placebo at random (by chance). A process called “3:1 randomization” stipulated that the number of participants receiving ALXN1910 was three times the number of participants receiving placebo.Participants were divided into 6 groups. Each group received a different dose of ALXN1910 or placebo as follows:
• Group 1 received 5 mg of ALXN1910 or placebo IV
• Group 2 received 15 mg of ALXN1910 or placebo SC
• Group 3 received 15 mg of ALXN1910 or placebo IV
• Group 4 (Japanese participants) received 15 mg of ALXN1910 or placebo SC
• Group 5 received 45 mg of ALXN1910 or placebo SC
• Group 6 received 135 mg of ALXN1910 or placebo SCParticipants in Group 4 were of Japanese origin only, because study doctors wanted to compare the effects of the drug to non-Japanese participants in the other groups. The Japanese participants in Group 4 were randomly assigned to receive either ALXN1910 or placebo and were given the same dose as participants in Group 2 (which included non-Japanese participants). Groups 1 and 2 received the assigned treatment consecutively. After completion of treatment in Group 2, Groups 3–5 received the assigned treatment at the same time. Study doctors reviewed safety data from participants in Groups 1 and 2 before starting treatment in participants in Groups 3 and 4. Study doctors also reviewed safety data in Groups 1, 2, and 5 before starting treatment in participants in Group 6.
A total of 48 participants (18 women + 30 men) took part in this study. Participants were between 18 and 55 years of age at the start of the study.
The study started in April 2022 and ended in February 2023.
The researchers wanted to see how safe ALXN1910 was in healthy adult participants by measuring the number of participants who experienced side effects during the treatment. Side effects and serious side effects were evaluated for up to 74 days after administration of ALXN1910.
Overall, 30 out of 48 participants (62.5%) experienced side effects during the study. Of those, 22 (61.1%) received ALXN1910, and 8 (66.7%) received placebo. All side effects were mild or moderate. Study doctors did not observe relevant differences in side effects between Japanese and non-Japanese participants. A total of 14 out of 48 participants (29.2%) had side effects that were thought by study doctors to be related to the treatment received. Of those, 10 received ALXN1910 (27.8%), and 4 received placebo (33.3%). One participant in Group 6 (who received the highest dose of ALXN1910) experienced loss of consciousness 36 days after treatment. Study doctors considered it a serious side effect related to the treatment received.
In summary, the information collected in this study showed that ALXN1910 was safe and well tolerated in healthy adults. All side effects were mild to moderate in intensity. The majority of side effects were thought by study doctors to be unrelated to ALXN1910. Side effects reported as being treatment-related occurred at a similar rate among participants receiving AXLN1910 and placebo. Study results also showed that ALXN1910 (SC, regardless of the dose) was slowly absorbed into the blood, peaked 3.5 to 4.5 days later, and stayed in the participants’ blood for 9 to 11 days. In addition, treatment with ALXN1910 lowered the concentrations of PPi and PLP in the blood."REC name
London - Riverside Research Ethics Committee
REC reference
22/LO/0003
Date of REC Opinion
11 Feb 2022
REC opinion
Further Information Favourable Opinion