Drug Trials Snapshots: OXERVATE
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to OXERVATE Prescribing Information for complete information.
OXERVATE (cenegermin-bkbj)
(ox'-er-vayt)
Dompé farmaceutici S.p.A.
Approval date: August 22, 2018
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
OXERVATE is used for the treatment of an eye condition called neurotrophic keratitis.
Neurotrophic keratitis is a rare disease of cornea (surface of the eye) characterized by the loss of sensation and by corneal wounds which are difficult to heal. It is caused by damage to the nerve which supplies sensation to the cornea.
How is this drug used?
One drop of OXERVATE is applied in the affected eye or both eyes if needed, 6 times each day, about 2 hours apart for eight weeks.
What are the benefits of this drug?
In the trials, more patients treated with OXERVATE drops achieved complete healing of corneal wounds in comparison to patients treated with placebo drops.
What are the benefits of this drug (results of trials used to assess efficacy)?
The figure below summarizes efficacy results for complete corneal healing defined as absence of staining of the corneal lesion and no persistent staining in the rest of the cornea after 8 weeks of treatment.
Table 2. Percentage of Patients with Complete Corneal Healing at Week 8
| Trial | OXERVATE | Vehicle | Treatment Difference* (95% CI) |
|---|---|---|---|
| Trial 1 | 15/23 (65.2%) | 4/24 (16.7%) | 48.6% (24%, 73.1%) |
| Trial 2 | 36/50 (72.0%) | 17/51 (33.3%) | 38.7% (20.7%, 56.6%) |
Patients without any post-baseline measurements were excluded from the analysis.
* p-value
OXERVATE Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: OXERVATE worked similarly in men and women.
- Race: The majority of the patients were White. The number of patients in other races was limited; therefore differences in response among races could not be determined.
- Age: OXERVATE worked similarly in patients above and below age 65.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Subgroup differences for sex, race and age in pooled trials are presented in the table below.
Table 3. Subgroup Analyses of the Complete Corneal Healing at Week 8 (Pooled ITT population; LOCF)
| Subgroup | OXERVATE (n/N, %) | Vehicle (n/N, %) | Difference (95% CI) |
|---|---|---|---|
| Sex | |||
| Male | 19/29 (65.5) | 5/25/ (20) | 45.5 (22.2,68.9) |
| Female | 32/44 (72.7) | 16/50 (32) | 40.7 (22.3,59.2) |
| Race | |||
| White | 46/69 (71) | 17/64 (26.6) | 44.5 (29.2, 59.7) |
| All other | 2/3 (66.7) | 0/6 (0) | 66.7 (13.3, 100) |
| Age | |||
| 16/23 (69.6) | 6/33 (18.2) | 51.4 (28.4, 74.3) | |
| ≥ 60 years | 35/50 (70) | 15/42 (35.7) | 34.3 (15, 53.6) |
Adapted from FDA Statistical review
What are the possible side effects?
The most common side effects are eye pain, eye redness, swelling (inflammation) of the eye, and increase of tears.
What are the possible side effects (results of trials used to assess safety)?
The most common adverse reaction was eye pain following instillation which was reported in approximately 16% of patients.
Other adverse reactions occurring in 1-10% of OXERVATE patients and more frequently than in the vehicle-treated patients included
- corneal deposits,
- foreign body sensation,
- ocular hyperemia,
- ocular inflammation and
- tearing.
OXERVATE Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in men and women.
- Race: The majority of patients in the trials were White. Differences in side effects among races could not be determined.
- Age: The occurrence of side effects was similar in patients above and below age 65.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes treatment emergent adverse events in treated subgroups for combined two trials.
Table 4. Adverse Events by Subgroups (safety population)
| Demographic Category | OXERVATE n/N (%) | Vehicle n/N (%) |
|---|---|---|
| Overall | 47/75 (63) | 38/76 (50) |
| Sex | ||
| Men | 21/31 (68) | 15/26 (58) |
| Women | 26/44 (59) | 23/50 (46) |
| Race | ||
| White | 43/71 (61) | 28/65 (43) |
| All Other* | 4/4 (100) | 10/11 (91) |
| Age | ||
| 65> | 24/38 (63) | 23/42 (55) |
| ≥65 years | 23/37 (62) | 15/34 (44) |
*Due to small number of patients in subgroups, all non-White patients are grouped together.
Clinical trial data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved OXERVATE based on evidence from two clinical trials of 151 patients with neurotrophic keratitis. The trials were conducted in the United States and Europe.
Figure below summarizes how many men and women were in the clinical trials.
Figure 1. Baseline Demographics by Sex (safety population)
Clinical trial data
Figure 2 and Table 1 summarize the percentage of patients by race in the clinical trials.
Figure 2. Baseline Demographics by Race (safety population)
Clinical trial data
Table 1. Demographics by Race
| Race | Number of Participants | Percentage |
|---|---|---|
| White | 136 | 90 |
| Black or African American | 5 | 3 |
| Asian | 2 | 1 |
| Native Hawaiian or Other Pacific Islander | 1 | less than 1 |
| Other | 1 | less than 1 |
| Not reported | 6 | 4 |
Clinical trial data
Figure 3. Baseline Demographics by Age (safety population)
Clinical trial data
Who participated in the trials?
The table below summarizes safety population in combined trials.
Table 5. Baseline Demographics (safety population)
| Demographic Category | OXERVATE (N=75) n (%) | Vehicle (N=76) n (%) | Total (N=151) n (%) |
|---|---|---|---|
| Sex | |||
| Men | 31 (41) | 26 (34) | 57 (38) |
| Women | 44 (59) | 50 (66) | 94 (62) |
| Race | |||
| White | 71 (95) | 65 (86) | 136 (90) |
| Black or African American | 2 (3) | 3 (4) | 5 (3) |
| All Other* | 2 (3) | 8 (10) | 10 (7) |
| Age (years) | |||
| Min, Max | 18, 95 | 23, 92 | 18, 95 |
| Age Group | |||
| 65> | 38 (51) | 42 (55) | 80 (53) |
| ≥65 years | 37 (49) | 34 (45) | 71 (47) |
| Ethnicity | |||
| Hispanic or Latino | 9 | 6 | 15 (10) |
| Not Hispanic or Latino | 61 | 60 | 121 (80) |
| Not reported | 5 | 10 | 15 (10) |
| Geographic Region | |||
| USA | 23(31) | 24 (32) | 47 (31) |
| Europe | 52 (69) | 52 (68) | 104 (69) |
*Includes 2 Asian, 1 Native Hawaiian or Other Pacific Islander, 1 Other and 6 patients with race not reported.
Clinical trial data
How were the trials designed?
The benefits and side effects of OXERVATE were evaluated in two clinical trials. Trials were similar in design with patients receiving either an OXERVATE or a placebo drops six times a day for eight weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.
The trials compared the improvement in corneal healing in both groups. The benefit was expressed as the percentage of patients who achieved complete corneal healing at the end of the treatment.
How were the trials designed?
The safety and efficacy of OXERVATE for the treatment of neurotropic keratitis were assessed in two randomized, vehicle-controlled, multi-center, double-masked trials. In one trial only patients with unilateral disease were treated, enrolled, while in the other one, patients with bilateral disease were treated bilaterally. Patients were randomized to OXERVATE or placebo in a 1:1 ratio. Treatment consisted of drop application 6 times daily in the affected eye(s) for 8 weeks.
Primary efficacy measure was complete corneal healing defined as absence of staining of the corneal lesion and no persistent staining in the rest of the cornea after 8 weeks of treatment.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.